Mitigation of non-alcoholic fatty liver disease in high fat-fed mice by the combination of decaffeinated green tea extract and voluntary exercise

Abstract We have shown that combination treatment with decaffeinated green tea extract (GTE) and voluntary exercise (Ex) reduce obesity and insulin resistance in high fat (HF)-fed mice to a greater extent than either treatment alone. Here, we investigated the effects of GTE-, Ex-, or the combination on the development of obesity-related NAFLD. Male C57BL/6 J mice were treated for 16 weeks with HF diet (60% energy from fat), HF supplemented with 7.7 g GTE/kg, HF plus access to a voluntary running wheel, or the combination. We found that treatment of mice with the combination mitigated the development of HF-induced NAFLD to a greater extent than either treatment alone. Combination-treated mice had lower plasma alanine aminotransferase (92% lower) and hepatic lipid accumulation (80% lower) than HF-fed controls: the effect of the single treatments were less significant. Mitigation of NAFLD was associated with higher fecal lipid and nitrogen levels. Combination treated, but not singly treated mice, had higher hepatic expression of genes related to mitochondrial biogenesis (sirtuin 1 [59%]; peroxisome proliferator-activated receptor γ coactivator 1α [42%]; nuclear respiratory factor 1 [38%]; and transcription factor B1, mitochondrial [89%]) compared to the HF-fed controls. GTE-, Ex-, and the combination-treatment groups also had higher hepatic expression of genes related to cholesterol synthesis and uptake, but the combination was not better than the single treatments. Our results suggest the combination of GTE and Ex can effectively mitigate NAFLD. Future studies should determine if the combination is additive or synergistic compared to the single treatments.