Cardiometabolic characteristics of people with metabolically healthy and unhealthy obesity [ThighMuscle]
Some people with obesity are resistant to the adverse metabolic effects of excess adiposity and are considered to have “metabolically healthy obesity” (MHO). However, the mechanisms responsible for MHO are not clear. We performed comprehensive cardiometabolic profiling in 20 adults with MHO (defined by features of normal insulin sensitivity), 20 age-, sex-, and BMI-matched adults with metabolically unhealthy obesity (MUO), and 15 adults who were metabolically healthy and lean (MHL). More than 120 variables were evaluated, including body composition, beta-cell function, 24-hour plasma metabolic profile, rates of de novo lipogenesis and cholesterol synthesis, plasma adipokine concentrations, oxidative stress, plasma lipoprotein profiles, cardiovascular structure/function, skeletal muscle bioactive lipids, and both adipose tissue and skeletal muscle transcriptomics. Using dimensionality reduction approaches, measures of insulinemia and skeletal muscle ceramides were the strongest discriminators of MHO and MUO status. These data clarify the characteristics associated with preserved metabolic health in response to obesity. Overall design: Comprehensive cardiometabolic profiling was conducted in 20 adults with metabolically healthy obesity (MHO, defined as normal fasting glucose, glucose tolerance, HbA1c, intrahepatic triglyceride, serum triglycerides, and whole-body insulin sensitivity), 20 age-, sex-, and BMI-matched adults with metabolically unhealthy obesity (MUO, defined as prediabetes and hepatic steatosis), and 15 adults who were metabolically healthy and lean (MHL). Vastus lateralis muscle biopsy samples were subjected to bulk RNA-sequencing.