Haptoglobin deficiency determines changes in adipocyte size and adipogenesis

Haptoglobin (Hp) is an inflammatory and adiposity marker, its expression during obesity being specifically induced in the white adipose tissue (WAT). We previously reported that when challenged with a high fat diet (HFD) Hp(-/-) mice are partially protected from the onset of insulin resistance and hepatosteatosis. The aim of the present study was to get further insights into Hp function in WAT. To this end, we performed histological and gene expression analysis of the Hp(-/-) WAT, both in standard and obesity conditions, and investigated how Hp deficiency impacts adipogenesis and WAT development. The average size and percentage of very large adipocytes were respectively smaller and reduced in HFD Hp(-/-) mice as compared with HFD WT. The expression of perilipin, HSL and angiogenesis related markers were increased in HFD Hp(-/-) mice. Lean adult Hp(-/-) showed significantly larger adipocytes and lower subcutaneous WAT expression of aP2 and LPL with respect to WT. Hp(-/-) young mice (P30) were characterized by larger adipocyte size and lower expression of adipocyte and adipogenesis markers. Comparison of adipocyte size distribution between young and adult mice revealed attenuated changes in Hp(-/-) mice compared with WT. Mouse embryonic fibroblasts from Hp(-/-) mice were less capable of accumulating triglycerides and exhibited lower expression of PPAR gamma, aP2, FAS, LPL and Leptin. In conclusion, Hp deficiency tends to blunt the effect of age and diet on the size of adipocytes, which show less susceptibility to develop hypertrophy during obesity and a reduced adipogenic/ hyperplastic potential during youth. In addition, Hp deficiency impacts negatively on adipogenesis.