AccScience Publishing / ITPS / Online First / DOI: 10.36922/itps.4852
Submit to ITPS
Cite this article
4
Download
110
Views
Journal Browser
Volume | Year
Issue
Search
Forthcoming Issue
Current Issue
View All
News and Announcements
View All
REVIEW ARTICLE

The role of AMPK activation in metabolic regulation, energy homeostasis and aging: A comprehensive overview

George Jîtcă*
Show Less
1 Department of Pharmacology and Clinical Pharmacy, Faculty of Pharmacy, George Emil Palade University of Medicine, Pharmacy, Science and Technology of Târgu Mureş, 540139 Târgu Mureş, Romania
INNOSC Theranostics and Pharmacological Sciences, 4852 https://doi.org/10.36922/itps.4852
Submitted: 14 September 2024 | Revised: 13 December 2024 | Accepted: 16 December 2024 | Published: 31 December 2024
© 2024 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
Download PDF
Cite
XML
Abstract

5’ Adenosine monophosphate-activated protein kinase (AMPK) is a metabolic sensor responsible for maintaining homeostasis, regulating metabolic control, monitoring energy status, and balancing energy production with consumption. The most important protein kinases that activate AMPK are liver kinase B1 and calcium-calmodulin-dependent protein kinase. AMPK significantly impacts physical performance by accelerating recovery periods and restoring energy stores through several key mechanisms. It regulates muscle glycogen content, ensuring readily available energy during physical exertion. In addition, a high number of mitochondria enable the utilization of fatty acids as an energy source, thereby improving endurance efforts. Furthermore, rich vascularization in the muscles enhances the delivery of nutrients and oxygen, optimizing performance and speeding up recovery. AMPK is also important for maintaining muscle homeostasis. It decreases insulin resistance, stimulates mitochondrial biogenesis, and exerts an antioxidant effect. As a regulator of energy homeostasis, AMPK plays a key role in linking cellular energy levels with the aging process. It acts as a modulator of cellular senescence and has the potential to extend life expectancy, particularly in the context of caloric restriction. By activating AMPK, caloric restriction (activated with a 30 – 70% reduction in nutrient intake) helps to maintain energy balance in cells, which may slow down aging and support healthier cellular function over time. In conclusion, the involvement of AMPK in metabolic regulation and maintenance makes it an important therapeutic target for the treatment and prevention of several diseases, both age-related and otherwise.

Keywords
AMPK
Oxidative stress
Physical effort
Exercise
Metabolism
Funding
None.
Conflict of interest
The author declares has no competing interests.
References
  1. Carling D, Zammit VA, Hardie DG. A common bicyclic protein kinase cascade inactivates the regulatory enzymes of fatty acid and cholesterol biosynthesis. FEBS Lett. 1987;223:217-222. doi: 10.1016/0014-5793(87)80292-2

 

  1. Niederberger E, King TS, Russe OQ, Geisslinger G. Activation of AMPK and its impact on exercise capacity. Sports Med. 2015;45:1497-1509. doi: 10.1007/s40279-015-0366-z

 

  1. López M. Hypothalamic AMPK and energy balance. Eur J Clin Invest. 2018;48:e12996. doi: 10.1111/eci.12996

 

  1. Richter EA, Ruderman NB. AMPK and the biochemistry of exercise: Implications for human health and disease. Biochem J. 2009;418:261-275. doi: 10.1042/BJ20082055

 

  1. Kim J, Yang G, Kim Y, Kim J, Ha J. AMPK activators: Mechanisms of action and physiological activities. Exp Mol Med. 2016;48:e224. doi: 10.1038/emm.2016.16

 

  1. Hardie DG, Ross FA, Hawley SA. AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat Rev Mol Cell Biol. 2012;13:251-262. doi: 10.1038/nrm3311

 

  1. Ren Y, Shen HM. Critical role of AMPK in redox regulation under glucose starvation. Redox Biol. 2019;25:101154. doi: 10.1016/j.redox.2019.101154

 

  1. Willows R, Navaratnam N, Lima A, Read J, Carling D. Effect of different γ-subunit isoforms on the regulation of AMPK. Biochem J. 2017;474:1741-1754. doi: 10.1042/BCJ20170046

