The brain: a new organ for the metabolic actions of SIRT1.

The sirtuins are a family of highly conserved nicotine adenine dinucleotide (NAD+)-dependent deacetylases that act as cellular sensors to detect energy availability and regulate metabolic processes. Sirtuin 1 (SIRT1) is one of the family members that is activated in response to caloric restriction, acting on multiple targets in a wide range of tissues. Recent studies have shown that SIRT1 controls glucose and lipid metabolism in both liver and muscle, promotes fat mobilization, stimulates remodeling of white to brown fat, controls insulin secretion in the pancreas, and senses nutrient availability in the hypothalamus. SIRT1 is located in several areas of the brain and its central metabolic actions have attracted much attention in the last decade. In this short review, we summarize the main actions and molecular pathways triggered by SIRT1 that control feeding behavior, energy expenditure, glucose metabolism, and insulin sensitivity, with an emphasis on the emerging role of SIRT1 in the brain.

Macronutrients act directly on the stomach to regulate gastric ghrelin release.

BACKGROUND: Ghrelin is a gastric secreted hormone deeply implicated in meal initiation and body weight regulation. This peptide is a peripheral orexigenic hormone with a nutritional status-dependent regulation showing a pre-pandrial rise and post-prandial fall pattern. A wide variety of studies have tested the effect of meal different nutrient composition over stomach mucosa ghrelin content and plasmatic ghrelin levels; nevertheless, few and non-conclusive data exist about the direct action of macronutrients on the stomach in order to regulate ghrelin secretion. The recent identification of taste receptors or chemoreceptors in the stomach mucosa would reinforce this paradigm. AIMS: To investigate the individual effect of different macronutrients (l-glutamine, lipids, and glucose) over gastric ghrelin secretion by using an in vitro gastric explants model. RESULTS: L-glutamine and intralipid emulsion act locally in the stomach decreasing ghrelin secretion, while no effect was found after glucose exposure. CONCLUSIONS: These results show for the first time that macronutrients, and specially amino acids and lipids, act directly in the stomach in order to regulate gastric ghrelin release. Consequently, the chemosensory capacity of the stomach, until now restricted to the oral cavity or intestine, is demonstrated.

Peripheral endocannabinoid system-mediated actions of rimonabant on growth hormone secretion are ghrelin-dependent.

The somatotroph axis is a crucial pathway regulating metabolism. Despite the fact that the endocannabinoid system has been also revealed as a potent modulator of energy homeostasis, little information is available concerning a putative interaction between these two systems. The aim of the present study was to determine the in vivo effects of the blockade of the cannabinoid receptor type 1 (CB1) over growth hormone (GH) secretion using the CB1 antagonist rimonabant. The results obtained show that the blockade of the CB1 peripheral receptor by i.p. injection of rimonabant significantly inhibited pulsatile GH secretion. Similarly, it was found that this injection significantly decreased ghrelin-induced GH secretion without any effect on growth hormone-releasing hormone (GHRH)-induced GH discharge. In situ hybridisation showed that the peripheral blockade of CB1 did not affect hypothalamic somatostatin mRNA levels; however, GHRH mRNA expression was significantly decreased. The blockade of the vagus nerve signal by surgical vagotomy eliminated the inhibitory action of rimonabant on GHRH mRNA and consequently on GH. On the other hand, the central CB1 blockade by i.c.v. rimonabant treatment was unable to reproduce the effect of peripheral blockade on GHRH mRNA, nor the GH response to ghrelin. In conclusion, the data reported in the present study establish, from a physiological point of view, the existence of a novel mechanism of GH regulation implicating the action of the cannabinoid receptor on the somatotroph axis.

[Role of ghrelin in the pathophysiology of eating behaviour]. / Papel de la ghrelina en la fisiopatología del comportamiento alimentario.

Ghrelin, the endogenous ligand for GHS-R, was isolated from rat stomach, although other tissues exist expressing ghrelin, such as pituitary, hypothalamus, placent, ovary, testes, etc. It was showed that ghrelin is implicated in GH secretion, in vivo and in vitro. There are direct evidences that proof that ghrelin administration induces GH secretion. There are in vivo data, showing ghrelin as a most potent GH secretor than GHRH. Evidences exist of ghrelin actions in the regulation of food intake and energy homeostasis. Ghrelin has a clear role in the differents pathologies such as obesity, anorexia and bulimia.