High-fat meals reduce 24-h circulating leptin concentrations in women

Leptin induces weight loss in rodents via its effects on food intake and en ergy expenditure. nigh-fat diets induce weight gain, but the mechanism is n ot well understood. Previous studies have not found an effect of dietary fa t content on fasting leptin. There is a nocturnal increase of leptin, howev er, which is related to insulin responses to meals. We have reported that a dipocyte glucose utilization is involved in insulin-induced leptin secretio n in vitro. Accordingly, high-fat, low-carbohydrate (HF/LC) meals, which in duce smaller insulin and glucose responses, would produce lower leptin conc entrations than low-fat, high-carbohydrate (LF/HC) meals. Blood samples wer e collected every 30-60 min for 24 h from 19 normal-weight (BMI, 24,2 +/- 0 .7 kg/m(2); percent body fat; = 31 +/- 1%) women on 2 days (10 days apart) during which the subjects were randomized to consume three isocaloric 730-k cal meals containing either 60/20 or 20/60% of energy as fat/carbohydrate, Overall insulin and glycemic responses (24-h area under the curve [AUC]) we re reduced by 55 and 61%, respectively, on the HF/LC day (P < 0.0001). Duri ng LF/RC feeding, there mere larger increases of leptin 4-6 h after breakfa st (38 +/- 7%, P < 0.001) and lunch (78 +/- 14%, P < 0.001) than after HF/L C meals (both P < 0.02). During LF/HC: feeding, leptin increased from a mor ning baseline of 10.7 +/- 1.6 ng/ml to a nocturnal peak of 21.3 +/- 1.3 ng/ ml (change, 10.6 +/- 1.3 ng/ml; percent change, 123 +/- 16%; P < 0.0001), T he! amplitudes of the nocturnal rise of leptin and the 24-h leptin AUC were 21 +/- 8% (P < 0.005) and 38 +/- 12% (P < 0.0025) larger,respectively, on the LF/HC day. In summary, consumption of HF/LC meals results in lowered 24 -h circulating leptin concentrations. This result may be a consequence of d ecreased adipocyte glucose metabolism. Decreases of 24-h circulating leptin could contribute to the weight gain during consumption of high-fat diets.