Defective AMPK regulation of cholesterol metabolism accelerates atherosclerosis by promoting HSPC mobilization and myelopoiesis

Journal article

Lee, Man K. S., Cooney, Olivia D., Lin, Xuzhu, Nadarajah, Shaktypreya, Dragoljevic, Dragana, Huynh, Kevin, Onda, Danise-Ann, Galic, Sandra, Meikle, Peter J., Edlund, Thomas, Fullerton, Morgan D., Kemp, Bruce E., Murphy, Andrew J. and Loh, Kim. (2022). Defective AMPK regulation of cholesterol metabolism accelerates atherosclerosis by promoting HSPC mobilization and myelopoiesis. Molecular Metabolism. 61, p. Article 101514. https://doi.org/10.1016/j.molmet.2022.101514

Publication dates
Authors	Lee, Man K. S., Cooney, Olivia D., Lin, Xuzhu, Nadarajah, Shaktypreya, Dragoljevic, Dragana, Huynh, Kevin, Onda, Danise-Ann, Galic, Sandra, Meikle, Peter J., Edlund, Thomas, Fullerton, Morgan D., Kemp, Bruce E., Murphy, Andrew J. and Loh, Kim
Abstract	Objectives Dysregulation of cholesterol metabolism in the liver and hematopoietic stem and progenitor cells (HSPCs) promotes atherosclerosis development. Previously, it has been shown that HMG-CoA-Reductase (HMGCR), the rate-limiting enzyme in the mevalonate pathway, can be phosphorylated and inactivated by the metabolic stress sensor AMP-activated protein kinase (AMPK). However, the physiological significance of AMPK regulation of HMGCR to atherogenesis has yet to be elucidated. The aim of this study was to determine the role of AMPK/HMGCR axis in the development of atherosclerosis. Methods We have generated a novel atherosclerotic-prone mouse model with defects in the AMPK regulation of HMGCR (Apoe−/−/Hmgcr KI mice). Atherosclerotic lesion size, plaque composition, immune cell and lipid profiles were assessed in Apoe−/− and Apoe−/−/Hmgcr KI mice. Results In this study, we showed that both male and female atherosclerotic-prone mice with a disruption of HMGCR regulation by AMPK (Apoe−/−/Hmgcr KI mice) display increased aortic lesion size concomitant with an increase in plaque-associated macrophages and lipid accumulation. Consistent with this, Apoe−/−/Hmgcr KI mice exhibited an increase in total circulating cholesterol and atherogenic monocytes, Ly6-Chi subset. Mechanistically, increased circulating atherogenic monocytes in Apoe−/−/Hmgcr KI mice was associated with enhanced egress of bone marrow HSPCs and extramedullary myelopoiesis, driven by a combination of elevated circulating 27-hydroxycholesterol and intracellular cholesterol in HSPCs. Conclusions Our results uncovered a novel signalling pathway involving AMPK-HMGCR axis in the regulation of cholesterol homeostasis in HSPCs, and that inhibition of this regulatory mechanism accelerates the development and progression of atherosclerosis. These findings provide a molecular basis to support the use of AMPK activators that currently undergoing Phase II clinical trial such as O–3O4 and PXL 770 for reducing atherosclerotic cardiovascular disease risks.
Keywords	AMPK; atherosclerosis; HMG-CoA reductase; cholesterol; HSPCs
Year	2022
Journal	Molecular Metabolism
Journal citation	61, p. Article 101514
Publisher	Elsevier GmbH
ISSN	2212-8778
Digital Object Identifier (DOI)	https://doi.org/10.1016/j.molmet.2022.101514
PubMed ID	35562083
Scopus EID	2-s2.0-85130393210
PubMed Central ID	PMC9124714
Open access	Published as ‘gold’ (paid) open access
Page range	1-12
Funder	National Health and Medical Research Council (NHMRC)
	National Heart Foundation of Australia
	L.E.W Carty Charitable Fund
	CSL
	Operational Infrastructure Support (OIS) Program, Victorian Government
Publisher's version	OA_Lee_2022_Defective_AMPK_regulation_of_cholesterol_metabolism.pdf License CC BY 4.0 File Access Level Open
Output status	Published
Online	10 May 2022
Publication process dates
Accepted	05 May 2022
Deposited	17 Mar 2023
Grant ID	1156634
	1085460
	1078752
	1085752
	1106154
	1142938
	100440

Permalink -

https://acuresearchbank.acu.edu.au/item/8ywy4/defective-ampk-regulation-of-cholesterol-metabolism-accelerates-atherosclerosis-by-promoting-hspc-mobilization-and-myelopoiesis

Download files

Publisher's version

	OA_Lee_2022_Defective_AMPK_regulation_of_cholesterol_metabolism.pdf
License: CC BY 4.0
File access level: Open

62
total views
76
total downloads
0
views this month
0
downloads this month

These values are for the period from 19th October 2020, when this repository was created.

Export as

Related outputs

The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury

Katerelos, Marina, Gleich, Kurt, Harley, Geoff, Loh, Kim, Oakhill, Jonathan, Kemp, Bruce Ernest, De Souza, David P., Narayana, Vinod K., Coughlan, Melinda T., Laskowski, Adrienne, Ling, Naomi, Murray-Segal, Lisa, Brink, Robert, Lee, Mardiana, Power, David and Mount, Peter. (2024). The AMPK activator ATX-304 alters cellular metabolism to protect against cisplatin-induced acute kidney injury. Biomedicine and Pharmacotherapy. 175, pp. 116730-116742. https://doi.org/10.1016/j.biopha.2024.116730

An AMPKa2-specific phospho-switch controls lysosomal targeting for activation

Morrison, Kaitlin R., Smiles, William J., Ling, Naomi X. Y., Hoque, Ashfaqul, Shea, Gabrielle, Ngoei, Kevin R. W., Yu, Dingyi, Murray-Segal, Lisa, Scott, John W., Galic, Sandra, Kemp, Bruce E., Petersen, Janni and Oakhill, Jonathan S.. (2022). An AMPKa2-specific phospho-switch controls lysosomal targeting for activation. Cell Reports. 38(7), p. Article 110365. https://doi.org/10.1016/j.celrep.2022.110365

Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis

Neopane, Katyayanee, Kozlov, Natalie, Negoita, Florentina, Murray-Segal, Lisa, Brink, Robert, Hoque, Ashfaqul, Ovens, Ashley J., Tjin, Gavin, McAloon, Luke M., Yu, Dingyi, Ling, Naomi X. Y., Sanders, Matthew J., Oakhill, Jonathan S., Scott, John W., Steinberg, Gregory R., Loh, Kim, Kemp, Bruce E., Sakamoto, Kei and Galic, Sandra. (2022). Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis. Cell Reports. 41(12), pp. 1-16. https://doi.org/10.1016/j.celrep.2022.111862

Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator

Ovens, Ashley J., Gee, Yi Sing, Ling, Naomi X. Y., Yu, Dingyi, Hardee, Justin P., Chung, Jin D., Ngoei, Kevin R. W., Waters, Nicholas J., Hoffman, Nolan J., Scott, John W., Loh, Kim, Spengler, Katrin, Heller, Regine, Parker, Michael W., Lynch, Gordon S., Huang, Fei, Galic, Sandra, Kemp, Bruce E., Baell, Jonathan B., ... Langendorf, Christopher G.. (2022). Structure-function analysis of the AMPK activator SC4 and identification of a potent pan AMPK activator. Biochemical Journal. 479(11), pp. 1181-1204. https://doi.org/10.1042/BCJ20220067

Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism

Stork, Britanny A., Dean, Adam, Ortiz, Andrea R., Saha, Pradip, Putluri, Nagireddy, Planas-Silva, Maricarmen D., Mahmud, Iqbal, Rajapakshe, Kimal, Coarfa, Cristian, Knapp, Stefan, Lorenzi, Philip L., Kemp, Bruce E., Turk, Benjamin E., Scott, John W., Means, Anthony R. and York, Brian. (2022). Calcium/calmodulin-dependent protein kinase kinase 2 regulates hepatic fuel metabolism. Molecular Metabolism. 62, p. Article 101513. https://doi.org/10.1016/j.molmet.2022.101513

Disrupting AMPK-glycogen binding in mice increases carbohydrate utilization and reduces exercise capacity

Janzen, Natalie R., Whitfield, Jamie, Murray-Segal, Lisa, Kemp, Bruce E., Hawley, John A. and Hoffman, Nolan J.. (2022). Disrupting AMPK-glycogen binding in mice increases carbohydrate utilization and reduces exercise capacity. Frontiers in Physiology. 13, p. 859246. https://doi.org/10.3389/fphys.2022.859246

Blocking AMPK signalling to acetyl-CoA carboxylase increases cisplatin-induced acute kidney injury and suppresses the benefit of metformin

Harley, Geoff, Katerelos, Marina, Gleich, Kurt, de Souza, David P., Narayana, Vinod K., Kemp, Bruce E., Power, David A. and Mount, Peter F.. (2022). Blocking AMPK signalling to acetyl-CoA carboxylase increases cisplatin-induced acute kidney injury and suppresses the benefit of metformin. Biomedicine and Pharmacotherapy. 153, p. Article 113377. https://doi.org/10.1016/j.biopha.2022.113377

AMPK activation by SC4 inhibits noradrenaline-induced lipolysis and insulin-stimulated lipogenesis in white adipose tissue

Chuang, Sheng-Ju, Johanns, Manuel, dit Ruys, Sébastien, Steinberg, Gregory R., Kemp, Bruce Ernest E., Viollet, Benoit and Rider, Mark. (2022). AMPK activation by SC4 inhibits noradrenaline-induced lipolysis and insulin-stimulated lipogenesis in white adipose tissue. Biochemical Journal. 478(21), pp. 3869-3889. https://doi.org/10.1042/BCJ20210411

Post-translational modifications of the energy guardian AMP-activated protein kinase

Ovens, Ashley J., Scott, John W., Langendorf, Christopher G., Kemp, Bruce E., Oakhill, Jonathan S. and Smiles, William J.. (2021). Post-translational modifications of the energy guardian AMP-activated protein kinase. International Journal of Molecular Sciences. 22(3), p. Article 1229. https://doi.org/10.3390/ijms22031229

Cellular bioenergetics and AMPK and TORC1 signalling in blood lymphoblasts are biomarkers of clinical status in FMR1 premutation carriers

Loesch, Danuta Z., Kemp, Bruce E., Bui, Minh Q., Fisher, Paul R., Allan, Claire Y., Sanislav, Oana, Ngoel, Kevin R. W., Atkinson, Anna, Tassone, Flora, Annesley, Sarah J. and Storey, Elsdon. (2021). Cellular bioenergetics and AMPK and TORC1 signalling in blood lymphoblasts are biomarkers of clinical status in FMR1 premutation carriers. Frontiers in Psychiatry. 12, p. Article 747268. https://doi.org/10.3389/fpsyt.2021.747268

Relationships between mitochondrial function, AMPK, and TORC1 signaling in lymphoblasts with premutation alleles of the FMR1 gene

Fisher, Paul R., Allan, Claire Y., Sanislav, Oana, Atkinson, Anna, Ngoei, Kevin R. W., Kemp, Bruce E., Storey, Elsdon, Loesch, Danuta Z. and Annesley, Sarah J.. (2021). Relationships between mitochondrial function, AMPK, and TORC1 signaling in lymphoblasts with premutation alleles of the FMR1 gene. International Journal of Molecular Sciences. 22(19), p. Article 10393. https://doi.org/10.3390/ijms221910393

Mice with whole-body disruption of AMPK-glycogen binding have increased adiposity, reduced fat oxidation and altered tissue glycogen dynamics

Janzen, Natalie, Whitfield, Jamie, Murray-Segal, Lisa, Kemp, Bruce E., Hawley, John A. and Hoffman, Nolan J.. (2021). Mice with whole-body disruption of AMPK-glycogen binding have increased adiposity, reduced fat oxidation and altered tissue glycogen dynamics. International Journal of Molecular Sciences. 22(17), p. Article: 9616. https://doi.org/10.3390/ijms22179616

Salsalate reduces atherosclerosis through AMPKβ1 in mice

Day, Emily A., Ford, Rebecca J., Smith, Brennan K., Houde, Vanessa P., Stypa, Stephanie, Rehal, Sonia, Lhotak, Sarka, Kemp, Bruce E., Trigatti, Bernardo L., Werstuck, Geoff H., Austin, Richard C., Fullerton, Morgan D. and Steinberg, Gregory R.. (2021). Salsalate reduces atherosclerosis through AMPKβ1 in mice. Molecular Metabolism. 53, p. Article: 101321. https://doi.org/10.1016/j.molmet.2021.101321

Voluntary physical activity protects against olanzapine-induced hyperglycemia

Shamshoum, Hesham, McKie, Greg L., Medak, Kyle D., Ashworth, Kristen E., Kemp, Bruce E. and Wright, David C.. (2021). Voluntary physical activity protects against olanzapine-induced hyperglycemia. Journal of Applied Physiology. 130(2), pp. 466-478. https://doi.org/10.1152/japplphysiol.00876.2020

AMPK mediates energetic stress-induced liver GDF15

Townsend, Logan K., Weber, Alyssa J., Day, Emily A., Shamshoum, Hesham, Shaw, Simon J., Perry, Christopher G. R., Kemp, Bruce E., Steinberg, Gregory R. and Wright, David C.. (2020). AMPK mediates energetic stress-induced liver GDF15. The FASEB Journal. 35(1), p. e21218. https://doi.org/10.1096/fj.202000954R

Foam cell induction activates ampk but uncouples its regulation of autophagy and lysosomal homeostasis

LeBlond, Nicholas D., Nunes, Julia R. C., Smith, Tyler K. T., O’Dwyer, Conor, Robichaud, Sabrina, Gadde, Suresh, Côté, Marceline, Kemp, Bruce E., Ouimet, Mireille and Fullerton, Morgan D.. (2020). Foam cell induction activates ampk but uncouples its regulation of autophagy and lysosomal homeostasis. International Journal of Molecular Sciences. 21(23), pp. 1-21. https://doi.org/10.3390/ijms21239033

