Adipogenic and orexigenic effects of the ghrelin-receptor ligand tabimorelin are diminished in leptin-signalling-deficient ZDF rats.

OBJECTIVE: The aim was to investigate the possible interactions of the two peripheral hormones, leptin and ghrelin, that regulate the energy balance in opposite directions. METHODS: Leptin-receptor mutated Zucker diabetic fatty (ZDF) and lean control rats were treated with the ghrelin-receptor ligand, tabimorelin (50 mg/kg p.o.) for 18 days, and the effects on body weight, food intake and body composition were investigated. The level of expression of anabolic and catabolic neuropeptides and their receptors in the hypothalamic area were analysed by in situ hybridization. RESULTS: Tabimorelin treatment induced hyperphagia and adiposity (increased total fat mass and gain in body weight) in lean control rats, while these parameters were not increased in ZDF rats. Treatment with tabimorelin of lean control rats increased hypothalamic mRNA expression of the anabolic neuropeptide Y (NPY) mRNA and decreased hypothalamic expression of the catabolic peptide pro-opiomelanocortin (POMC) mRNA. In ZDF rats, the expression of POMC mRNA was not affected by treatment with tabimorelin, whereas NPY mRNA expression was increased in the hypothalamic arcuate nucleus. CONCLUSION: This shows that tabimorelin-induced adiposity and hyperphagia in lean control rats are correlated with increased hypothalamic NPY mRNA and decreased POMC mRNA expression. The elimination of tabimorelin-induced adiposity and hyperphagia in ZDF rats may be due to lack of POMC mRNA downregulation. In conclusion, we suggest that ghrelin-receptor ligands exert their adipogenic and orexigenic effects via hypothalamic mechanisms that are dependent on intact leptin-receptor signalling.

The proglucagon-derived peptide, glucagon-like peptide-2, is a neurotransmitter involved in the regulation of food intake.

The dorsomedial hypothalamic nucleus harbors leptin sensitive neurons and is intrinsically connected to hypothalamic nuclei involved in feeding behavior. However, it also receives ascending input from the visceroceptive neurons of the brainstem. We have identified a unique glucagon-like-peptide-2 containing neuronal pathway connecting the nucleus of the solitary tract with the dorsomedial hypothalamic nucleus. A glucagon-like-peptide-2 fiber plexus targets neurons expressing its receptor within the dorsomedial hypothalamic nucleus. Pharmacological and behavioral studies confirmed that glucagon-like-peptide-2 signaling is a specific transmitter inhibiting rodent feeding behavior and with potential long-term effects on body weight homeostasis. The glucagon-like-peptide-1 receptor antagonist, Exendin (9-39) is also a functional antagonist of centrally applied glucagon-like-peptide-2.

The dietary fatty acids of patients with coronary artery disease and control in Curacao: implications for primary and secondary prevention

Patients with coronary artery diseases are advised to augment their dietary linoleic acid intakes at the expense of saturated fatty acids. We investigated whether the dietary linoleic acid intake of 57 patients with coronary artery disease (47 males, 10 females; ages 61 ñ 10 years) in Curacao is higher as compared with 77 controls (51 males, 26 females; ages 56 ñ 7 years). For this, we measured plasma cholesterol ester fatty acids, which reflect the dietary fatty acid composition of the preceeding weeks. Patients with coronary artery disease and controls had minor differences in cholesterol ester fatty acids. Their cholesterol ester linoleic acid content suggests that the dietary polyunsaturated/saturated fatty acid ratio is far below 1. Comparison with data reported for the the Netherlands, Greenland and Crete showed that the dietary fatty acid composition in Curacao is typically Western with a high intake of saturated fatty acids, a low intake of monounsaturated fatty acids and the consumption of linoleic acid as the predominant polyunsaturated fatty acid. Intake of long chain polyunsaturated fatty acids from fatty fish is low. Reduction of dietary saturated fatty acids, augmentation of fish consumption, and an increase of the Ó-linolenic/linoleic acid ratio are likely to be of benefit to both primary and secondary prevention from coronary artery disease in Curaco.

The dietary fatty acids of patients with coronary artery disease and control in Curacao: implications for primary and secondary prevention

Patients with coronary artery diseases are advised to augment their dietary linoleic acid intakes at the expense of saturated fatty acids. We investigated whether the dietary linoleic acid intake of 57 patients with coronary artery disease (47 males, 10 females; ages 61 ñ 10 years) in Curacao is higher as compared with 77 controls (51 males, 26 females; ages 56 ñ 7 years). For this, we measured plasma cholesterol ester fatty acids, which reflect the dietary fatty acid composition of the preceeding weeks. Patients with coronary artery disease and controls had minor differences in cholesterol ester fatty acids. Their cholesterol ester linoleic acid content suggests that the dietary polyunsaturated/saturated fatty acid ratio is far below 1. Comparison with data reported for the the Netherlands, Greenland and Crete showed that the dietary fatty acid composition in Curacao is typically Western with a high intake of saturated fatty acids, a low intake of monounsaturated fatty acids and the consumption of linoleic acid as the predominant polyunsaturated fatty acid. Intake of long chain polyunsaturated fatty acids from fatty fish is low. Reduction of dietary saturated fatty acids, augmentation of fish consumption, and an increase of the O-linolenic/linoleic acid ratio are likely to be of benefit to both primary and secondary prevention from coronary artery disease in Curaco.(AU)