Hypothalamic Regulation of Appetite

Katherine A. Simpson; Niamh M. Martin; Steve R. Bloom


Expert Rev Endocrinol Metab. 2008;3(5):577-592. 

In This Article

Nutrient Sensing

There is evidence that the hypothalamus can also sense nutrients and adjust food intake accordingly.[209] When cellular energy stores are deplete, the enzyme AMPK is activated in order to increase substrate uptake.[210] In the ARC, activation of AMPK leads to increased food intake and bodyweight; an effect that is inhibited by both insulin and leptin.[153] However, hypothalamic AMPK inhibition is essential for leptin's effect on food intake and bodyweight.[153] Recent evidence shows that ghrelin activates NPY neurons in the ARC through an AMPK pathway.[211] AMPK in the VMN also appears to play a key role in the detection of acute hypoglycemia and initiation of the glucose counter-regulatory response.[212] There has also been increasing evidence for a common pathway within the PVN involving AMPK. Intraperitoneal leptin and lateral ventricle administration of a melanocortin agonist causes a significant decrease in AMPK activity in the PVN,[153] whereas ICV AgRP causes an increase.

There are considerable data demonstrating the effects of circulating carbohydrates, lipids and amino acids in the hypothalamic control of appetite. Hypoglycemia itself stimulates food intake and the hypothalamus has key glucose-sensing neurons in order to counteract this.[213] Interestingly, acute hypoglycemia increases hypothalamic NPY and AgRP and reduces POMC expression.[214] Plasma long-chain fatty acids cross the blood-brain barrier in a dose-dependent manner and can regulate food intake via the hypothalamus. ICV administration of the long-chain fatty acid oleic acid inhibits food intake by reduction of ARC AgRP and NPY expression.[215] Amino acids are also implicated in the hypothalamic regulation of food intake, and ICV administration of the amino acid leucine reduces food intake in rats. Leucine is thought to mediate its effect through increased hypothalamic mTOR activity that reduces ARC NPY expression.[154] Intestinal chemosensors are an exciting recent area of focus in understanding feed-forward signals to the hypothalamus to regulate energy intake.[216]


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.