 

  1. Ross FA, Jensen TE, Hardie DG. Differential regulation by AMP and ADP of AMPK complexes containing different γ subunit isoforms. Biochem J. 2016;473:189-199. doi: 10.1042/BJ20150910

 

  1. Zhang CS, Lin SC. AMPK promotes autophagy by facilitating mitochondrial fission. Cell Metab. 2016;23:399-401. doi: 10.1016/j.cmet.2016.02.017

 

  1. Lin SC, Hardie DG. AMPK: Sensing glucose as well as cellular energy status. Cell Metab. 2018;27:299-313. doi: 10.1016/j.cmet.2017.10.009

 

  1. Ježek J, Cooper KF, Strich R. Reactive oxygen species and mitochondrial dynamics: The Yin and Yang of mitochondrial dysfunction and cancer progression. Antioxidants (Basel). 2018;7:13. doi: 10.3390/antiox7010013

 

  1. Jîtcă G, Ősz BE, Tero-Vescan A, et al. Positive aspects of oxidative stress at different levels of the human body: A review. Antioxidants (Basel). 2022;11:572. doi: 10.3390/antiox11030572

 

  1. Liu H, Xu Y, Hu F. AMPK in the ventromedial nucleus of the hypothalamus: A key regulator for thermogenesis. Front Endocrinol (Lausanne). 2020;11:578830. doi: 10.3389/fendo.2020.578830

 

  1. Josep A. Villena New insights into PGC-1 coactivators: Redefining their role in the regulation of mitochondrial function and beyond. FEBS J. 2015;282:647-672. doi: 10.1111/febs.13175

 

  1. Li L, Pan R, Li R, et al. Mitochondrial biogenesis and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) deacetylation by physical activity: Intact adipocytokine signaling is required. Diabetes. 2011;60:157-167. doi: 10.2337/db10-0331

 

  1. Zhou G, Myers R, Li Y, et al. Role of AMP-activated protein kinase in mechanism of metformin action. J Clin Invest. 2001;108:1167-1174. doi: 10.1172/JCI13505

 

  1. Hawley SA, Ford RJ, Smith BK, et al. The Na+/glucose cotransporter inhibitor canagliflozin activates AMPK by inhibiting mitochondrial function and increasing cellular AMP levels. Diabetes. 2016;65:2784-2794. doi: 10.2337/db16-0058

 

  1. O’Brien AJ, Villani LA, Broadfield LA, et al. 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. Biochem J. 2015;469:177-187. doi: 10.1042/BJ20150122

 

  1. Yun H, Ha J. AMP-activated protein kinase modulators: A patent review (2006-2010). Expert Opin Ther Pat. 2011;21:983-1005. doi: 10.1517/13543776.2011.577069

 

  1. Madiraju AK, Erion DM, Rahimi Y, et al. Metformin suppresses gluconeogenesis by inhibiting mitochondrial glycerophosphate dehydrogenase. Nature. 2014;510:542-546. doi: 10.1038/nature13270

 

  1. Ruderman NB, Keller C, Richard AM, et al. Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes. 2006;55:S48-S54. doi: 10.2337/db06-s007

 

  1. Grahame Hardie D. Regulation of AMP-activated protein kinase by natural and synthetic activators. Acta Pharm Sin B. 2016;6:1-19. doi: 10.1016/j.apsb.2015.06.002

 

  1. Lee JM, Seo WY, Song KH, et al. AMPK-dependent repression of hepatic gluconeogenesis via disruption of CREB.CRTC2 complex by orphan nuclear receptor small heterodimer partner. J Biol Chem. 2010;285:32182-32191. doi: 10.1074/jbc.M110.134890

 

  1. Guttzeit S, Backs J. Post-translational modifications talk and crosstalk to class IIa histone deacetylases. J Mol Cell Cardiol. 2022;162:53-61. doi: 10.1016/j.yjmcc.2021.08.007

 

  1. Zhang BB, Zhou G, Li C. AMPK: An emerging drug target for diabetes and the metabolic syndrome. Cell Metab. 2009;9:407-416. doi: 10.1016/j.cmet.2009.03.012

