Selective release of gastrointestinal hormones induced by an orally active GPR39 agonist.

Objectives: Obesity is a complex disease associated with a high risk of comorbidities. Gastric bypass surgery, an invasive procedure with low patient eligibility, is currently the most effective intervention that achieves sustained weight loss. This beneficial effect is attributed to alterations in gut hormone signaling.

Fasting- and ghrelin-induced food intake is regulated by NAMPT in the hypothalamus.

Aim: Neurons in the arcuate nucleus of the hypothalamus are involved in regulation of food intake and energy expenditure, and dysregulation of signalling in these neurons promotes development of obesity. The role of the rate-limiting enzyme in the NAD salvage pathway, nicotinamide phosphoribosyltransferase (NAMPT), for regulation energy homeostasis by the hypothalamus has not been extensively studied.

Methods: We determined whether Nampt mRNA or protein levels in the hypothalamus of mice were affected by diet-induced obesity, by fasting and re-feeding, and by leptin and ghrelin treatment.

Translating biased signaling in the ghrelin receptor system into differential in vivo functions.

Biased signaling has been suggested as a means of selectively modulating a limited fraction of the signaling pathways for G-protein-coupled receptor family members. Hence, biased ligands may allow modulation of only the desired physiological functions and not elicit undesired effects associated with pharmacological treatments. The ghrelin receptor is a highly sought antiobesity target, since the gut hormone ghrelin in humans has been shown to increase both food intake and fat accumulation.

Pannexin-2-deficiency sensitizes pancreatic β-cells to cytokine-induced apoptosis in vitro and impairs glucose tolerance in vivo.

Pannexins (Panx's) are membrane proteins involved in a variety of biological processes, including cell death signaling and immune functions. The role and functions of Panx's in pancreatic β-cells remain to be clarified. Here, we show Panx1 and Panx2 expression in isolated islets, primary β-cells, and β-cell lines.

Dietary non-esterified oleic Acid decreases the jejunal levels of anorectic N-acylethanolamines.

Background And Aims: Oleoylethanolamide and several other N-acylethanolamines (NAEs), e.g. linoleoylethanolamide and palmitoylethanolamide, have anorectic properties in rats, and prolonged intake of a high-fat diet decreases the levels of the anorectic NAEs in jejunum.

N-acylation of phosphatidylethanolamine and its biological functions in mammals.

N-acylphosphatidylethanolamine (NAPE) and N-acylplasmenylethanolamine (pNAPE) are widely found phospholipids, and they are precursors for N-acylethanolamines, a group of compounds that has a variety of biological effects and encompasses the endocannabinoid anandamide. NAPE and pNAPE are synthesized by the transfer of an acyl chain from a donor phospholipid, to the amine in phosphatidylethanolamine or plasmenylethanolamine. NAPE has been reported to stabilize model membranes during brain ischemia, and to modulate food intake in rodents, thus having bioactive effects besides its precursor role.

2-Oleoyl glycerol is a GPR119 agonist and signals GLP-1 release in humans.

Objective: Dietary fat is thought to stimulate release of incretin hormones via activation of fatty acid receptors in the intestine. However, dietary fat (triacylglycerol) is digested to 2-monoacylglycerol and fatty acids. Activation of G protein-coupled receptor 119 (GPR119) stimulates glucagon-like peptide-1 (GLP-1) release from the intestinal L-cells.

Studies on the anorectic effect of N-acylphosphatidylethanolamine and phosphatidylethanolamine in mice.

N-acyl-phosphatidylethanolamine is a precursor phospholipid for anandamide, oleoylethanolamide, and other N-acylethanolamines, and it may in itself have biological functions in cell membranes. Recently, N-palmitoyl-phosphatidylethanolamine (NAPE) has been reported to function as an anorectic hormone secreted from the gut and acting on the brain (Gillum et al., [5]).

Dietary fat decreases intestinal levels of the anorectic lipids through a fat sensor.

This study was undertaken to investigate the link between dietary fat content and intestinal levels of anorectic N-acylethanolamines (NAEs), including oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA). Male rats were fed high-fat diets (HFDs) with variable percentages of fat [20-45% of total energy (E%)] for 1-7 d; afterward, the jejunums were isolated, and jejunal NAE levels were measured by liquid-chromatography mass spectrometry. Enzyme activities and mRNA expression levels were measured for two synthesizing enzymes, N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD) and glycerophosphodiesterase (GDE1), and one degrading enzyme, fatty acid amide hydrolase (FAAH).

The endocannabinoid system and its relevance for nutrition.

Endocannabinoids bind to cannabinoid, vanilloid, and peroxisome proliferator-activated receptors. The biological actions of these polyunsaturated lipids are controlled by key agents responsible for their synthesis, transport and degradation, which together form an endocannabinoid system (ECS). In the past few years, evidence has been accumulated for a role of the ECS in regulating food intake and energy balance, both centrally and peripherally.

N-acylethanolamines, anandamide and food intake.

Anandamide and the other N-acylethanolamines, e.g. oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and linoleoylethanolamide (LEA), may be formed by several enzymatic pathways from their precursors, which are the N-acylated ethanolamine phospholipids.