Leptin expression and secretion are strongly correlated with body fat mass in animals and humans in cross-sectional studies, and experimental alterations in body fat content are associated with parallel changes in leptin expression and secretion [1,2]. Leptin expression and secretion in animals is also acutely influenced by food restriction and refeeding [2,3]. In obese humans and animals undergoing energy restriction, amelioration of many of the metabolic abnormalities associated with obesity is apparent before any major effect on body fat content. In an investigation of the mechanisms responsible for these early effects we have studied metabolic responses after 4 and 28 days of energy restriction in a group of moderately obese human subjects with and without non-insulindependent diabetes mellitus (NIDDM). We report here the responses of circulating leptin concentrations under these conditions, and their relationships to changes in macronutrient intakes and body composition. Subjects and methodsSubjects: Nine (5 female, 4 male) obese subjects (BMI = 31.6 ± 0.8 (mean ± SEM) kg/m 2 ) with normal glucose tolerance and no family history of NIDDM, and 9 (4 female, 5 male) obese subjects (BMI = 32.3 ± 0.9) with mild NIDDM (fasting plasma glucose Summary The response of serum leptin to short (4 days) and prolonged (28 days) energy restriction (50 % reduction in energy intake) was determined in 18 (9 male, 9 female) moderately obese humans (body mass index 32.0 ± 0.6 kg/m 2 mean ± SEM), 9 of whom had mild non-insulin-dependent diabetes mellitus (NIDDM). Body composition was assessed before and at the end of the energy restriction using DEXA. The subjects lost a measured 2.6 ± 0.4 kg of body fat after 28 days and an estimated 0.3 kg at 4 days. Serum leptin fell to 64 ± 3 % of baseline levels at day 4 and further to 46 ± 4 % at day 28. In a multiple correlation analysis, the change in leptin concentration at day 4 was significantly related to the change in dietary carbohydrate intake (partial r = 0.68, p < 0.005) but not to changes in fat (r = 0.12) or protein (r = 0.02) intakes. There was a 1 : 1 relationship between the changes in leptin and dietary carbohydrate (regression slope = 1.0 ± 0.3). Gender, or the presence of NIDDM had no effects on these responses. This pronounced fall in serum leptin in association with reduced carbohydrate intake before substantial loss of body fat suggests a role for leptin in defending the body's carbohydrate stores and implicates leptin in the satiating effects of carbohydrate. Dietary or other interventions which maintain leptin levels during weight reduction may lead to improvements in weight loss. [Diabetologia (1997) 40: 348-351]

Even in obese subjects with an average lipid profile, modest weight loss reduces atherogenicity, independently of type 2 diabetes, and abdominal fat loss is specifically related to such improvements.

No abstract