oa The Role of 4-hydroxynonenal in Human Preadipocyte Proliferation and Differentiation

Accumulation of lipid peroxidation products in response to oxidative stress can cause dysfunction and pathology in a variety of tissues. In this study, we investigated the presence of 4-hydroxynonenal (4-HNE), the most abundant lipid peroxidation end product, in paired subcutaneous (SC) and omental (OM) tissues obtained from morbidly obese individuals undergoing weight reduction surgery. We further assessed 4-HNE effect on proliferation and differentiation of preadipocytes derived from these tissues in two metabolically distinct groups. Levels of 4-HNE accumulation were positively correlated between the paired SC and OM tissues (R² = 0.9, p = 0.01) and exhibited a higher accumulation in OM-adipocytes and connective tissues compared to SC-derived counterparts. Exposure of tissues-derived preadipocytes to physiological levels of 4-HNE caused inhibition of proliferation and differentiation of SC, but not OM-derived preadipocytes. When samples were dichotomized into insulin sensitive (IS) and insulin resistant (IR) groups based on their HOMA-IR index, 4-HNE treatment caused a greater reduction of both proliferation by 76% with a mean difference of 11.4% (3–45.3) and differentiation capacity by 56% with a mean difference of 25.9% (3.9–55.7) in IS compared to IR. This data suggest that 4-HNE induced oxidative stress plays a role in the regulation of adipocyte proliferation and differentiation in a depot and insulin sensitivity-specific manners and may therefore contribute to metabolic dysfunction associated with insulin resistance. This research was sponsored by Qatar National Research Fund (QNRF), Grant number NPRP6-235-1-048.