 

  1. Foretz M, Even PC, Viollet B. AMPK activation reduces hepatic lipid content by increasing fat oxidation in vivo. Int J Mol Sci. 2018;19:2826. doi: 10.3390/ijms19092826

 

  1. Herzig S, Shaw RJ. AMPK: Guardian of metabolism and mitochondrial homeostasis. Nat Rev Mol Cell Biol. 2018;19:121-135. doi: 10.1038/nrm.2017.95

 

  1. Rehman G, Shehzad A, Khan AL, Hamayun M. Role of AMP-activated protein kinase in cancer therapy. Arch Pharm (Weinheim). 2014;347:457-468. doi: 10.1002/ardp.201300402

 

  1. Alessi DR, Sakamoto K, Bayascas JR. LKB1-dependent signaling pathways. Annu Rev Biochem. 2006;75:137-163. doi: 10.1146/annurev.biochem.75.103004.142702

 

  1. Egan DF, Shackelford DB, Mihaylova MM, et al. Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy. Science. 2011;331:456-461. doi: 10.1126/science.1196371

 

  1. Kim J, Kim YC, Fang C, et al. Differential regulation of distinct Vps34 complexes by AMPK in nutrient stress and autophagy. Cell. 2013;152:290-303. doi: 10.1016/j.cell.2012.12.016

 

  1. Jansen T, Kvandová M, Daiber A, et al. The AMP-activated protein kinase plays a role in antioxidant defense and regulation of vascular inflammation. Antioxidants (Basel). 2020;9:525. doi: 10.3390/antiox9060525

 

  1. Mounier R, Théret M, Lantier L, Foretz M, Viollet B. Expanding roles for AMPK in skeletal muscle plasticity. Trends Endocrinol Metab. 2015;26:275-286. doi: 10.1016/j.tem.2015.02.009

 

  1. Hall DT, Griss T, Ma JF, et al. The AMPK agonist 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), but not metformin, prevents inflammation-associated cachectic muscle wasting. EMBO Mol Med. 2018;10:e8307. doi: 10.15252/emmm.201708307

 

  1. Sartori R, Romanello V, Sandri M. Mechanisms of muscle atrophy and hypertrophy: Implications in health and disease. Nat Commun. 2021;12:330. doi: 10.1038/s41467-020-20123-1

 

  1. Shang R, Miao J. Mechanisms and effects of metformin on skeletal muscle disorders. Front Neurol. 2023;14:1275266. doi: 10.3389/fneur.2023.1275266

 

  1. Neufer PD, Bamman MM, Muoio DM, et al. Understanding the cellular and molecular mechanisms of physical activity-induced health benefits. Cell Metab. 2015;22:4-11. doi: 10.1016/j.cmet.2015.05.011

 

  1. Fan W, Evans RM. Exercise mimetics: Impact on health and performance. Cell Metab. 2017;25:242-247. doi: 10.1016/j.cmet.2016.10.022

 

  1. Guerrieri D, Moon HY, van Praag H. Exercise in a pill: The latest on exercise-mimetics. Brain Plast. 2017;2:153-169. doi: 10.3233/BPL-160043

 

  1. Gubert C, Hannan AJ. Exercise mimetics: Harnessing the therapeutic effects of physical activity. Nat Rev Drug Discov. 2021;20:862-879. doi: 10.1038/s41573-021-00217-1

 

  1. Ouchi N, Shibata R, Walsh K. AMP-activated protein kinase signaling stimulates VEGF expression and angiogenesis in skeletal muscle. Circ Res. 2005;96:838-846. doi: 10.1161/01.RES.0000163633.10240.3b

 

  1. Treins C, Murdaca J, Van Obberghen E, Giorgetti-Peraldi S. AMPK activation inhibits the expression of HIF-1alpha induced by insulin and IGF-1. Biochem Biophys Res Commun. 2006;342:1197-1202. doi: 10.1016/j.bbrc.2006.02.088

 

  1. Kobilo T, Guerrieri D, Zhang Y, Collica SC, Becker KG, van Praag H. AMPK agonist AICAR improves cognition and motor coordination in young and aged mice. Learn Mem. 2014;21:119-126. doi: 10.1101/lm.033332.113

