oa Insulin Resistance-associated Impairment Of Preadipocyte Differentiation In Human Abdominal Obesity

OBJECTIVE: Differentiation capacity of human preadipocytes exhibits depot specific variation and is influenced by local cytokine production. The effect of obesity-induced insulin resistance on preadipocyte differentiation and its relation to proinflammatory cytokine release was investigated. RESEARCH DESIGN AND METHODS: Differentiation of preadipocytes obtained from subcutaneous & omental tissue biopsies isolated from obese patients undergoing weight reduction surgery and their cytokines release were compared between insulin sensitive and insulin resistant subjects. RESULTS: Compared to subcutaneous-derived cells, omental cells expanded from the same patients showed diminished differentiation, marked by increased proinflammatory cytokines secretion. When subjects were dichotomized into insulin sensitive & insulin resistant depending on their HOMA-IR, preadipocytes derived from insulin sensitive subjects exhibited a greater ability to differentiate into larger adipocytes with more lipid droplets, marked by a lower expression and secretion of IL-6 and TNFα. Addition of these cytokines inhibited preadipocyte differentiation in insulin sensitive-derived cultures, suggesting that proinflammatory cytokines may underlie inhibition of differentiation seen in insulin resistant patients-derived cultures. CONCLUSIONS: These findings suggest that insulin-resistance is associated with impaired preadipocyte differentiation and increased proinflammatory cytokines release. Understanding mechanisms underlying impaired preadipocyte differentiation associated with insulin resistance may help future treatment strategies.