Sunday, 7 August 2011

Brain control of fat metabolism

Brain insulin controls adipose tissue lipolysis and lipogenesis.

"Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis"

"Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality."

Hypothalamic control of lipid metabolism: focus on leptin, ghrelin and melanocortins.

"In mammals, neurons, particularly in the arcuate nucleus of the hypothalamus (ARC), are involved in the regulation of energy homeostasis. One regulatory pathway consists of neurons co-expressing neuropeptide Y (NPY) and agouti-related protein (AgRP), both potent stimulators of food intake, and an adjacent set of ARC neurons co-express proopiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART), which suppress food intake."

"The anorectic effect of these drugs requires the accumulation of malonyl-CoA in the hypothalamus, which may be sensed as a signal of nutrient abundance by critical neurons regulating food intake (‘malonyl-CoA hypothesis’) and decreased expression of orexigenic (AgRP and NPY) and elevated expression of anorexigenic (CART, POMC) neuropeptides in the ARC"

"Leptin induces opposite effects on two ARC neuronal subpopulations: it directly inhibits the orexigenic NPY/AgRP-containing neurons and it stimulates the electrical activity of anorexigenic POMC neurons"

"One of the factors required by leptin to exert its anorectic effect is hypothalamic AMPK"

"suppression of AMPK activity in the medial hypothalamus is necessary for leptin’s anorexic and weight loss effects and that lack of suppression causes leptin resistance"

"The most relevant receptors in terms of energy balance regulation are MC3R and MC4R. Receptor agonist delivery into the hypothalamus reduces food intake, body weight and fat mass"

"Anatomical studies have demonstrated that central WAT sympathetic outflow neurons express MC4R"

" Central melanocortins modulate the norepinephrine turnover, which is the principal initiator of lipolysis in mammals. Norepinephrine is released from the sympathetic nerves innervating WAT, and the central injection of a MC3/4R agonist increased the norepinephrine turnover in specific fat depots"

Overall this is a very good study and needs to read in its entirety.

Hyperphagia and increased fat accumulation in two models of chronic CNS glucagon-like peptide-1 loss of function.

More evidence for the power of GLP-1 in obesity.

"Collectively, these data provide the strongest evidence to date that CNS GLP-1 plays a physiologic role in the long-term regulation of energy balance. Moreover, they suggest that this role is distinct from that of circulating GLP-1 as a short-term satiation signal."

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