 

  1. Guerrieri D, van Praag H. Exercise-mimetic AICAR transiently benefits brain function. Oncotarget. 2015;6:18293-18313. doi: 10.18632/oncotarget.4715

 

  1. Hawley SA, Ross FA, Chevtzoff C, et al. Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation. Cell Metab. 2010;11:554-565. doi: 10.1016/j.cmet.2010.04.001

 

  1. Jeon SM. Regulation and function of AMPK in physiology and diseases. Exp Mol Med. 2016;48:e245. doi: 10.1038/emm.2016.81

 

  1. Marino A, Hausenloy DJ, Andreadou I, Horman S, Bertrand L, Beauloye C. AMP-activated protein kinase: A remarkable contributor to preserve a healthy heart against ROS injury. Free Radic Biol Med. 2021;166:238-254. doi: 10.1016/j.freeradbiomed.2021.02.047

 

  1. Foretz M, Guigas B, Viollet B. Metformin: Update on mechanisms of action and repurposing potential. Nat Rev Endocrinol. 2023;19:460-476. doi: 10.1038/s41574-023-00833-4

 

  1. Möller I, Wintermeyer A, Bender K, et al. Screening for the synthetic cannabinoid JWH-018 and its major metabolites in human doping controls. Drug Test Anal. 2011;3:609-620. doi: 10.1002/dta.158

 

  1. Regensteiner JG, Bauer TA, Reusch JE. Rosiglitazone improves exercise capacity in individuals with type 2 diabetes. Diabetes Care. 2005;28:2877-2883. doi: 10.2337/diacare.28.12.2877

 

  1. Roi GS, Garagiola U, Verza P, et al. Aspirin does not affect exercise performance. Int J Sports Med. 1994;15:224-227. doi: 10.1055/s-2007-1021050

 

  1. Rencurel F, Stenhouse A, Hawley SA, et al. AMP-activated protein kinase mediates phenobarbital induction of CYP2B gene expression in hepatocytes and a newly derived human hepatoma cell line. J Biol Chem. 2005;280:4367-4373. doi: 10.1074/jbc.M412711200

 

  1. Feng X, Luo Z, Ma L, et al. Angiotensin II receptor blocker telmisartan enhances running endurance of skeletal muscle through activation of the PPAR-δ/AMPK pathway. J Cell Mol Med. 2011;15:1572-1581. doi: 10.1111/j.1582-4934.2010.01085.x

 

  1. Hart N, Sarga L, Csende Z, et al. Resveratrol attenuates exercise-induced adaptive responses in rats selectively bred for low running performance. Dose Response. 2013;12:57-71. doi: 10.2203/dose-response.13-010.Radak

 

  1. Mnatsakanyan N, Jonas EA. The new role of F1Fo ATP synthase in mitochondria-mediated neurodegeneration and neuroprotection. Exp Neurol. 2020;332:113400. doi: 10.1016/j.expneurol.2020.113400

 

  1. Althaher AR, Alwahsh M. An overview of ATP synthase, inhibitors, and their toxicity. Heliyon. 2023;9:e22459. doi: 10.1016/j.heliyon.2023.e22459

 

  1. Zheng J, Ramirez VD. Inhibition of mitochondrial proton F0F1-ATPase/ATP synthase by polyphenolic phytochemicals. Br J Pharmacol. 2000;130:1115-1123. doi: 10.1038/sj.bjp.0703397

 

  1. Fang X, Wu H, Wei J, Miao R, Zhang Y, Tian J. Research progress on the pharmacological effects of berberine targeting mitochondria. Front Endocrinol (Lausanne). 2022;13:982145. doi: 10.3389/fendo.2022.982145

 

  1. Liu Z, Cui C, Xu P, et al. Curcumin activates AMPK pathway and regulates lipid metabolism in rats following prolonged clozapine exposure. Front Neurosci. 2017;11:558. doi: 10.3389/fnins.2017.00558

 

  1. Zhang X, Wang L, Guo R, et al. Ginsenoside Rb1 ameliorates diabetic arterial stiffening via AMPK pathway. Front Pharmacol. 2021;12:753881. doi: 10.3389/fphar.2021.753881