Functional analysis of an R311C variant of Ca2+-calmodulin-dependent protein kinase kinase-2 (CaMKK2) found as a de novo mutation in a patient with bipolar disorder

Xy Ling, Naomi, Langendorf, Christopher G., Hoque, Ashfaqul, Galic, Sandra, Loh, Kim, Kemp, Bruce E., Gundlach, Andrew L., Oakhill, Jonathan S. and Scott, John W.. (2020). Functional analysis of an R311C variant of Ca2+-calmodulin-dependent protein kinase kinase-2 (CaMKK2) found as a de novo mutation in a patient with bipolar disorder. Bipolar Disorders. 22(8), pp. 841-848. https://doi.org/10.1111/bdi.12901

CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins

Langendorf, Christopher G., O'Brien, Matthew T., Ngoei, Kevin R. W., McAloon, Luke M., Dhagat, Urmi, Hoque, Ashfaqul, Ling, Naomi X. Y., Dite, Toby A., Galic, Sandra, Loh, Kim, Parker, Michael W., Oakhill, Jonathan S., Kemp, Bruce E. and Scott, John W.. (2020). CaMKK2 is inactivated by cAMP-PKA signaling and 14-3-3 adaptor proteins. Journal of Biological Chemistry. 295(48), pp. 16239-16250. https://doi.org/10.1074/jbc.RA120.013756

The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKa2

Lee, Jung Ok, Byun, Won Seok, Kang, Min Ju, Han, Jeong Ah, Moon, Jiyoung, Shin, Min-Jeong, Lee, Ho Jun, Chung, Ji Hyung, Lee, Jin-Seok, Son, Chang-Gue, Song, Kwon-Ho, Kim, Tae Woo, Lee, Eun-Soo, Kim, Hong Min, Chung, Choon Hee, Ngoei, Kevin R. W., Ling, Naomi X. Y., Oakhill, Jonathan S., Galic, Sandra, ... Kim, Hyeon Soo. (2020). The myokine meteorin-like (metrnl) improves glucose tolerance in both skeletal muscle cells and mice by targeting AMPKa2. The FEBS Journal. 287(10), pp. 2087-2104. https://doi.org/10.1111/FEBS.15301

Genetic loss of AMPK-glycogen binding destabilizes AMPK and disrupts metabolism

Hoffman, Nolan J., Whitfield, Jamie, Janzen, Natalie R., Belhaj, Mehdi R., Galic, Sandra, Murray-Segal, Lisa, Smiles, William J., Ling, Naomi X. Y., Dite, Toby A., Scott, John W., Oakhill, Jonathan S., Brink, Robert, Kemp, Bruce E. and Hawley, John A.. (2020). Genetic loss of AMPK-glycogen binding destabilizes AMPK and disrupts metabolism. Molecular Metabolism. 41, pp. 1-13. https://doi.org/10.1016/j.molmet.2020.101048

Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK β1 isoforms

Pinkosky, Stephen L., Scott, John W., Desjardins, Eric M., Smith, Brennan K., Day, Emily A., Ford, Rebecca J., Langendorf, Christopher G., Ling, Naomi X. Y., Nero, Tracy L., Loh, Kim, Galic, Sandra, Hoque, Ashfaqul, Smiles, William J., Ngoei, Kevin R. W., Parker, Michael W., Yan, Yan, Melcher, Karsten, Kemp, Bruce E., Oakhill, Jonathan S. and Steinberg, Gregory R.. (2020). Long-chain fatty acyl-CoA esters regulate metabolism via allosteric control of AMPK β1 isoforms. Nature Metabolism. 2(9), pp. 873-881. https://doi.org/10.1038/s42255-020-0245-2

Effects of PKB/Akt inhibitors on insulin-stimulated lipogenesis and phosphorylation state of lipogenic enzymes in white adipose tissue

Hussain, Nusrat, Chuang, Sheng-Ju, Johanns, Manuel, Vertommen, Didier, Steinberg, Gregory R., Kemp, Bruce E. and Rider, Mark H.. (2020). Effects of PKB/Akt inhibitors on insulin-stimulated lipogenesis and phosphorylation state of lipogenic enzymes in white adipose tissue. Biochemical Journal. 477(8), pp. 1373-1389. https://doi.org/10.1042/BCJ20190788

AMPK β1 activation suppresses antipsychotic-induced hyperglycemia in mice

Shamshoum, Hesham, Medak, Kyle D., Townsend, Logan K., Ashworth, Kristen E., Bush, Natasha D., Halm, Margaret K., Kemp, Bruce E. and Wright, David C.. (2019). AMPK β1 activation suppresses antipsychotic-induced hyperglycemia in mice. The FASEB Journal. 33(12), pp. 14010-14021. https://doi.org/10.1096/fj.201901820R

ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways

Lee, Hye Jeong, Moon, Jiyoung, Chung, InHyeok, Chung, Ji Hyung, Park, Chan, Lee, Jung Ok, Han, Jeong Ah, Kang, Min Ju, Yoo, Eun Hye, Kwak, So-Young, Jo, Garam, Park, Wonil, Park, Jonghoon, Kim, Kyoung Min, Lim, Soo, Ngoei, Kevin R. W., Ling, Naomi X. Y., Oakhill, Jonathan S., Galic, Sandra, ... Kim, Hyeon Soo. (2019). ATP synthase inhibitory factor 1 (IF1), a novel myokine, regulates glucose metabolism by AMPK and Akt dual pathways. The FASEB Journal. 33(12), pp. 14825 - 14840. https://doi.org/10.1096/fj.201901440RR

Absence of the β1 subunit of AMP-activated protein kinase reduces myofibroblast infiltration of the kidneys in early diabetes

Choy, Suet-Wan, Fraser, Scott A., Katerelos, Marina, Galic, Sandra, Kemp, Bruce E., Mount, Peter F. and Power, David A.. (2019). Absence of the β1 subunit of AMP-activated protein kinase reduces myofibroblast infiltration of the kidneys in early diabetes. International Journal of Experimental Pathology. 100(2), pp. 114 - 122. https://doi.org/10.1111/iep.12313

Inhibition of adenosine monophosphate-activated protein kinase-3-hydroxy-3-methylglutaryl coenzyme a reductase signaling leads to hypercholesterolemia and promotes hepatic steatosis and insulin resistance

Loh, Kim, Tam, Shanna, Murray-Segal, Lisa, Huynh, Kevin, Meikle, Peter J., Scott, John W., van Denderen, Bryce J., Chen, Zhiping, Steel, Rohan, LeBlond, Nicholas D., Burkovsky, Leah A., O'Dwyer, Conor, Nunes, Julia R. C., Steinberg, Gregory R., Fullerton, Morgan D., Galic, Sandra and Kemp, Bruce E.. (2019). Inhibition of adenosine monophosphate-activated protein kinase-3-hydroxy-3-methylglutaryl coenzyme a reductase signaling leads to hypercholesterolemia and promotes hepatic steatosis and insulin resistance. Hepatology Communications. 3(1), pp. 84 - 98. https://doi.org/10.1002/hep4.1279

