Agradecimentos: The authors would like to thank the team at the Laboratory of Metabolic Disorders for their support and helpful advice and Coordination for the Improvement of Higher Education Personnel – Brazil (CAPES) – Finance Code 001 and the São Paulo Research Foundation (FAPESP) (grant # 16/23484–1, # 18/01863–6, and #19/07615–7) and Obesity and Comorbidities Research Center (OCRC) of the São Paulo Research Foundation (FAPESP) Ver menos

Abstract: The consumption of saturated fatty acids (SFA), the main compound in coconut oil (CO), can promote insulin and leptin resistance and are associated with inflammation and obesity. We investigated the effects of CO supplementation on leptin signaling in healthy mice. Swiss male mice received oral supplementation for eight weeks with 300 µL of water for the control group (CV) or CO (100 or 300 µL). Sensitivity to leptin/insulin was evaluated after eight weeks of supplementation. The CO induced endoplasmic reticulum stress and leptin resistance in the hypothalamus, as demonstrated by reduced effect on the energy expenditure, hypothalamic pJAK2 and pSTAT3, and POMC expression. In the adipose tissue, lipogenesis was favored and STAT3 and JAK2 signaling was impaired after CO supplementation. Furthermore, the supplementation with CO reduced pAKT in the hypothalamus, liver and white adipose tissue. These results show that CO induces hypothalamic and peripheral resistance to leptin and insulin in healthy mice Ver menos