 

  1. Wang Y, Li X, Guo Y, Chan L, Guan X. alpha-Lipoic acid increases energy expenditure by enhancing adenosine monophosphate-activated protein kinase-peroxisome proliferator-activated receptor-gamma coactivator-1alpha signaling in the skeletal muscle of aged mice. Metabolism. 2010;59:967-976. doi: 10.1016/j.metabol.2009.10.018

 

  1. Dean S, Braakhuis A, Paton C. The effects of EGCG on fat oxidation and endurance performance in male cyclists. Int J Sport Nutr Exerc Metab. 2009;19:624-644. doi: 10.1123/ijsnem.19.6.624

 

  1. Chen W, Pan Y, Wang S, et al. Cryptotanshinone activates AMPK-TSC2 axis leading to inhibition of mTORC1 signaling in cancer cells. BMC Cancer. 2017;17:34. doi: 10.1186/s12885-016-3038-y

 

  1. Luo Z, Ma L, Zhao Z, et al. TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice. Cell Res. 2012;22:551-564. doi: 10.1038/cr.2011.205

 

  1. Wu RM, Sun YY, Zhou TT, et al. Arctigenin enhances swimming endurance of sedentary rats partially by regulation of antioxidant pathways. Acta Pharmacol Sin. 2014;35:1274-1284. doi: 10.1038/aps.2014.70

 

  1. Jeong HW, Cho SY, Kim S, et al. Chitooligosaccharide induces mitochondrial biogenesis and increases exercise endurance through the activation of Sirt1 and AMPK in rats. PLoS One. 2012;7(7):e40073. doi: 10.1371/journal.pone.0040073

 

  1. Murase T, Misawa K, Haramizu S, Minegishi Y, Hase T. Nootkatone, a characteristic constituent of grapefruit, stimulates energy metabolism and prevents diet-induced obesity by activating AMPK. Am J Physiol Endocrinol Metab. 2010;299:E266-E275. doi: 10.1152/ajpendo.00774.2009

 

  1. Baltgalvis KA, White K, Li W, et al. Exercise performance and peripheral vascular insufficiency improve with AMPK activation in high-fat diet-fed mice. Am J Physiol Heart Circ Physiol. 2014;306:H1128-H1145. doi: 10.1152/ajpheart.00839.2013

 

  1. Xu YY, Chen FL, Ji F, Fei HD, Xie Y, Wang SG. Activation of AMP-activated protein kinase by compound 991 protects osteoblasts from dexamethasone. Biochem Biophys Res Commun. 2018;495:1014-1021. doi: 10.1016/j.bbrc.2017.11.132

 

  1. Mo Y, Zhu JL, Jiang A, Zhao J, Ye L, Han B. Compound 13 activates AMPK-Nrf2 signaling to protect neuronal cells from oxygen glucose deprivation-reoxygenation. Aging (Albany NY). 2019;11:12032-12042. doi: 10.18632/aging.102534

 

  1. Jensen TE, Ross FA, Kleinert M, et al. PT-1 selectively activates AMPK-γ1 complexes in mouse skeletal muscle, but activates all three γ subunit complexes in cultured human cells by inhibiting the respiratory chain. Biochem J. 2015;467:461-472. doi: 10.1042/BJ20141142

 

  1. Zadra G, Photopoulos C, Tyekucheva S, et al. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med. 2014;6:519-538. doi: 10.1002/emmm.201302734

 

  1. Kudryavtseva AV, Krasnov GS, Dmitriev AA, et al. Mitochondrial dysfunction and oxidative stress in aging and cancer. Oncotarget. 2016;7:44879-44905. doi: 10.18632/oncotarget.9821

 

  1. Vatner SF, Zhang J, Oydanich M, Berkman T, Naftalovich R, Vatner DE. Healthful aging mediated by inhibition of oxidative stress. Ageing Res Rev. 2020;64:101194. doi: 10.1016/j.arr.2020.101194

 

  1. Hajam YA, Rani R, Ganie SY, et al. Oxidative stress in human pathology and aging: Molecular mechanisms and perspectives. Cells. 2022;11:552. doi: 10.3390/cells11030552