Phosphorylation of Acetyl-CoA Carboxylase by AMPK reduces renal fibrosis and is essential for the anti-fibrotic effect of metformin

Lee, Mardiana, Kateleros, Marina, Gleich, Kurt, Galic, Sandra, Kemp, Bruce, Mount, Peter F. and Power, David A.. (2018). Phosphorylation of Acetyl-CoA Carboxylase by AMPK reduces renal fibrosis and is essential for the anti-fibrotic effect of metformin. Journal of the American Society of Nephrology. 29(9), pp. 2326 - 2336. https://doi.org/10.1681/ASN.2018010050

Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice

Wali, Jibran A., Galic, Sandra, Tan, Christina Y. R., Gurzov, Esteban N., Frazier, Ann E., Connor, Timothy, Ge, Jingjing, Pappas, Evan G., Stroud, David, Varanasi, L. Chitra, Selck, Claudia, Ryan, Michael T., Thorburn, David R., Kemp, Bruce, Krishnamurthy, Balasubramanian, Kay, Thomas W. H., McGee, S. L. and Thomas, Helen. (2018). Loss of BIM increases mitochondrial oxygen consumption and lipid oxidation, reduces adiposity and improves insulin sensitivity in mice. Cell Death and Differentiation. 25(1), pp. 217 - 225. https://doi.org/10.1038/cdd.2017.168

AMPK signaling to acetyl-CoA carboxylase is required for fasting - and cold-induced appetite but not thermogenesis

Galic, Sandra, Loh, Kim, Murray-Segal, Lisa, Steinberg, Gregory R., Andrews, Zane B. and Kemp, Bruce. (2018). AMPK signaling to acetyl-CoA carboxylase is required for fasting - and cold-induced appetite but not thermogenesis. eLife. 7, pp. 1 - 22. https://doi.org/10.7554/eLife.32656

Structural determinants for small-molecule activation of skeletal muscle AMPK α2β2γ1 by the glucose importagog sc4

Ngoei, Kevin R.W., Langendorf, Christopher G., Ling, Naomi, Hoque, Ashfaqul, Johnson, Swapna, Camerino, Michelle C., Walker, Scott R., Bozikis, Ylva E., Dite, Toby A., Ovens, Ashley J., Smiles, William, Jacobs, Roxane, Huang, He, Parker, Michael W., Scott, John W., Rider, Mark H., Foitzik, Richard C., Kemp, Bruce, Baell, Jonathan B. and Oakhill, Jonathan S.. (2018). Structural determinants for small-molecule activation of skeletal muscle AMPK α2β2γ1 by the glucose importagog sc4. Cell Chemical Biology. 25(6), pp. 728 - 737. https://doi.org/10.1016/j.chembiol.2018.03.008

AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation

Lepropre, Sophie, Kautbally, Shakeel, Octave, Marie, Ginion, Audrey, Onselaer, Marie-Blanche, Steinberg, Gregory R., Kemp, Bruce E., Hego, Alexandre, Wéra, Odile, Brouns, Sanne, Swieringa, Frauke, Giera, Martin, Darley-Usmar, Victor M., Ambroise, Jérôme, Guigas, Bruno, Heemskerk, Johan, Bertrand, Luc, Oury, Cécile, Beauloye, Christophe and Horman, Sandrine. (2018). AMPK-ACC signaling modulates platelet phospholipids and potentiates thrombus formation. Blood. 132(11), pp. 1180 - 1192. https://doi.org/10.1182/blood-2018-02-831503

The spectrum of neurological and white matter changes and premutation status categories of older male carriers of the FMR1 alleles are linked to genetic (CGG and FMR1 mRNA) and cellular stress (AMPK) markers

Loesch, Danuta Z., Trost, Nicholas, Bui, Minh Q., Hammersley, Eleanor, Lay, Sui T., Annesley, Sarah J., Sanislav, Oana, Allan, Claire Y., Tassone, Flora, Chen, Zhi-Ping, Ngoei, Kevin R. W., Kemp, Bruce E., Francis, David, Fisher, Paul R. and Storey, Elsdon. (2018). The spectrum of neurological and white matter changes and premutation status categories of older male carriers of the FMR1 alleles are linked to genetic (CGG and FMR1 mRNA) and cellular stress (AMPK) markers. Frontiers in Genetics. 9, pp. 1 - 12. https://doi.org/10.3389/fgene.2018.00531

Visualizing AMPK drug binding sites through crystallization of full-length phosphorylated α2β1γ1 heterotrimer

Langendorf, Christopher G., Oakhill, Jonathan S. and Kemp, Bruce E.. (2018). Visualizing AMPK drug binding sites through crystallization of full-length phosphorylated α2β1γ1 heterotrimer. In In D. Neumann and B. Viollet (Ed.). AMPK: Methods and protocol pp. 15 - 27 Humana Press, Inc.. https://doi.org/10.1007/978-1-4939-7598-3_2

Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells

Hoque, Ashfaqul, Sivakumaran, Priyadharshini, Bond, Simon T., Ling, Naomi, Kong, Anne M., Scott, John W., Bandara, Nadeeka, Hernandez, Damian, Liu, Guei-Sheung, Wong, Raymond, Ryan, Michael T., Hausenloy, Derek, Kemp, Bruce, Oakhill, Jonathan S., Drew, Brian, Pebay, Alice and Lim, Shiang Y.. (2018). Mitochondrial fission protein Drp1 inhibition promotes cardiac mesodermal differentiation of human pluripotent stem cells. Cell Death Discovery. 4(39), pp. 1 - 13. https://doi.org/10.1038/s41420-018-0042-9

AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965

Dite, Toby A., Langendorf, Christopher, Hoque, Ashfaqul, Galic, Sandra, Rebello, Richard J., Ovens, Ashley J., Lindqvist, Lisa M., Ngoei, Kevin R.W., Ling, Naomi, Furic, Luc, Kemp, Bruce, Scott, John W. and Oakhill, Jonathan S.. (2018). AMP-activated protein kinase selectively inhibited by the type II inhibitor SBI-0206965. Journal of Biological Chemistry. 293(23), pp. 8874 - 8885. https://doi.org/10.1074/jbc.RA118.003547

Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo

Madiraju, Anila K., Qiu, Yang, Perry, Rachel J., Rahimi, Yasmeen, Zhang, Xian-Man, Zhang, Dongyan, Camporez, João-Paulo G., Cline, Gary W., Butrico, Gina M., Kemp, Bruce, Casals, Gregori, Steinberg, Gregory R., Vatner, Daniel F., Petersen, Kitt F. and Shulman, Gerald I.. (2018). Metformin inhibits gluconeogenesis via a redox-dependent mechanism in vivo. Nature Medicine. 24(9), pp. 1384-1394. https://doi.org/10.1038/s41591-018-0125-4

Impact of genetic variation on human CaMKK2 regulation by Ca2+ -calmodulin and multisite phosphorylation

