Potential of Aerobic Physical Training to Minimize the Effects of Leptin Deficiency in Female Mice

Abstract

Aerobic physical training (APT) is an important strategy for prevention and treatment of comorbidities such as type 2 diabetes and obesity. Leptin and adiponectin play an important role in energy metabolism, whose imbalance is strongly related to obesity and insulin resistance (IR). Although women have higher levels of leptin and adiponectin compared to men, in conditions such as obesity and/or type 2 diabetes these levels decrease, abolishing the protective effects of these adipokines in females. This study investigated the effects of APT on the metabolic parameters in leptin‐deficient female mice. For this, 8‐week‐old wild C57BL/J6 (C57) or leptin‐deficient ob/ob (Lepob) female mice were separated into the groups sedentary (S) (C57S, n = 6 and LepobS, n = 5) and trained (T) (LepobT, n = 8). The APT was performed during 1 h/day at 60% of maximal speed achieved in the maximal physical exertion test, 5 times/week for eight weeks. The procedures were approved by the Ethics Committee of the School of Arts, Sciences and Humanities of University of Sao Paulo (#001/2017). LepobS and LepobT groups increased body weight, the weight of retroperitoneal (WAT‐RP) and subcutaneous (WAT‐SC) fat pads compared to C57S. Adipocyte area and diameter of WAT‐RP and WAT‐SC were higher in both LepobS and LepobT compared to C57S, however the APT decreased the WAT‐SC adipocyte area and diameter in LepobT group compared to LepobS. LepobS and LepobT groups showed lower weight of pancreas, gastrocnemius and plantar muscles compared to C57S, however APT prevented the mass reduction of gastrocnemius and plantar muscles in LepobT. Food intake was higher in LepobS compared to C57S, which was counteracted by APT in the LepobT group. The LepobS had fasting hyperglycemia (131 ± 1.02 mg/dL) and glucose intolerance (AUC: 31522 ± 1148 mg/dL/120min) compared to C57S (92 ± 2.51 mg/dL and AUC: 20339 ± 1857 mg/dL/120min). Despite of LepobT group had shown glucose intolerance (AUC: 30085 ± 547 mg/dL/120min), the APT decreased the fasting glycemia (114 ± 6.11 mg/dL) compared to LepobS group. Adiponectin level did not change among groups, as well as the relative area of islets in the pancreatic tissue. During the maximal physical exertion test, LepobT showed higher maximal speed, time to exhaustion and speed on the VO2máx compared to LepobS group. In conclusion, APT prevented the loss of gastrocnemius and plantar muscles mass, reduced WAT‐SC adipocyte hypertrophy and food intake, improved fasting glycemia and aerobic capacity in leptin deficient female mice. Support or Funding Information FAPESP (#2018/22361‐9), CAPES, CNPq