Effects of exogenous leptin on satiety and satiation in patients with lipodystrophy and leptin insufficiency.

To examine leptin's role in human appetite regulation, we studied recombinant methionyl human leptin's effects on satiation and satiety in a model of leptin insufficiency, lipodystrophy. Eight females with hypoleptinemia and lipodystrophy were given sc injections of A-100 (maximal dose, 200% of that predicted to normalize serum leptin) for 4 months. Satiation and satiety were determined before and again during leptin treatment. Satiation was measured as the time to voluntary cessation of eating from a standardized food array after a 12-h fast. Satiety was determined as the time to hunger sufficient to consume a full meal after consumption of a standardized preload. During leptin treatment, satiation time decreased (41.2 +/- 18.2 to 19.5 +/- 10.6 min; P = 0.01), satiety time increased (62.9 +/- 64.8 to 137.8 +/- 91.6 min; P = 0.04), energy consumed to produce satiation decreased (2034 +/- 405 to 1135 +/- 432 kcal or 8.5 +/- 1.7 to 4.7 +/- 1.8 MJ; P < 0.01), and the amount of food desired in the postabsorptive state decreased (P < 0.02). Ghrelin concentrations also decreased during leptin administration (284.3 +/- 127.9 to 140.6 +/- 104.5 pmol/liter; P < 0.002). We conclude that increased leptin in patients with lipodystrophy results in less caloric, shorter, more satiating meals and longer-lived satiety. These data support the hypothesis that leptin plays an important, permissive role in human appetite regulation.

Long-term abstinent alcoholics have a blunted blood glucose response to 2-Deoxy-d-glucose.

AIMS: In this study we explored the relationship between alcohol and carbohydrate consumption in long-term abstinent alcoholics. METHODS: We employed an established laboratory paradigm which allowed us to stimulate and measure dietary intake. 2-Deoxy-d-glucose (2-DG) is a glucose analogue that causes an intracellular energy deprivation resulting in exaggerated food consumption and a compensatory metabolic response to raise blood glucose. Using a double-blind design, we gave an infusion of 25 mg/kg 2-DG or placebo to 20 long-term abstinent alcoholics and 19 healthy volunteers. RESULTS: There were no baseline differences in any dietary, behavioural or biochemical variables. As expected, 2-DG increased caloric consumption and blood glucose levels in a time-dependent fashion. There were no differences in food consumption between the alcoholics and the healthy volunteers following the 2-DG stimulus. However, the alcoholic group had a significantly blunted response in blood glucose. CONCLUSIONS: The origin of this atypical blood glucose response may antedate the onset of alcoholism, or it may be secondary to alcohol-related damage that persists beyond 6 months. Previous accounts of increased sweet consumption in alcoholics were not substantiated, although they may be present in the peri-withdrawal period.