Metabolically unhealthy adipose tissue is characterized by reductions in mitochondrial size and function

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.

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.

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.

We conclude that targeting mitochondrial fusion processes would be a rational strategy to improve metabolic health, independent of total fat mass.