O'Brien, Matthew, Oakhill, Jonathan S., Ling, Naomi, Langendorf, Christopher G., Hoque, Ashfaqul, Dite, Toby A., Means, Anthony R., Kemp, Bruce and Scott, John W.. (2017). Impact of genetic variation on human CaMKK2 regulation by Ca2+ -calmodulin and multisite phosphorylation. Scientific Reports. 7, pp. 1 - 11. https://doi.org/10.1038/srep43264

AMPK ß1 reduces tumor progression and improves survival in p53 null mice

Houde, Vanessa P., Donzelli, Sara, Sacconi, Andrea, Galic, Sandra, Hammill, Joanne A., Bramson, Jonathan L., Foster, Robert A., Tsakiridis, Theodoros, Kemp, Bruce, Grasso, Giuseppe, Blandino, Giovanni, Muti, Paola and Steinberg, Gregory R.. (2017). AMPK ß1 reduces tumor progression and improves survival in p53 null mice. Molecular Oncology. 11(9), pp. 1143 - 1155. https://doi.org/10.1002/1878-0261.12079

The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs

Dite, Toby A., Ling, Naomi, Scott, John W., Hoque, Ashfaqul, Galic, Sandra, Parker, Benjamin L., Ngoei, Kevin R.W., Langendorf, Christopher G., O'Brien, Matthew, Kundu, Mondira, Viollet, Benoit, Steinberg, Gregory R., Sakamoto, Kei, Kemp, Bruce and Oakhill, Jonathan S.. (2017). The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs. Nature Communications. 8(571), pp. 1 - 14. https://doi.org/10.1038/s41467-017-00628-y

Metabolism: Energy sensing through a sugar diphosphate

Kemp, Bruce and Oakhill, Jonathan S.. (2017). Metabolism: Energy sensing through a sugar diphosphate. Nature. 548(7665), pp. 36 - 37. https://doi.org/10.1038/nature23099

Fake inhibitors: AMPK activation trumps inhibition

Langendorf, Christopher G., Scott, John W. and Kemp, Bruce E.. (2017). Fake inhibitors: AMPK activation trumps inhibition. Cell Chemical Biology. 24(7), pp. 775 - 777. https://doi.org/10.1016/j.chembiol.2017.07.005

Metformin prevents nigrostriatal dopamine degeneration independent of AMPK activation in dopamine neurons

Bayliss, Jacqueline A., Lemus, Moyra B., Santos, Vanessa, Deo, Minh, Davies, Jeffrey S., Kemp, Bruce Ernest, Elsworth, John D. and Andrews, Zane B.. (2016). Metformin prevents nigrostriatal dopamine degeneration independent of AMPK activation in dopamine neurons. PLoS ONE. 11(7), pp. 1 - 15. https://doi.org/10.1371/journal.pone.0159381

Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding

Langendorf, Christopher G., Ngoei, Kevin R. W., Scott, John W., Ling, Naomi X. Y., Issa, Sam M. A., Gorman, Michael A., Parker, Michael W., Sakamoto, Kei, Oakhill, Jonathan S. and Kemp, Bruce Ernest. (2016). Structural basis of allosteric and synergistic activation of AMPK by furan-2-phosphonic derivative C2 binding. Nature Communications. 7, pp. 1 - 8. https://doi.org/10.1038/ncomms10912

Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity

Annesley, Sarah J., Lay, Sui T., De Piazza, Shawn W., Sanislav, Oana, Hammersley, Eleanor, Allan, Claire Y., Francione, Lisa M., Bui, Minh Q., Chen, Zhi-Ping, Ngoei, Kevin R. W., Tassone, Flora, Kemp, Bruce E., Storey, Elsdon, Evans, Andrew, Loesch, Danuta Z. and Fisher, Paul R.. (2016). Immortalized Parkinson's disease lymphocytes have enhanced mitochondrial respiratory activity. Disease Models and Mechanisms. 9(9), pp. 1295 - 1305. https://doi.org/10.1242/dmm.025684

Ghrelin-AMPK signaling mediates the neuroprotective effects of calorie restriction in Parkinson's Disease

Bayliss, Jacqueline A., Lemus, Moyra B., Stark, Romana, Santos, Vanessa V., Thompson, Aiysha, Rees, Daniel J., Galic, Sandra, Elsworth, John D., Kemp, Bruce Ernest, Davies, Jeffrey S. and Andrews, Zane B.. (2016). Ghrelin-AMPK signaling mediates the neuroprotective effects of calorie restriction in Parkinson's Disease. Journal of Neuroscience. 36(10), pp. 3049 - 3063. https://doi.org/10.1523/JNEUROSCI.4373-15.2016

Skeletal muscle AMPK is essential for the maintenance of FNDC5 expression

Lally, James S. V., Ford, Rebecca J., Johar, Jasper, Crane, Justin D., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2015). Skeletal muscle AMPK is essential for the maintenance of FNDC5 expression. Physiological Reports. 3(5), pp. 1 - 9. https://doi.org/10.14814/phy2.12343

Salicylate improves macrophage cholesterol homeostasis via activation of Ampk

Fullerton, Morgan D., Ford, Rebecca J., McGregor, Chelsea P., LeBlond, Nicholas D., Snider, Shayne A., Stypa, Stephanie A., Day, Emily A., Lhoták, Šárka, Schertzer, Jonathan D., Austin, Richard C., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2015). Salicylate improves macrophage cholesterol homeostasis via activation of Ampk. Journal of Lipid Research. 56(5), pp. 1025 - 1033. https://doi.org/10.1194/jlr.M058875

Choreography of AMPK activation

Langerdorf, Christopher G. and Kemp, Bruce Ernest. (2015). Choreography of AMPK activation. Cell Research. 25(1), pp. 5 - 6. https://doi.org/10.1038/cr.2014.163

Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise

O'Neill, Hayley M., Lally, James S., Galic, Sandra, Pulinilkunnil, Thomas, Ford, Rebecca J., Dyck, Jason R. B., Van Denderen, Bryce J,, Kemp, Bruce Ernest and Steinberg, Gregory R.. (2015). Skeletal muscle ACC2 S212 phosphorylation is not required for the control of fatty acid oxidation during exercise. Physiological Reports. 3(7), pp. 1 - 10. https://doi.org/10.14814/phy2.12444

Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity

Ford, Rebecca, Fullerton, Morgan, Pinkosky, Stephen, Day, Emily, Scott, John, Oakhill, Jonathan, Bujak, Adam, Smith, Brennan, Crane, Justin, Blumer, Regje, Marcinko, Katarina, Kemp, Bruce, Gerstein, Hertzel and Steinberg, Gregory. (2015). Metformin and salicylate synergistically activate liver AMPK, inhibit lipogenesis and improve insulin sensitivity. Biochemical Journal. 468(1), pp. 125 - 132. https://doi.org/10.1042/BJ20150125

High intensity interval training improves liver and adipose tissue insulin sensitivity

Marcinko, Katarina, Sikkema, Sarah R., Samaan, M. Constantine, Kemp, Bruce Ernest, Fullerton, Morgan D. and Steinberg, Gregory R.. (2015). High intensity interval training improves liver and adipose tissue insulin sensitivity. Molecular Metabolism. 4(12), pp. 903 - 915. https://doi.org/10.1016/j.molmet.2015.09.006

Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release

Scott, John, Galic, Sandra, Graham, Kate, Foitzik, Richard, Ling, Naomi, Dite, Toby, Issa, Samah, Langendorf, Chris, Weng, Qing, Thomas, Helen, Kay, Thomas, Birnberg, Neal, Steinberg, Gregory, Kemp, Bruce and Oakhill, Jonathan. (2015). Inhibition of AMP-activated protein kinase at the allosteric drug-binding site promotes islet insulin release. Chemistry and Biology. 22(6), pp. 705 - 711. https://doi.org/10.1016/j.chembiol.2015.05.011

AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism

Sung, Miranda M., Zordoky, Beshay N. M., Bujak, Adam L., Lally, James S. V., Fung, David, Young, Martin E., Horman, Sandrine, Miller, Edward J., Light, Peter E., Kemp, Bruce Ernest, Steinberg, Gregory R. and Dyck, Jason R. B.. (2015). AMPK deficiency in cardiac muscle results in dilated cardiomyopathy in the absence of changes in energy metabolism. Cardiovascular Research. 107(2), pp. 235 - 245. https://doi.org/10.1093/cvr/cvv166

Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis

O'Brien, Andrew J., Villani, Linda A., Broadfield, Lindsay A., Houde, Vanessa P., Galic, Sandra, Blandino, Giovanni, Kemp, Bruce Ernest, Tsakiridis, Theodoros, Muti, Paola and Steinberg, Gregory R.. (2015). Salicylate activates AMPK and synergizes with metformin to reduce the survival of prostate and lung cancer cells ex vivo through inhibition of de novo lipogenesis. Biochemical Journal. 469(2), pp. 177 - 187. https://doi.org/10.1042/Bj20150122

The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice

Marcinko, Katarina, Bujak, Adam L., Lally, James S. V., Ford, Rebecca J., Wong, Tammy H., Smith, Brennan K., Kemp, Bruce Ernest, Jenkins, Yonchu, Li, Wei, Kinsella, Todd M., Hitoshi, Yasumichi and Steinberg, Gregory R.. (2015). The AMPK activator R419 improves exercise capacity and skeletal muscle insulin sensitivity in obese mice. Molecular Metabolism. 4(9), pp. 643 - 651. https://doi.org/10.1016/j.molmet.2015.06.002

AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging

Bujak, Adam L., Crane, Justin D., Lally, James S., Ford, Rebecca J., Kang, Sally J., Rebalka, Irena A., Green, Alex E., Kemp, Bruce Ernest, Hawke, Thomas J., Schertzer, Jonathan D. and Steinberg, Gregory R.. (2015). AMPK activation of muscle autophagy prevents fasting-induced hypoglycemia and myopathy during aging. Cell Metabolism. 21(6), pp. 883 - 890. https://doi.org/10.1016/j.cmet.2015.05.016

Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging

Crane, Justin D., MacNeil, Lauren G., Lally, James S. V., Ford, Rebecca J., Bujak, Adam L., Brar, Ikdip K., Kemp, Bruce Ernest, Raha, Sandeep, Steinberg, Gregory Robert and Tarnopolsky, Mark A.. (2015). Exercise-stimulated interleukin-15 is controlled by AMPK and regulates skin metabolism and aging. Aging Cell. 14(4), pp. 625 - 634. https://doi.org/10.1111/acel.12341

Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder

Scott, John, Park, Elizabeth, Rodriguiz, Ramona, Oakhill, Jonathan, Issa, Samah, O'Brien, Matthew, Dite, Toby, Langendorf, Christopher, Wetsel, William, Means, Anthony and Kemp, Bruce. (2015). Autophosphorylation of CaMKK2 generates autonomous activity that is disrupted by a T85S mutation linked to anxiety and bipolar disorder. Scientific Reports. 5, pp. 1 - 10. https://doi.org/10.1038/srep14436

SnRK1 from Arabidopsis thaliana is an atypical AMPK

Emanuelle, Shane, Hossain, Mohammed Iqbal, Moller, Isabel E., Pedersen, Henriette L., van de Meene, Allison M. L., Doblin, Monika S., Koay, Ann, Oakhill, Jonathan S., Scott, John W., Willats, William G. T., Kemp, Bruce Ernest, Bacic, Antony, Gooley, Paul R. and Stapleton, David I.. (2015). SnRK1 from Arabidopsis thaliana is an atypical AMPK. Plant Journal. 82(2), pp. 183 - 192. https://doi.org/10.1111/tpj.12813

PPARδ Activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity

Bojic, Lazar, Telford, Dawn, Fullerton, Morgan, Ford, Rebecca, Sutherland, Brian, Edwards, Jane, Sawyez, Cynthia, Gros, Robert, Kemp, Bruce, Steinberg, Gregory and Huff, Murray. (2014). PPARδ Activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity. Journal of Lipid Research. 55(7), pp. 1254 - 1266. https://doi.org/10.1194/jlr.M046037

PPARδ activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity

Bojic, Lazar A., Telford, Dawn E., Fullerton, Morgan D., Ford, Rebecca J., Sutherland, Brian G., Edwards, Jane Y., Sawyez, Cynthia G., Gros, Robert, Kemp, Bruce Ernest, Steinberg, Gregory R. and Huff, Murray W.. (2014). PPARδ activation attenuates hepatic steatosis in Ldlr−/− mice by enhanced fat oxidation, reduced lipogenesis, and improved insulin sensitivity. Journal of Lipid Research. 55(7), pp. 1254 - 1266. https://doi.org/10.1194/jlr.M046037

Muscle-specific AMPK ß1ß2-null mice display a myopathy due to loss of capillary density in nonpostural muscles

Thomas, Melissa, Wang, David, D'Souza, Donna, Krause, Matthew, Layne, Andrew, Criswell, David, O'Neill, Hayley, Connor, Michael, Anderson, Judy, Kemp, Bruce, Steinberg, Gregory and Hawke, Thomas. (2014). Muscle-specific AMPK ß1ß2-null mice display a myopathy due to loss of capillary density in nonpostural muscles. The FASEB Journal. 28(5), pp. 2098 - 2107. https://doi.org/10.1096/fj.13-238972

Evidence for the role of AMPK in regulating PGC-1 alpha expression and mitochondrial proteins in mouse epididymal adipose tissue

Wan, Zhongxiao, Root-Mccaig, Jared, Castellani, Laura, Kemp, Bruce, Steinberg, Gregory and Wright, David. (2014). Evidence for the role of AMPK in regulating PGC-1 alpha expression and mitochondrial proteins in mouse epididymal adipose tissue. Obesity: a resourch journal. 22(3), pp. 730 - 738. https://doi.org/10.1002/oby.20605

Activation of AMPK reduces the co-transporter activity of NKCC1

Fraser, Scott A., Davies, Matthew R. P., Katerelos, Marina, Gleich, Kurt, Choy, Suet-Wan, Steel, Rohan, Galic, Sandra, Mount, Peter F., Kemp, Bruce Ernest and Power, David A.. (2014). Activation of AMPK reduces the co-transporter activity of NKCC1. Molecular Membrane Biology. 31(2-3), pp. 95 - 102. https://doi.org/10.3109/09687688.2014.902128

Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models

Perera, Nirma, Sheean, Rebecca, Scott, John, Kemp, Bruce, Horne, Malcolm and Turner, Bradley. (2014). Mutant TDP-43 deregulates AMPK activation by PP2A in ALS models. PLoS One (online). 9(3), pp. 1 - 11. https://doi.org/10.1371/journal.pone.0090449

Reduced skeletal muscle AMPK and mitochondrial markers do not promote age-induced insulin resistance

Bujak, Adam, Blumer, Regje, Marcinko, Katarina, Fullerton, Morgan, Kemp, Bruce and Steinberg, Gregory. (2014). Reduced skeletal muscle AMPK and mitochondrial markers do not promote age-induced insulin resistance. Journal of Applied Physiology. 117(2), pp. 171 - 179. https://doi.org/10.1152/japplphysiol.01101.2013

Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress

McGee, Sean, Swinton, Courtney, Morrison, Shona, Gaur, Vidhi, Campbell, Duncan, Jorgensen, Sebastian, Kemp, Bruce, Baar, Keith, Steinberg, Gregory and Hargreaves, Mark. (2014). Compensatory regulation of HDAC5 in muscle maintains metabolic adaptive responses and metabolism in response to energetic stress. The FASEB Journal. 28(8), pp. 3384 - 3395. https://doi.org/10.1096/fj.14-249359

ATP sensitive bi-quinoline activator of the AMP-activated protein kinase

Scott, John, Oakhill, Jonathan, Ling, Naomi, Langendorf, Christopher, Foitzik, Richard, Kemp, Bruce and Issinger, Olaf-Georg. (2014). ATP sensitive bi-quinoline activator of the AMP-activated protein kinase. Biochemical and Biophysical Research Communications. 443(2), pp. 435 - 440. https://doi.org/10.1016/j.bbrc.2013.11.130

Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662

Ducommun, Serge, Ford, Rebecca J., Bultot, Laurent, Deak, Maria, Bertrand, Luc, Kemp, Bruce Ernest, Steinberg, Gregory R. and Sakamoto, Kei. (2014). Enhanced activation of cellular AMPK by dual-small molecule treatment: AICAR and A769662. American Journal of Physiology - Endocrinology and Metabolism. 306(6), pp. 688 - 696. https://doi.org/10.1152/ajpendo.00672.2013

Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling

Scott, John, Ling, Naomi, Issa, Samah, Dite, Toby, O'Brien, Matthew, Chen, Zhi-Ping, Galic, Sandra, Langendorf, Christopher, Steinberg, Gregory, Kemp, Bruce and Oakhill, Jonathan. (2014). Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Chemistry and Biology. 21(5), pp. 619 - 627. https://doi.org/10.1016/j.chembiol.2014.03.006

Novel mechanisms of Na+ retention in obesity: Phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK

Davies, Matthew R. P., Fraser, Scott A., Galic, Sandra, Choy, Suet-Wan, Katerelos, Marina, Gleich, Kurt, Kemp, Bruce Ernest, Mount, Peter F. and Power, David A.. (2014). Novel mechanisms of Na+ retention in obesity: Phosphorylation of NKCC2 and regulation of SPAK/OSR1 by AMPK. American Journal of Physiology - Renal Physiology. 307(1), pp. 96 - 106. https://doi.org/10.1152/ajprenal.00524.2013

Mechanism of action of compound-13 : An a1-selective small molecule activator of AMPK

Hunter, Roger, Foretz, Marc, Bultot, Laurent, Fullerton, Morgan, Deak, Maria, Ross, Fiona, Hawley, Simon, Shpiro, Natalia, Viollet, Benoit, Barron, Denis, Kemp, Bruce, Steinberg, Gregory, Hardie, David Grahame and Sakamoto, Kei. (2014). Mechanism of action of compound-13 : An a1-selective small molecule activator of AMPK. Chemistry and Biology. 21(7), pp. 866 - 879. https://doi.org/10.1016/j.chembiol.2014.05.014

Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin

Fullerton, Morgan, Galic, Sandra, Marcinko, Katarina, Sikkema, Sarah, Pulinilkunnil, Thomas, Chen, Zhi-Ping, O'Neill, Hayley, Ford, Rebecca, Palanivel, Rengasamy, O'Brien, Matthew, Hardie, D. Grahame, Macaulay, Lance, Schertzer, Jonathan, Dyck, Jason, van Denderen, Bryce, Kemp, Bruce and Steinberg, Gregory. (2013). Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nature Medicine. 19(12), pp. 1649 - 1654. https://doi.org/10.1038/nm.3372

AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice

O’Neill, Hayley M., Lally, James S., Galic, Sandra, Thomas, Melissa, Azizi, Paymon D., Fullerton, Morgan D., Smith, Brennan K., Pulinilkunnil, Thomas, Chen, Zhiping, Constantine Samaan, M., Jorgensen, Sebastian B., Dyck, Jason R. B., Holloway, Graham P., Hawke, Thomas J., van Denderen, Bryce J., Kemp, Bruce E. and Steinberg, Gregory R.. (2012). AMPK phosphorylation of ACC2 is required for skeletal muscle fatty acid oxidation and insulin sensitivity in mice. Diabetologia. 57(8), pp. 1693 - 1702. https://doi.org/10.1007/s00125-014-3273-1

AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation

Zordoky, Beshay N.M., Nagendran, Jeevan, Pulinilkunnil, Thomas, Kienesberger, Petra C., Masson, Grant, Waller, Terri J., Kemp, Bruce E., Steinberg, Gregory R. and Dyck, Jason R. B.. (2012). AMPK-dependent inhibitory phosphorylation of ACC is not essential for maintaining myocardial fatty acid oxidation. Circulation Research. 115(5), pp. 518 - 524. https://doi.org/10.1161/CIRCRESAHA.115.304538

The ancient drug salicylate directly activates AMP-activated protein kinase

Hawley, Simon, Fullerton, Morgan, Ross, Fiona, Schertzer, Jonathan, Chevtzoff, Cyrille, Walker, Katherine, Peggie, Mark, Zibrova, Darya, Green, Kevin, Mustard, Kirsty, Kemp, Bruce, Sakamoto, Kei, Steinberg, Gregory and Hardie, D. Grahame. (2012). The ancient drug salicylate directly activates AMP-activated protein kinase. Science. 336(6083), pp. 918 - 922. https://doi.org/10.1126/science.1215327

Pro-GRP-derived peptides are expressed in colorectal cancer cells and tumors and are biologically active in vivo

Patel, Oneel, Clyde, Daniel, Chang, Mike, Nordlund, Marianne, Steel, Rohan, Kemp, Bruce, Pritchard, D. Mark, Shulkes, Arthur and Baldwin, Graham. (2012). Pro-GRP-derived peptides are expressed in colorectal cancer cells and tumors and are biologically active in vivo. Endocrinology. 153(3), pp. 1082 - 1092. https://doi.org/10.1210/en.2011-1875

