Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator
- PMID: 38356211
- PMCID: PMC10901667
- DOI: 10.3803/EnM.2024.1922
Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator
Abstract
5´-Adenosine monophosphate (AMP)-activated protein kinase (AMPK), a cellular energy sensor, is an essential enzyme that helps cells maintain stable energy levels during metabolic stress. The hypothalamus is pivotal in regulating energy balance within the body. Certain neurons in the hypothalamus are sensitive to fluctuations in food availability and energy stores, triggering adaptive responses to preserve systemic energy equilibrium. AMPK, expressed in these hypothalamic neurons, is instrumental in these regulatory processes. Hypothalamic AMPK activity is modulated by key metabolic hormones. Anorexigenic hormones, including leptin, insulin, and glucagon-like peptide 1, suppress hypothalamic AMPK activity, whereas the hunger hormone ghrelin activates it. These hormonal influences on hypothalamic AMPK activity are central to their roles in controlling food consumption and energy expenditure. Additionally, hypothalamic AMPK activity responds to variations in glucose concentrations. It becomes active during hypoglycemia but is deactivated when glucose is introduced directly into the hypothalamus. These shifts in AMPK activity within hypothalamic neurons are critical for maintaining glucose balance. Considering the vital function of hypothalamic AMPK in the regulation of overall energy and glucose balance, developing chemical agents that target the hypothalamus to modulate AMPK activity presents a promising therapeutic approach for metabolic conditions such as obesity and type 2 diabetes mellitus.
Keywords: AMP-activated protein kinases; Energy metabolism; Glucose metabolism; Hormones; Hypothalamus.
Conflict of interest statement
No potential conflict of interest relevant to this article was reported.
Figures
![Fig. 1.](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/10901667/bin/enm-2024-1922f1.gif)
Similar articles
-
Hypothalamic AMPK as a Mediator of Hormonal Regulation of Energy Balance.Int J Mol Sci. 2018 Nov 11;19(11):3552. doi: 10.3390/ijms19113552. Int J Mol Sci. 2018. PMID: 30423881 Free PMC article. Review.
-
PAS kinase is a nutrient and energy sensor in hypothalamic areas required for the normal function of AMPK and mTOR/S6K1.Mol Neurobiol. 2014 Oct;50(2):314-26. doi: 10.1007/s12035-013-8630-4. Epub 2014 Jan 21. Mol Neurobiol. 2014. PMID: 24445950
-
Glucagon-like peptide 1 (GLP-1) can reverse AMP-activated protein kinase (AMPK) and S6 kinase (P70S6K) activities induced by fluctuations in glucose levels in hypothalamic areas involved in feeding behaviour.Mol Neurobiol. 2012 Apr;45(2):348-61. doi: 10.1007/s12035-012-8239-z. Epub 2012 Feb 5. Mol Neurobiol. 2012. PMID: 22311299
-
AMPK and the neuroendocrine regulation of appetite and energy expenditure.Mol Cell Endocrinol. 2013 Feb 25;366(2):215-23. doi: 10.1016/j.mce.2012.06.012. Epub 2012 Jul 9. Mol Cell Endocrinol. 2013. PMID: 22789749 Review.
-
AMP-activated protein kinase plays a role in the control of food intake.J Biol Chem. 2004 Mar 26;279(13):12005-8. doi: 10.1074/jbc.C300557200. Epub 2004 Jan 23. J Biol Chem. 2004. PMID: 14742438
References
-
- Schneeberger M, Gomis R, Claret M. Hypothalamic and brainstem neuronal circuits controlling homeostatic energy balance. J Endocrinol. 2014;220:T25–46. - PubMed
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Medical