Conclusions
We conclude that targeting mitochondrial fusion processes would be a rational strategy to improve metabolic health, independent of total fat mass.
Methods
Obesity statuses ranged from very lean to severely obese (<9%->50%, n = 44), which were equivalent in healthy or unhealthy NHPs (metabolic syndrome score difference, p < 0.001). We evaluated SQ AT histology, electron microscopy, tissue proteins, and bioenergetics.
Objective
Adipose function, not mass, underpins metabolic health. Lean and obese nonhuman primates (NHPs) naturally develop metabolic syndrome. Mitochondria-related measures in subcutaneous adipose tissue (SQ AT) and peripheral blood mononuclear cells may elucidate differences that transcend adiposity measures.
Results
Unhealthy adipocytes had mitochondria one-half the size of healthy adipocytes (p < 0.01), whereas adipocyte cell sizes were comparable. Consistent with small mitochondria, we saw deficiencies in mitochondrial fusion and quality-control proteins in SQ AT from unhealthy NHPs (all p < 0.05). Smaller mitochondria in unhealthy adipocytes were consistent with low SQ AT tissue respiration (p < 0.05). Mitochondrial size was specifically reduced with unhealthiness, as mitochondrial abundance, size, and related metrics were unrelated to adiposity. Isolated stromal vascular cells showed comparable respirometry profiles, substantiating specificity of adipocyte-related mitochondrial defects. Peripheral blood mononuclear cell bioenergetic indices were increased in unhealthy NHPs, indicative of immune cell activation, and correlated to SQ AT inflammatory cytokines. Conclusions: We conclude that targeting mitochondrial fusion processes would be a rational strategy to improve metabolic health, independent of total fat mass.