Abstract
BackgroundLow hepatic content of n-3 PUFA has been associated with NAFLD in humans. Whether this is associated with reduced dietary intake or increased turnover of these FA is not clear. We have here investigated the effects of dietary fat quality on hepatic lipid storage and transcriptomics over time.AimTo investigate the effects of quality of fat in a high fat diet (HFD) over time on hepatic lipid storage and liver transcriptomics.Methods and ResultsMale C57BL/6J mice were fed control, HFD-eicosapentaenoic acid (EPA)/ docosahexaenoic acid (DHA) or HFD-corn oil diet for 8 or 12 weeks. Body weight, body composition, plasma and hepatic triglyceride contents were measured. Hepatic transcriptomes were analysed by microarray followed by gene-set enrichment analyses. At 8 weeks, the HFD-corn oil mice had higher body weight and adipose depot mass than the HFD-EPA/DHA but there were no differences at 12 weeks. Hepatic triglyceride content was lower in HFD-EPA/DHA fed compared with the HFD-corn oil fed mice at both time-points. Enrichment analyses of the hepatic transcriptomes showed that lipid/fatty acid biosynthesis; transport and homeostasis were lower in the HFD-EPA/DHA fed compared with the HFD-corn oil fed mice. Genes encoding proteins associated to cytoplasmic lipid droplets were expressed at higher levels in livers from the HFD-corn oil compared to HFD-EPA/DHA mice.ConclusionsDietary EPA and DHA counteracted development of HFD-induced fatty liver. The liver transcriptome data implicate that the quality of dietary fat could modulate Ppar-related gene expression that in turn affects hepatic lipid storage and maintenance of metabolic health.Electronic supplementary materialThe online version of this article (doi:10.1186/s12944-015-0072-8) contains supplementary material, which is available to authorized users.
Highlights
It is becoming more established that an increased lipid content in the liver can be viewed as a driver of the metabolic dysfunctions that are observed in obesity [1]
At 8 weeks, the High fat diet (HFD)-corn oil mice had higher body weight and adipose depot mass than the HFD-eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) but there were no differences at 12 weeks
Hepatic triglyceride content was lower in HFD-EPA/DHA fed compared with the HFD-corn oil fed mice at both time-points
Summary
It is becoming more established that an increased lipid content in the liver can be viewed as a driver of the metabolic dysfunctions that are observed in obesity [1]. A recent retrospective study showed that subjects diagnosed with NAFLD or non-alcoholic steatohepatitis (NASH) had reduced life expectancy due. It has been suggested that a high dietary intake of sucrose/fructose, cholesterol and saturated fat can be associated with NAFLD in humans [5, 6]. Whether reduced dietary intake of n-3 fatty acids is related to NAFLD progression, and whether low hepatic n-3 levels are cause or consequence of NASH is not clear. Low hepatic content of n-3 PUFA has been associated with NAFLD in humans. Whether this is associated with reduced dietary intake or increased turnover of these FA is not clear. We have here investigated the effects of dietary fat quality on hepatic lipid storage and transcriptomics over time
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