Leptin administration induces weight loss in rodents via its effects on food intake and energy expenditure. High fat/low carbohydrate (HF/LC) diets induce weight gain in humans and animals, but the mechanism is not well understood. In humans, there is a nocturnal increase of plasma leptin concentrations which is related to insulin responses to meals, but this increase does not occur in fasted subjects. We have recently reported that adipocyte glucose uptake and metabolism are important determinants of insulin-induced leptin secretion in vitro (Endocrinology 139:551-558, 1998). Accordingly, HC/LF meals, which induce greater excursions of circulating insulin and glucose, should produce higher leptin concentrations than low fat/high carbohydrate (LF/HC) meals. Blood samples were collected every 30-60 minutes for 24 h from 19 women (BMI = 24.2 ± 0.7 kg/m2; %body fat = 31 ± 1) on 2 randomized days during which the subjects consumed 3 isocaloric 730 kcal meals containing either 60/20% or 20/60% of energy as fat/carbohydrate. Meal-induced insulin secretion and overall insulin and glycemic responses (24 h area under the curve; AUC) were larger on the LF/HC than the HF/LC day (p< 0.0001). During LF/HC feeding, there were increase of leptin 4-6 hours after breakfast (+38 ± 7%; p< 0.001) and lunch (+78 ± 14%; p< 0.001) over morning trough levels. The changes of plasma leptin at these times were significantly greater than after HF/LC meals (p< 0.0025). During LF/HC feeding, plasma leptin increased from a morning baseline of 10.7 ± 1.6 ng/ml to a nocturnal (0030-0230 h) maximum of 21.3 ± 1.3 ng/ml (Δ = +10.6 ± 1.3 ng/ml; %Δ = +123 ± 16%; p< 0.0001). The amplitude of the nocturnal rise of leptin and the 24 h leptin AUC were 21 ± 8% (p< 0.005) and 36 ± 11% (p< 0.0025) larger, respectively, on the LF/HC than the HF/LC day. In summary, meal-associated, nocturnal, and 24 h circulating leptin concentrations are lower after HF/LC meals than after LF/HC meals. The reduction of leptin secretion may be a consequence of reduced insulin stimulation of adipocyte glucose metabolism. Decreased circulating leptin concentrations could contribute to tne effects of HF/LC diets to promote weight gain and obesity.
|Original language||English (US)|
|Journal||Investigative Ophthalmology and Visual Science|
|State||Published - Feb 15 1996|
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