Hypothalamic AMPK as a Mediator of Hormonal Regulation of Energy Balance

Abstract

As a cellular energy sensor and regulator, adenosine monophosphate (AMP)-activated protein kinase (AMPK) plays a pivotal role in the regulation of energy homeostasis in both the central nervous system (CNS) and peripheral organs. Activation of hypothalamic AMPK maintains energy balance by inducing appetite to increase food intake and diminishing adaptive thermogenesis in adipose tissues to reduce energy expenditure in response to food deprivation. Numerous metabolic hormones, such as leptin, adiponectin, ghrelin and insulin, exert their energy regulatory effects through hypothalamic AMPK via integration with the neural circuits. Although activation of AMPK in peripheral tissues is able to promote fatty acid oxidation and insulin sensitivity, its chronic activation in the hypothalamus causes obesity by inducing hyperphagia in both humans and rodents. In this review, we discuss the role of hypothalamic AMPK in mediating hormonal regulation of feeding and adaptive thermogenesis, and summarize the diverse underlying mechanisms by which central AMPK maintains energy homeostasis.

Activation of AMPK under Hypoxia: Many Roads Leading to Rome

“…The protective effects of AMPK have been considered in the context of several hormones that might be associated with (systemic) energy depletion or inflammatory stimuli. The "hunger hormone" ghrelin has been considered to be protective in ischemia/reperfusion injury and has been shown to activate AMPK [87,88], probably via CaMKK2 [89]. Also, leptin signaling, which basically acts antagonistic to ghrelin, has been reported to activate AMPK in chronic intermittent hypoxia independently of AMP levels in peripheral tissues like skeletal muscle [13,64,90], whereas it exerts an inhibitory effect on hypothalamic AMPK [91,92].…”

Neuroendocrine Control, Inflammation, and Psychological Aspects After Interdisciplinary Therapy in Obese Women

“…The stimulatory effect of AgRP is inhibited by α-MSH. The melanocortin system, which participates in the α-MSH neuropeptide stimulation in the hypothalamus, is considered of paramount importance in the regulation of energy metabolism and body weight [38][39][40][41]. Despite of the correlation there is no significant result between body weight and α-MSH, the increase of this neuropeptide suggests modulation of the state of hyperleptinemia, as a key hormone for central and peripheral energy balance control [39,40].…”

How treatments with endocrine and metabolic drugs influence pituitary cell function

“…AMPK activity has a role in tuning orexigenic signals during fasting and during refeeding and in mediating the regulatory effects of multiple peripheral hormones (GLP-1, oxyntomodulin, ghrelin, leptin, adiponectin and insulin) on food intake and energy expenditure. In summary, hypothalamic AMPK has a role in integrating peripheral signals with neural circuits, and its high activation is related to increased food intake and decreased thermogenesis as adaptive changes to calorie restriction whereas low activation is related to refeeding and increased energy expenditure (9,10). To our knowledge, no data have been reported on a possible role of hypothalamic AMPK in regulating the activity of GHRHand somatostatin neurons in the context of the interplay between GH axis and energy homeostasis.…”

“…glucose) sensor and to mediate the regulatory effects of hormones (leptin, ghrelin, insulin, adiponectin, GLP-1) on energy homeostasis. In summary, hypothalamic AMPK has a role in integrating peripheral signals with neural circuits, and its activation is related to increased food intake and decreased thermogenesis as adaptive changes to calorie restriction (9,10,11). In the last 10 years, evidence has accumulated that AMPK plays also a role in the interplay between the activity of neuroendocrine axes and energy homeostasis at both hypothalamic and pituitary level.…”