Endogenous Omega-3 Polyunsaturated Fatty Acids Preserved Morphology and Function of Brown Fat Impaired by High-Fat Diet Feeding in Mice

Abstract

ObjectivesThe role of omega-3 polyunsaturated fatty acids (PUFA) in regulation of energy homeostasis remains poorly understood. In this study, we aimed to investigate how omega-3 PUFA regulate the morphology and function of brown fat tissue (BAT) in mice. MethodsSixteen-week-old male wild type (WT) and transgenic fat-1 mice, which are capable of synthesizing omega-3 PUFA, were fed a low-fat diet (LFD) or a high-fat diet (HFD) for 13 weeks. Metabolic tissues, including BAT, white adipose tissues, and liver, were collected for biochemical and histological analysis. ResultsTransgenic fat-1 mice had significantly lower body weight and total fat mass compared with WT mic fed HFD. In addition, fat-1 mice had improved glucose tolerance compared with WT. We found that in WT mice, HFD induced larger lipid droplet accumulation (“whitening”) in BAT, whereas “whitening” in BAT was significantly alleviated in fat-1 mice. Real time PCR showed that some thermogenic markers, such as uncoupling protein 1 (UCP1), carnitine palmitoyltransferase I (CPT I), and cell death activator (CIDE-A), were expressed more in fat-1 mice compared with WT mice fed HFD. Moreover, fat-1 mice had significantly lower lipopolysaccharide levels compared with WT mice. Real time PCR showed that fat-1 mice had significantly lower levels of inflammatory markers, including monocyte chemoattractant protein-1 (MCP1), tumor necrosis factor (TNFα), and mouse macrophage marker (F4/80) in BAT. In a separate experiment, we found that fat-1 mice resisted UCP suppression by LPS injection. ConclusionsThis study demonstrated that HFD led to obesity and “whitening” of BAT in WT mice; conversely, omega-3 PUFA in fat-1 mice preserved morphology and function of BAT impaired by HFD. We revealed that the dysfunction of BAT may be attributed to increased LPS production due to HFD feeding, and that omega-3 PUFA alleviate the dysfunction of BAT through inhibition of LPS production. Funding SourcesThis study was supported by the Fortune Education Foundation (New York, USA) and Sansun Life Sciences (Hong Kong, China).