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.


Article metrics loading...

Loading full text...

Full text loading...

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error