The Effects of Physical Activity on Markers of Hepatic Inflammation During Weight-Loss

Non-alcoholic fatty liver disease (NAFLD) represents a continuum that begins with accumulation of lipid in hepatic cells progressing to hepatic steatosis with inflammation (steatohepatitis), fibrosis, and cirrhosis. Weight-loss using dietary modification and physical activity are common strategies used for the treatment of NAFLD; however, it remains to be determined the effects of physical activity on hepatic inflammation during weight-loss. The purpose of this study was to determine the therapeutic role of physical activity on plasma and hepatic inflammatory markers during weight-loss. Male C57BL/6 mice were fed either a low-fat (LFD; 10% kcal fat) or high-fat (HFD; 60% kcal fat) diet for 10-weeks. Following 10-weeks, the HFD group was randomly assigned to either a LFD (Diet) or LFD with physical activity (Diet+PA) to induce weight loss for 8-weeks. After 8-weeks, reductions in body mass were observed in both Diet and Diet+PA groups (see Table 1.). Interestingly, the Diet+PA group lost significantly (P\u3c0.05) more body mass than the Diet group. Despite significant (P\u3c0.05) reductions in body mass and HOMA-IR, plasma TNF-α remained elevated in the Diet and Diet+PA groups. Moreover, Diet+PA plasma TNF-α was significantly (P\u3c0.05) greater than the HFD obese controls. Elevated plasma TNF-α in the Diet+PA was matched by a greater hepatic expression of IL-1β and IL-6 mRNA when compared to all groups. Interestingly, the expression of TGF-β1 mRNA was significantly (P\u3c0.05) reduced in the Diet+PA when compared to all groups. The elevated plasma TNF-α and expression of IL-1β and IL-6 mRNA are likely due to physical activity. It remains unclear as to the pro-inflammatory effects of physical activity during weight-loss; however, this may be part of a protective adaption to regular exercise. Furthermore, the reduced hepatic TGF-β1 mRNA levels suggest a protective strategy against fibrogenesis in the spectrum of liver disease. Table 1. Whole body and hepatic metabolic characteristics following weight-loss. Variables LFD (n=12) HFD (n=12) Diet (n=12) Diet+PA (n=12) Body mass (g) 30.2 ± 1.1 48.8 ± 0.5* 30.3 ± 0.7† 26.1 ± 0.3*,†,‡ HOMA-IR 22.9 ± 1.2 187.3 ± 7.5* 19.4 ± 8.8† 25.3 ± 10.5† IL-6 (pg/mL) 6.4 ± 0.7 6.2 ± 1.0 5.9 ± 0.9 6.4 ± 0.9 TNF-α (pg/mL) 30.8 ± 6.7 60.6 ± 5.3* 74.0 ± 8.1* 82.5 ± 7.7*,† IL-1β mRNA 1.00 ± 0.51 0.97 ± 0.34 1.20 ± 0.59 2.83 ± 0.62*,†,‡ IL-6 mRNA 1.00 ± 0.45 1.53 ± 0.50 1.16 ± 0.72 2.36 ± 0.55*,†,‡ TNF-α mRNA 1.00 ± 0.09 0.89 ± 0.08 0.94 ± 0.14 0.83 ± 0.06 TGF-β1 mRNA 1.00 ± 0.06 1.02 ± 0.06 1.02 ± 0.10 0.84 ± 0.05† Note. Data are presented as mean ± SEM. *Significantly (P\u3c0.05) different than LFD; †significantly (P\u3c0.05) different than HFD; ‡significantly (P\u3c0.05) different than Diet