Adipocyte-specific gp130 signalling mediates exercise-induced weight reduction

Background Repetitive physical activity is a well-established intervention to reduce obesity and to prevent weight regain. Besides increased energy expenditure, reduced caloric intake may contribute to exercise-induced weight loss in obesity. Using adipocyte-specific glycoprotein 130 knockout (gp130(Delta adipo)) mice, we recently unravelled that obesity-induced interleukin-6 (IL-6) signalling in adipose tissue contributes to circulating levels of the two anorectic hormones leptin and insulin. Herein, we aimed to investigate the role of adipocyte-specific IL-6 signalling in exercise-mediated appetite control and, hence, weight reduction in obesity. Methods gp130(Delta adipo) and control littermate mice (gp130(F/F)) were repetitively exercised during a 12-week period of HFD-feeding. Thermogenesis was determined using thermography and food intake as well as energy expenditure were assessed in metabolic cages. Circulating IL-6, insulin and leptin levels were measured using immunoassays. Protein levels of phosphorylated STAT3, JAK2 and Akt were determined in the hypothalamus by Western blot technique. Results Repetitive physical activity reduced food intake and HFD-induced weight gain in gp130(F/F) but not gp130(Delta adipo) mice. In contrast, energy expenditure was not different between the genotypes. Circulating insulin and leptin levels were significantly reduced in gp130(Delta adipo) mice. Moreover, hypothalamic leptin and insulin signalling were enhanced in exercised gp130(F/F) but not gp130(Delta adipo) mice as demonstrated by elevated pSTAT3, pJAK2 and pAkt protein levels. Conclusion Adipocyte-specific IL-6 signalling is involved in exercise-mediated regulation of food intake and weight reduction in HFD-fed mice.