 

  1. Covarrubias AJ, Kale A, Perrone R, et al. Senescent cells promote tissue NAD+ decline during ageing via the activation of CD38+macrophages. Nat Metab. 2020;2:1265-1283. doi: 10.1038/s42255-020-00305-3

 

  1. de Lange P, Lombardi A, Silvestri E, et al. Physiological approaches targeting cellular and mitochondrial pathways underlying adipose organ senescence. Int J Mol Sci. 2023;24:11676. doi: 10.3390/ijms241411676

 

  1. Cavaliere G, Catapano A, Trinchese G, et al. Crosstalk between adipose tissue and hepatic mitochondria in the development of the inflammation and liver injury during ageing in high-fat diet fed rats. Int J Mol Sci. 2023;24:2967. doi: 10.3390/ijms24032967

 

  1. Weir HJ, Yao P, Huynh FK, et al. Dietary restriction and AMPK increase lifespan via mitochondrial network and peroxisome remodeling. Cell Metab. 2017;26:884-896.e5. doi: 10.1016/j.cmet.2017.09.024

 

  1. Bonda DJ, Lee HG, Camins A, et al. The sirtuin pathway in ageing and Alzheimer disease: Mechanistic and therapeutic considerations. Lancet Neurol. 2011;10:275-579. doi: 10.1016/S1474-4422(11)70013-8

 

  1. Leduc-Gaudet JP, Picard M, St-Jean Pelletier F, et al. Mitochondrial morphology is altered in atrophied skeletal muscle of aged mice. Oncotarget. 2015;6:17923-17937. doi: 10.18632/oncotarget.4235

 

  1. Leduc-Gaudet JP, Hussain SNA, Barreiro E, Gouspillou G. Mitochondrial dynamics and mitophagy in skeletal muscle health and aging. Int J Mol Sci. 2021;22:8179. doi: 10.3390/ijms22158179

 

  1. Patil SP, Jain PD, Ghumatkar PJ, Tambe R, Sathaye S. Neuroprotective effect of metformin in MPTP-induced Parkinson’s disease in mice. Neuroscience. 2014;277:747-754. doi: 10.1016/j.neuroscience.2014.07.046

 

  1. Shaw RJ, Lamia KA, Vasquez D, et al. The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science. 2005;310:1642-1646. doi: 10.1126/science.1120781

 

  1. Porter KM, Ward M, Hughes CF, et al. Hyperglycemia and metformin use are associated with B vitamin deficiency and cognitive dysfunction in older adults. J Clin Endocrinol Metab. 2019;104:4837-4847. doi: 10.1210/jc.2018-01791

 

  1. Sayedali E, Yalin AE, Yalin S. Association between metformin and vitamin B12 deficiency in patients with type 2 diabetes. World J Diabetes. 2023;14:585-593. doi: 10.4239/wjd.v14.i5.585

 

  1. Jiang HC, Hsu JM, Yen CP, Chao CC, Chen RH, Pan CL. Neural activity and CaMKII protect mitochondria from fragmentation in aging Caenorhabditis elegans neurons. Proc Natl Acad Sci U S A. 2015;112:8768-8773. doi: 10.1073/pnas.1501831112

 

  1. Sebastián D, Acín-Pérez R, Morino K. Mitochondrial health in aging and age-related metabolic disease. Oxid Med Cell Longev. 2016;2:5831538. doi: 10.1155/2016/5831538

 

  1. Aubert G, Mansuy V, Voirol MJ, Pellerin L, Pralong FP. The anorexigenic effects of metformin involve increases in hypothalamic leptin receptor expression. Metabolism. 2011;60:327-334. doi: 10.1016/j.metabol.2010.02.007

 

  1. Lin H, Ao H, Guo G, Liu M. The role and mechanism of metformin in inflammatory diseases. J Inflamm Res. 2023;16:5545-5564. doi: 10.2147/JIR.S436147

 

  1. Li X, Cai Y, Luo J, et al. Metformin attenuates hypothalamic inflammation via downregulation of RIPK1-independent microglial necroptosis in diet-induced obese mice. Cell Death Discov. 2021;7:338. doi: 10.1038/s41420-021-00732-5

