Impaired immune function and enhanced hepatic injury on CCl4‐treated mice fed a Western Diet.

The purpose of the present study was to elucidate the influence of feeding a western diet (WD) on hepatic injury and inflammation. Accordingly, male C57BL/6 mice were fed a purified AIN 93G control diet (CD) that contained (% calories) butter fat (12% calories), sucrose (29.8%), protein (15.3%), and cholesterol (0.3% w/w). To simulate a western diet (WD), CD was enriched in butter fat (41%) and cholesterol 1.5% (w/w). After 3 wk of feeding carbon tetrachloride (CCl 4 ) was administered (2ul/g in olive oil; i.p.) to induce necroinflammation. Liver injury in CD‐fed mice, indexed by elevated serum ALT activity and pericentral necrosis 24h after CCl 4 exposure, was markedly diminished by 72h. In contrast, WD exacerbated hepatocellular necrosis 72h post exposure. Immunohistochemical staining revealed that necrotic areas in mice fed CD were associated with infiltrating neutrophils and enhanced ICAM‐1 expression. TNF‐α expression was analyzed by real‐time PCR and was also increased. Feeding WD attenuated CCl 4 ‐induced neutrophil accumulation, ICAM‐1 content, and TNF‐α mRNA expression. Consistent with blunted inflammation, feeding WD enhanced circulating adiponectin levels (13.7 ± 0.7 ng/ml) compared to diet matched controls (10.9 ± 0.4 ng/ml) and CD‐fed mice 24h after CCl 4 (10.5 ± 0.7 ng/ml). To index healing, hepatic expression of TGF‐β and collagen α1 were evaluated 72h after CCl 4 ; expression of both markers was 4‐fold higher in the CD group compared to the WD group. Collectively, these results demonstrate that consuming WD blunted hepatic inflammation and healing, which was likely the result of altered cytokine expression (e.g. adiponectin and TGF‐β). The impaired immune function may have potentiated the late phase (72h) of injury. NIH grant: 3 P01 DK043785‐14S1