Thermoneutrality Inhibits Thermogenic Markers and Exacerbates Nonalcoholic Fatty Liver in Mice (P21-068-19)

Abstract

ObjectivesNonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, affecting more than a third of the US population and 25% of the global population. In this study, we investigated whether manipulation of brown adipose tissue (BAT) activity via housing C57BL/6 J mice under two different housing temperatures (22°C vs 27°C) influences the development of NAFLD. MethodsMale C57BL/6 J mice were randomly allocated to 4 groups (8 mice/group). Briefly, mice housed at the standard temperature (ST) (22°C) or thermoneutral temperature (TT) (27°C) were fed either a control chow diet (CHD) (Picolab rodent diet 20, LabDiet) with a regular drinking water or an “fast food” diet (FFD) (Research Diets, D12079B) plus fructose 23.1 g/L and glucose 18.9 g/L added to the drinking water for 10 weeks. ResultsMice under TT had significant less food intake compared to their counter partners under ST, regardless of diets. Mice exposed to TT and fed FFD had the highest body weight and plasma leptin level among all groups. For mice fed CHD, mice at TT did not present hepatic steatosis although they slightly gained more body weight compared to mice at ST. For mice fed FFD, thermoneutral housing mice had greater liver weight, liver triglyceride, and exacerbated hepatic steatosis compared to the standard housing mice. Moreover, for mice fed FFD, TT compared to ST had significantly elevated expression of fatty acid synthase, sterol regulatory element-binding transcription factor 1, fatty acid translocase, and monocyte chemoattractant protein-1 in liver. By contrast, TT did not change expression of above genes in mice fed CHD. Furthermore, thermoneutrally housed mice displayed a decrease in gene expression of thermogenic markers, such as uncoupling protein 1, elongation of very long chain fatty acids 3, and cell death-inducing DNA fragmentation factor alpha-like effector A in BAT and inguinal white adipose tissue (WAT). ConclusionsThermoneutrality inhibits expression of thermogenic markers in both BAT and WAT, which correlated to exacerbated NAFLD in mice. Our data indicate that activating BAT and/or promoting WAT browning may represent a potential strategy for the management of NAFLD. Funding SourcesThe College of Human Sciences of Texas Tech University; the National Center for Complementary & Integrative Health.