Adipocyte Mitochondrial Function Is Reduced in Human Obesity Independent of Fat Cell Size

Abstract

CONTEXT: It has been suggested that mitochondrial dysfunction in adipocytes contributes to obesity-related metabolic complications. However, obesity results in adipocyte hypertrophy, and large and small adipocytes from the same depot have different characteristics, raising the possibility that obesity-related mitochondrial defects are an inherent function of large adipocytes. OBJECTIVE: Our goal was to examine whether obesity, independent of fat cell size and fat depot, is associated with mitochondria dysfunction. DESIGN: We compared adipocyte mitochondrial function using a cross-sectional comparison study design. SETTING: The studies were performed at Mayo Clinic, an academic medical center. PATIENTS OR OTHER PARTICIPANTS: Omental and/or abdominal subcutaneous adipose samples were collected from 20 age-matched obese and nonobese nondiabetic men and women undergoing either elective abdominal surgery or research needle biopsy. INTERVENTION: Interventions were not conducted as part of these studies. MAIN OUTCOME MEASURES: We measured mitochondrial DNA abundance, oxygen consumption rates, and citrate synthase activity from populations of large and small adipocytes (separated with differential floatation). RESULTS: For both omental and subcutaneous adipocytes, at the cell and organelle level, oxygen consumption rates and citrate synthase activity were significantly reduced in cells from obese compared with nonobese volunteers, even when matched for cell size by comparing large adipocytes from nonobese and small adipocytes from obese. Adipocyte mitochondrial content was not significantly different between obese and nonobese volunteers. Mitochondrial function and content parameters were not different between small and large cells, omental, and subcutaneous adipocytes from the same person. CONCLUSION: Adipocyte mitochondrial oxidative capacity is reduced in obese compared with nonobese adults and this difference is not due to cell size differences. Adipocyte mitochondrial dysfunction in obesity is therefore related to overall adiposity rather than adipocyte hypertrophy.