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Introduction: Non-alcoholic fatty liver disease (NAFLD) can progress to more severe stages, such as steatohepatitis and fibrosis. Thermoneutral housing together with high-fat diet promoted NAFLD progression in C57BL/6J mice. Due to possible differences in steatohepatitis development between different C57BL/6 substrains, we examined how thermoneutrality affects NAFLD progression in C57BL/6N mice. Methods: Male mice were fed standard or high-fat diet for 24 weeks and housed under standard (22°C) or thermoneutral (30°C) conditions. Results: High-fat feeding promoted weight gain and hepatic steatosis, but the effect of thermoneutral environment was not evident. Liver expression of inflammatory markers was increased, with a modest and inconsistent effect of thermoneutral housing; however, histological scores of inflammation and fibrosis were generally low (<1.0), regardless of ambient temperature. In standard diet-fed mice, thermoneutrality increased weight gain, adiposity, and hepatic steatosis, accompanied by elevated de novo lipogenesis and changes in liver metabolome characterized by complex decreases in phospholipids and metabolites involved in urea cycle and oxidative stress defense. Conclusion: Thermoneutrality appears to promote NAFLD-associated phenotypes depending on the C57BL/6 substrain and/or the amount of dietary fat. [ABSTRACT FROM AUTHOR]

Prevalence of non‐alcoholic fatty liver disease (NAFLD) increases in line with obesity and type 2 diabetes, and there is no approved drug therapy. Polyunsaturated fatty acids of n‐3 series (omega‐3) are known for their hypolipidaemic and anti‐inflammatory effects. Existing clinical trials suggest varying effectiveness of triacylglycerol‐ or ethyl ester‐bound omega‐3 in the treatment of NAFLD, without affecting advanced stages such as non‐alcoholic steatohepatitis. Preclinical studies suggest that the lipid class used to supplement omega‐3 may determine the extent and nature of their effects on metabolism. Phospholipids of marine origin represent an alternative source of omega‐3. The aim of this review is to summarise the available evidence on the use of omega‐3 phospholipids, primarily in obesity‐related NAFLD, and to outline perspectives of their use in the prevention/treatment of NAFLD. A PubMed literature search was conducted in May 2021. In total, 1088 articles were identified, but based on selection criteria, 38 original papers were included in the review. Selected articles describing the potential mechanisms of action of omega‐3 phospholipids have also been included. Preclinical evidence clearly indicates that omega‐3 phospholipids have strong antisteatotic effects in the liver, which are stronger compared to omega‐3 administered as triacylglycerols. Multiple mechanisms are likely involved in the overall antisteatotic effects, involving not only the liver but also adipose tissue and the gut. Robust preclinical evidence for strong antisteatotic effects of omega‐3 phospholipids in the liver should be confirmed in clinical trials. Further research is needed on the possible effects of omega‐3 phospholipids on advanced NAFLD. [ABSTRACT FROM AUTHOR]