Abstract

Dietary habit is highly related to nonalcoholic fatty liver disease (NAFLD). Low-fat–high-carbohydrate (LFHC) diets could induce lean NAFLD in Asians. Previously, we found that a lard and soybean oil mixture reduced fat accumulation with a medium-fat diet; therefore, in this study, we evaluated the effect of a lard and soybean oil mixture (LFHC diet) on NAFLD and its underlying mechanisms. Mice in groups were fed with lard, soybean oil, or a lard and soybean oil mixture—an LFHC diet—separately. Our results showed that mixed oil significantly inhibited serum triglyceride, liver triglyceride, serum free fatty acids (FFAs), and liver FFAs compared with soybean oil or lard, and we found fewer inflammatory cells in mice fed with mixed oil. RNA-seq results indicate that mixed oil reduced FFAs transportation into the liver via decreasing liver fatty acid-binding protein 2 expression, inhibited oxidative phosphorylation via tumor necrosis factor receptor superfamily member 6 downregulation, and alleviated inflammation via downregulating inflammatory cytokine. The liquid chromatography–mass spectrometry results showed that the mixed oil promoted bile acid conjugated with taurine and glycine, thus activating G-protein-coupled bile acid receptor 1 for improved lipids metabolism. In conclusion, the lard and soybean oil mixture alleviated NAFLD.

Highlights

  • Nonalcoholic fatty liver disease (NAFLD) results from at least 5% of hepatocytes having steatosis, but not caused by known damage, such as alcohol, viruses, or drugs [1]

  • NAFLD is considered as a range of liver abnormalities from nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH), it has a variable course, and it can lead to cirrhosis and liver cancer

  • It was observed that the body fat rate of mice fed with the lard and soybean oil mixture was lower than those of mice fed with lard (~21%) and soybean oil (~16.7%) separately—illustrating that the lard and soybean oil mixture is beneficial in improved TG metabolism

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Summary

Introduction

Nonalcoholic fatty liver disease (NAFLD) results from at least 5% of hepatocytes having steatosis, but not caused by known damage, such as alcohol, viruses, or drugs [1]. NAFLD is the leading cause of chronic liver disease in the United States, affecting between 80 million and 100 million people, of which nearly 25% of cases progress to NASH [4]. An LFHC diet is considered superior to methionine- and choline-deficient diets for NASH models The reason for this is that patients with NASH are not choline deficient; methionine- and choline-deficient diets would only induce a histological appearance similar to NASH—with fat, inflammation, and fibrosis. These underlying defects are not related to human disease pathogenesis [2]

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