 

  1. Bai B, Chen H. Metformin: A novel weapon against inflammation. Front Pharmacol. 2021;12:622262. doi: 10.3389/fphar.2021.622262

 

  1. Lutz W, Sanderson W, Scherbov S. The coming acceleration of global population ageing. Nature. 2008;451:716-719. doi: 10.1038/nature06516

 

  1. Alfaras I, Di Germanio C, Bernier M, et al. Pharmacological strategies to retard cardiovascular aging. Circ Res. 2016;118:1626-1642. doi: 10.1161/CIRCRESAHA.116.307475

 

  1. Nakamura S, Yoshimori T. Autophagy and longevity. Mol Cells. 2018;41:65-72. doi: 10.14348/molcells.2018.2333

 

  1. Ren J, Yang L, Zhu L, et al. Akt2 ablation prolongs life span and improves myocardial contractile function with adaptive cardiac remodeling: Role of Sirt1-mediated autophagy regulation. Aging Cell. 2017;16:976-987. doi: 10.1111/acel.12616

 

  1. Madeo F, Tavernarakis N, Kroemer G. Can autophagy promote longevity? Nat Cell Biol. 2010;12:842-846. doi: 10.1038/ncb0910-842

 

  1. Harrison D, Strong R, Sharp Z. Rapamycin fed late in life extends lifespan in genetically heterogeneous mice. Nature. 2009;460:392-395. doi: 10.1038/nature08221

 

  1. Kennedy BK, Lamming DW. The mechanistic target of rapamycin: The grand ConducTOR of metabolism and aging. Cell Metab. 2016;23:990-1003. doi: 10.1016/j.cmet.2016.05.009

 

  1. Zhang D, Contu R, Latronico MV, et al. MTORC1 regulates cardiac function and myocyte survival through 4E-BP1 inhibition in mice. J Clin Invest. 2010;120:2805-2816. doi: 10.1172/JCI43008

 

  1. Ulgherait M, Rana A, Rera M, Graniel J, Walker DW. AMPK modulates tissue and organismal aging in a non-cell-autonomous manner. Cell Rep. 2014;8:1767-1780. doi: 10.1016/j.celrep.2014.08.006

 

  1. Aman Y, Schmauck-Medina T, Hansen M, et al. Autophagy in healthy aging and disease. Nat Aging. 2021;1:634-650. doi: 10.1038/s43587-021-00098-4

 

  1. Locatelli AG, Cenci S. Autophagy and longevity: Evolutionary hints from hyper-longevous mammals. Front Endocrinol (Lausanne). 2022;13:1085522. doi: 10.3389/fendo.2022.1085522

 

  1. Shah AK, Gupta A, Dey CS. AICAR induced AMPK activation potentiates neuronal insulin signaling and glucose uptake. Arch Biochem Biophys. 2011;509:142-146. doi: 10.1016/j.abb.2011.03.005

 

  1. Ronnett GV, Ramamurthy S, Kleman AM, Landree LE, Aja S. AMPK in the brain: Its roles in energy balance and neuroprotection. J Neurochem. 2009;109:17-23. doi: 10.1111/j.1471-4159.2009.05916.x

 

  1. Oh TS, Cho H, Cho JH, Yu SW, Kim EK. Hypothalamic AMPK-induced autophagy increases food intake by regulating NPY and POMC expression. Autophagy. 2016;12:2009-2025. doi: 10.1080/15548627.2016.1215382

 

  1. Lim CT, Kola B, Korbonits M. AMPK as a mediator of hormonal signalling. J Mol Endocrinol. 2010;44:87-97. doi: 10.1677/JME-09-0063

 

  1. Rosso P, Fioramonti M, Fracassi A, et al. AMPK in the central nervous system: Physiological roles and pathological implications. Res Rep Biol. 2016;7:1-13. doi: 10.2147/RRB.S90858

 

  1. Kola B, Boscaro M, Rutter GA, Grossman AB, Korbonits M. Expanding role of AMPK in endocrinology. Trends Endocrinol Metab. 2006;17:205-215. doi: 10.1016/j.tem.2006.05.006

