Various factors acting during the perinatal period exert long-lasting effects on energy metabolism in adulthood, including the propensity to obesity. Adipocyte hormone leptin may represent a key signal of nutritional status and a potential programming factor. Transient postnatal increases in circulating leptin levels in rodents (known as leptin surge), with a maximum in about 2-week-old mice, may increase later susceptibility to diet-induced obesity. However, the long-term effects of leptin are controversial, and the primary source of leptin during the surge is unclear. Most of the published results are based on experiments using obesity-prone C57BL/6J (B6) mice. Here, we focused on the role of circulating leptin levels and several related variables, measured in 2- and 4-week-old, on the development of obesity in both (i) B6 mice and (ii) obesity-resistant A/J mice of both genders. Posttranscriptionally controlled leptin secretion from subcutaneous white adipose tissue, the largest fat depot in mice pups, was the primary determinant of plasma leptin levels. The obesogenic effect of a high-fat diet (HFD), administered between 12 - 24 weeks of age, was observed in B6 but not A/J mice. Only leptin levels at 2 weeks correlated with both body weight and adiposity of the 24-week-old HFD-fed mice, with a stronger effect on adiposity in A/J mice. In conclusion, our results demonstrate a positive correlation between leptin surge and adiposity in adulthood. They newly document that the imprinting of the adiposity trajectory by leptin is influenced by sex and diet but independent of total body fat. Our findings support the view that the major role of leptin is to ensure the non-toxic accumulation of energy reserves in body fat depots and suggest that this mechanism is programmed early in the postnatal period.
This research was supported by the project National Institute for Research of Metabolic and Cardiovascular Diseases (Programme EXCELES, ID Project No. LX22NPO5104) Fu nded by the European Union Next Generation EU