Myostatin and adipokines: The role of the metabolically unhealthy obese phenotype in muscle function and aerobic capacity in young adults

Obesity is often associated with metabolic disorders. However, some obese people can present a metabolically healthy phenotype, despite having excessive body fat. Obesity-related cytokines, such as myostatin (MSTN), leptin (LP) and adiponectin (ADP) appear to be key factors for the regulation of muscle and energy metabolism. Our aim was to compare lipid, glucose-insulin and inflammatory (tumor necrosis factor alpha; TNF-α) profiles, muscle function, energy expenditure and aerobic capacity between healthy normal-weight (NW) adults, metabolically healthy obese (MHO) and metabolically unhealthy obese (MUHO) adults; to study the associations between these outcomes and the cytokines MSTN, ADP, LP; and to establish cutoffs for MSTN and LP/ADP to identify the MUHO phenotype. Sixty-one young adults (NW, n = 24; MHO, n = 16; MUHO, n = 21) underwent body composition (body fat -BF and muscle mass - MM), energy expenditure at rest (RER) and aerobic capacity (VO2peak) evaluation, muscle strength and endurance tests and blood profile characterization (glucose-insulin homeostasis and serum MSTN, ADP, LP and TNF-α). MHO and MUHO had a BMI ≥ 30 kg m−2. MUHO was defined as presenting ≥3 criteria for metabolic syndrome (NCEP/ATPIII) in association with insulin resistance (HOMA-IR ≥3.46). MSTN and LP/ADP were associated with MM, MetS and glucose-insulin profile; MSTN was associated with TNF-α and only LP/ADP was associated with parameters of obesity and VO2peak. Neither MSTN nor LP/ADP was associated with muscle functions (p < .05 for adjusted correlations). Both of them were able to discriminate the MUHO phenotype: MSTN [AUC(95%CI) = 0.71(0.55-0.86), MSTN > 517.3 pg/mL] and LP/ADP [AUC(95%CI) = 0.89(0.81-0.97), LP/ADP > 2.14 pg/ng]. In conclusion, high MSTN and LP/ADP are associated with MetS, glucose-insulin homeostasis impairment and low muscle mass. Myostatin is associated with TNF-α and leptin-to-adiponectin ratio is associated with body fatness and aerobic capacity. Neither MSTN nor LP/ADP is associated with energy expenditure, muscle strength and endurance. Myostatin and adipokines cutoffs can identify the metabolically unhealthy obese phenotype in young adults with acceptable accuracy.