The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-ß1 deficient mice

Mount, Peter, Gleich, Kurt, Tam, Shanna, Fraser, Scott, Choy, Suet-Wan, Dwyer, Karen, Lu, Bo, Van Denderen, Bryce, Fingerle-Rowson, Gunter, Bucala, Richard, Kemp, Bruce and Power, David. (2012). The outcome of renal ischemia-reperfusion injury is unchanged in AMPK-ß1 deficient mice. PLoS One (online). 7(1), pp. 1 - 10. https://doi.org/10.1371/journal.pone.0029887

Inhibition of the heterotetrameric K+ channel KCNQ1/KCNE1 by the AMP-activated protein kinase

Alesultan, Ioana, Foller, Michael, Sopjani, Mentor, Dermaku-Sopjani, Miribane, Zelenak, Christine, Frohlich, Henning, Velic, Ana, Fraser, Scott, Kemp, Bruce, Seebohm, Guiscard, Volkl, Harald and Lang, Florian. (2011). Inhibition of the heterotetrameric K+ channel KCNQ1/KCNE1 by the AMP-activated protein kinase. Molecular Membrane Biology. 28(2), pp. 79 - 89. https://doi.org/10.3109/09687688.2010.520037

AMP-activated protein kinase (AMPK) ß1ß2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise

O'Neill, Hayley M., Maarbjerg, Stine J., Crane, Justin D., Jeppesen, Jacob, Jorgensen, Sebastian B., Schertzer, Jonathan D., Shyroka, Olga, Kiens, Bente, Van Denderen, Bryce J., Tarnopolsky, Mark A., Kemp, Bruce Ernest, Richter, Erik A. and Steinberg, Gregory R.. (2011). AMP-activated protein kinase (AMPK) ß1ß2 muscle null mice reveal an essential role for AMPK in maintaining mitochondrial content and glucose uptake during exercise. Proceedings of the National Academy of Sciences of USA. 108(38), pp. 16092 - 16097. https://doi.org/10.1073/pnas.1105062108

Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation

Green, Michelle, Scott, John, Steel, Rohan, Oakhill, Jonathan, Kemp, Bruce and Means, Anthony. (2011). Ca 2+/calmodulin-dependent protein kinase kinase beta is regulated by multisite phosphorylation. Journal of Biological Chemistry. 286(32), pp. 28066 - 28079. https://doi.org/10.1074/jbc.M111.251504

Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity

Galic, Sandra, Fullerton, Morgan, Schertzer, Jonathan, Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl, Izon, David, Honeyman, Jane, Chen, Zhi-Ping, Van Denderen, Bryce, Kemp, Bruce and Steinberg, Gregory. (2011). Hematopoietic AMPK beta1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577

Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity

Galic, Sandra, Fullerton, Morgan D., Schertzer, Jonathan D., Sikkema, Sarah, Marcinko, Katarina, Walkley, Carl R., Izon, David, Honeyman, Jane, Chen, Zhi-Ping, van Denderen, Bryce J., Kemp, Bruce Ernest and Steinberg, Gregory R.. (2011). Hematopoietic AMPK Beta ß1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity. Journal of Clinical Investigation. 121(12), pp. 4903 - 4915. https://doi.org/10.1172/JCI58577

Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase

Alesutan, Ioana, Munoz, Carlos, Sopjani, Mentor, Dermaku-Sopjani, Miribane, Michael, Diana, Fraser, Scott, Kemp, Bruce, Seebohm, Guiscard, Foller, Michael and Lang, Florian. (2011). Inhibition of Kir2.1 (KCNJ2) by the AMP-activated protein kinase. Biochemical and Biophysical Research Communications. 408(4), pp. 505 - 510. https://doi.org/10.1016/j.bbrc.2011.04.015

Inhibition of Connexin 26 by the AMP-activated protein kinase

Alesutan, Ioana, Sopjani, Mentor, Munoz, Carlos, Fraser, Scott, Kemp, Bruce, Foller, Michael and Lang, Florian. (2011). Inhibition of Connexin 26 by the AMP-activated protein kinase. Journal of Membrane Biology: an international journal for studies on the structure, function and genesis of biomembranes. 240(3), pp. 151 - 158. https://doi.org/10.1007/s00232-011-9353-y

AMPK is a direct adenylate charge-regulated protein kinase

Oakhill, Jonathan S., Steel, Rohan, Chen, Zhi-Ping, Scott, John W., Ling, Naomi, Tam, Shanna and Kemp, Bruce Ernest. (2011). AMPK is a direct adenylate charge-regulated protein kinase. Science. 332(6036), pp. 1433 - 1435. https://doi.org/10.1126/science.1200094

AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1

Fraser, Scott A., Choy, Suet-Wan, Pastor-Soler, Núria M., Li, Hui, Davies, Matthew R. P., Cook, Natasha, Katerelos, Marina, Mount, Peter F., Gleich, Kurt, McRae, Jennifer L., Dwyer, Karen M., van Denderen, Bryce J. W., Hallows, Kenneth R., Kemp, Bruce E. and Power, David A.. (2010). AMPK couples plasma renin to cellular metabolism by phosphorylation of ACC1. American Journal of Physiology - Renal Physiology. 305(5), pp. F679 - F690. https://doi.org/10.1152/ajprenal.00407.2012

Impaired skeletal muscle beta-adrenergic activation and lipolysis are associated with whole-body insulin resistance in rats bred for low intrinsic exercise capacity

Lessard, Sarah J., Rivas, Donato A., Chen, Zhu-Ping, van Denderen, Bryce J., Watt, Matthew J., Koch, Lauren G., Britton, Steven L., Kemp, Bruce Ernest and Hawley, John Alan. (2009). Impaired skeletal muscle beta-adrenergic activation and lipolysis are associated with whole-body insulin resistance in rats bred for low intrinsic exercise capacity. Endocrinology. 150(11), pp. 4883 - 4891. https://doi.org/10.1210/en.2009-0158

Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans

Yeo, Wee Kian, Lessard, Sarah J., Chen, Zhi-Ping, Garnham, Andrew P., Burke, Louise, Rivas, Donato A., Kemp, Bruce Ernest and Hawley, John Alan. (2008). Fat adaptation followed by carbohydrate restoration increases AMPK activity in skeletal muscle from trained humans. Journal of Applied Physiology. 105(5), pp. 1519 - 1526. https://doi.org/10.1152/japplphysiol.90540.2008

Activation of AMPK reduces the co-transporter activity of NKCC1

Fraser, Scott A., Davies, Matthew, Katerelos, Marina, Gleich, Kurt, Choy, Suet-Wan, Steel, Rohan, Galic, Sandra, Mount, Peter F., Kemp, Bruce E. and Power, David A.. (1999). Activation of AMPK reduces the co-transporter activity of NKCC1. Molecular Membrane Biology. 31(2-3), pp. 95 - 102. https://doi.org/10.3109/09687688.2014.902128

Myosin light chain kinases

Kemp, Bruce E. and Stull, James T.. (1990). Myosin light chain kinases. In In B. E. Kemp (Ed.). Peptides and Protein Phosphorylation pp. 115 - 133 CRC Press. https://doi.org/10.1201/9781351075442