Adenovirus type 36 reduces fatty acid oxidation by increasing Cidec/FSP27

Abstract

It is well documented that adenovirus type 36 infection (Ad‐36) results in obesity. However, the molecular mechanism of Ad‐36 cause obesity remains unknown. Recent studies suggest that Cell death‐inducing DNA fragmentation factor‐alpha‐like effectors (CIDE) family proteins play important roles in modulating energy homeostasis, aging and the development of metabolic diseases such as obesity and diabetes. Cidec/FSP27 is one of Cide family identified as a novel lipid droplet‐associated protein in adipocytes.We sought to investigate the effect of Ad‐36 infection on fatty acid oxidation, Cidec/FSP27, PGC 1a, LPL, UCP3 and ACC protein abundance in primary cultured human skeletal muscle cells. Muscle cells were infected with various doses (1.9 ‐ 7.6 PFU/cells) of Ad‐36 and adenovirus type 2 (Ad‐2) with non‐lipogenesis as negative control as well as uninfected control.Our data show that Ad‐36 significantly reduces fatty acid oxidation with does dependant manner (100±7%, 62±9%, 56±11%, and 43±5% in control, 1.9, 3.8, 7.6 doses of Ad‐36, P<0.01 and P<0.001 respectively), but Ad‐2 had little effect on fatty acid oxidation (P>0.05). Ad‐36 at dose of 3.8 PFU/cell substantially increased Cidec/FSP27, ACC abundance, slightly decreased LPL and increased PCG 1a proteins comparison with control (3.37±0.4, 2.02±0.21, 0.74±0.04 and 1.82 ±0.47 fold respectively). Ad‐2 only slightly increased these proteins (1.27±0.13, 1.28 ±0.24, 1.07±0.07 and 1.26±0.14 fold of control, p>0.05 respectively).This study suggests that Ad‐36 promotes Cidec/FSP27 and ACC protein expression, and decreases LPL abundance. Ad‐36 reduces fatty acid oxidation and increases lipid accumulation in the muscle cells may be mediated by elevated Cidec/FSP27 protein.