 

  1. Kola B, Hubina E, Tucci SA, et al. Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase. J Biol Chem. 2005;280:25196-25201. doi: 10.1074/jbc.C500175200

 

  1. Wittmann G, Deli L, Kalló I, et al. Distribution of type 1 cannabinoid receptor (CB1)-immunoreactive axons in the mouse hypothalamus. J Comp Neurol. 2007;503:270-279. doi: 10.1002/cne.21383

 

  1. Cota D, Marsicano G, Tschöp M, et al. The endogenous cannabinoid system affects energy balance via central orexigenic drive and peripheral lipogenesis. J Clin Invest. 2003;112:423-431. doi: 10.1172/JCI17725

 

  1. Christ-Crain M, Kola B, Lolli F, et al. AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: A novel mechanism in Cushing’s syndrome. FASEB J. 2008;22:1672-1683. doi: 10.1096/fj.07-094144

 

  1. Hiley CR, Ford WR. Cannabinoid pharmacology in the cardiovascular system: Potential protective mechanisms through lipid signalling. Biol Rev Camb Philos Soc. 2004;79:187-205. doi: 10.1017/s1464793103006201

 

  1. Kirkham TC, Williams CM, Fezza F, Di Marzo V. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: Stimulation of eating by 2-arachidonoyl glycerol. Br J Pharmacol. 2002;136:550-557. doi: 10.1038/sj.bjp.0704767

 

  1. Di Marzo V, Goparaju SK, Wang L, et al. Leptin-regulated endocannabinoids are involved in maintaining food intake. Nature. 2001;410:822-825. doi: 10.1038/35071088

 

  1. Bullón P, Alcocer-Gómez E, Carrión AM, et al. AMPK phosphorylation modulates pain by activation of NLRP3 inflammasome. Antioxid Redox Signal. 2016;24:157-170. doi: 10.1089/ars.2014.6120

 

  1. Russe OQ, Möser CV, Kynast KL, et al. Activation of the AMP-activated protein kinase reduces inflammatory nociception. J Pain. 2013;14:1330-1340. doi: 10.1016/j.jpain.2013.05.012

 

  1. Sun LJ, Yu JW, Wan L, Zhang XY, Shi YG, Chen MY. Endocannabinoid system activation contributes to glucose metabolism disorders of hepatocytes and promotes hepatitis C virus replication. Int J Infect Dis. 2014;23:75-81. doi: 10.1016/j.ijid.2013.12.017

 

  1. Borgquist A, Meza C, Wagner EJ. The role of AMP-activated protein kinase in the androgenic potentiation of cannabinoid-induced changes in energy homeostasis. Am J Physiol Endocrinol Metab. 2015;308:E482-E495. doi: 10.1152/ajpendo.00421.2014

 

  1. Hanus L, Avraham Y, Ben-Shushan D, Zolotarev O, Berry EM, Mechoulam R. Short-term fasting and prolonged semistarvation have opposite effects on 2-AG levels in mouse brain. Brain Res. 2003;983:144-151. doi: 10.1016/s0006-8993(03)03046-4

 

  1. Rosen ED, Spiegelman BM. Adipocytes as regulators of energy balance and glucose homeostasis. Nature. 2006;444:847-853. doi: 10.1038/nature05483

 

  1. Cristino L, Luongo L, Imperatore R, et al. Orexin-A and endocannabinoid activation of the descending antinociceptive pathway underlies altered pain perception in leptin signaling deficiency. Neuropsychopharmacology. 2016;41:508-520. doi: 10.1038/npp.2015.173

 

  1. King-Himmelreich TS, Möser CV, Wolters MC, et al. AMP-activated kinase and the endogenous endocannabinoid system might contribute to antinociceptive effects of prolonged moderate caloric restriction in mice. Mol Pain. 2017;13:1744806917703111. doi: 10.1177/1744806917703111
Share
Back to top
INNOSC Theranostics and Pharmacological Sciences, Electronic ISSN: 2705-0823 Print ISSN: 2705-0734, Published by AccScience Publishing
We use cookies on our website to ensure you get the best experience.
Read more about our cookies here
Accept