Alcohol and the effect on some appetite-regulating hormones in man

Abstract: Beverage containing alcohol has been used for centuries to stimulate appetite. Ingestion of a moderate amount of alcohol increase energy intake. Regulation of food intake is complex. Several factors cooperate such as neural impulses from sensory organs; sight, smell, gut distension, social setting, memory, current energy status and hormones. How alcohol affects these factors is not well understood. This research project has focused on how alcohol influences the peripheral secretion of hormones, known to convey information from the periphery to hunger-regulating centers in the brain about the prevailing caloric homeostasis. Leptin produced by adipocytes - and gut-derived peptide YY (PYY) are two such hormones which inhibit food intake, whereas ghrelin produced by cells in the upper part of the gastro intestinal tract - stimulates appetite. These hormones have central effects on hypothalamic neuropeptide Y (NPY) and on pro-opiomelanocortin (POMC) which stimulates and down-regulates hunger, respectively. Other gut hormones, having central effects as well as influence on intestinal motility, are glucagon-like peptide (GLP-1) and obestatin. Liver derived insulin-like growth factor-1 (IGF-1) and its binding protein insulin-like growth factor binding protein-1 (IGFBP-1) are also of interest in this context, as they are affected by nutritional status and could be factors which influence appetite-regulating centers directly or indirectly via peripherally produced hormones. Aim: To study the effect of alcohol on the secretion of peripheral hormones known to be involved in the regulation of food intake. Material and Methods: 51 healthy subjects (26F/25M) were included in the study. All were young, healthy, normal weight and free of medication. In five separate experiments subjects were investigated in groups of 7 12 individuals. In exp 1, 2 and 3 the effect of alcohol on various hormone levels in serum, was compared with the effect of drinking water. In exp 2 the alcohol effect on urinary excretion of catecholamines was determined with or without oral beta-receptor blockade (propranolol). In exp 5 alcohol influence on gastro-intestinal hormones was investigated with or without sucralfate gastroprotection. Results and discussion: A moderate amount of alcohol induced a significant inhibition of both diurnal and nocturnal secretion of leptin. Factors known to affect the secretion of leptin such as insulin, glucose, cortisol, testosterone, and catecholamines were not influenced by the drug. IGFBP-1 increased significantly after alcohol, contrasting IGF-1, which remained unchanged. This resulted in a low IGF-1/IGFBP-1 ratio and, as a consequence, in a decreased IGF-1 bioavailability. Alcohol had both acute and prolonged inhibitory effect on serum levels of both total and octanoylated ghrelin, but was without significant influence on serum concentrations of NPY, PYY, GLP-1 and obestatin. Gastro-protection with sucralfate did not change the alcohol-induced inhibition of leptin and ghrelin secretion. Conclusion: Acute ingestion of alcohol inhibits the secretion of leptin and ghrelin, induces a marked decline in the IGF-1/IGFBP-1 ratio, but leaves NPY, PYY, GLP-1 and obestatin unchanged. Previous studies suggest that leptin may have long-term rather than acute inhibitory effects on hunger. Therefore, the present findings do not lend strong support to the hypothesis that alcohol has acute stimulatory effect on appetite by influencing peripherally produced hormones. If alcohol has appetite-stimulating properties in humans it is more likely that this is an effect caused by direct influence on appetite-regulating neurons in the brain.