Endocrinol Metab.  2024 Feb;39(1):1-11. 10.3803/EnM.2024.1922.

Hypothalamic AMP-Activated Protein Kinase as a Whole-Body Energy Sensor and Regulator

• Min SH
• Song DK
• Lee CH
• Roh E
• Kim MS

• KMID: 2552790
• DOI: http://doi.org/10.3803/EnM.2024.1922

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.

Keyword

AMP-activated protein kinases; Hypothalamus; Energy metabolism; Glucose metabolism; Hormones

Figure

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  Fig. 1. The regulators and conditions that alter hypothalamic 5´-adenosine monophosphate-activated protein kinase (AMPK) activity and their associated physiological outcomes. (A) Conditions and regulators inducing hypothalamic AMPK activation. (B) Conditions and regulators inducing hypothalamic AMPK inactivation. GLP-1, glucagon-like peptide-1; SNS, sympathetic nervous system; BAT, brown adipose tissue.

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