Abstract
Excess energy intake can trigger an uncontrolled inflammatory response, leading to systemic low-grade inflammation and metabolic disturbances that are hypothesised to contribute to cardiovascular disease and type 2 diabetes. The long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are suggested to mitigate this inflammatory response, but the mechanisms are unclear, especially at the tissue level. Adipose tissues, the first tissues to give an inflammatory response, may be an important target site of action for EPA and DHA. To evaluate the effects of EPA and DHA in white and brown adipose tissues, we fed male C57Bl/6J mice either a high fat diet (HFD) with 5% corn oil, an HFD with 40% of the corn oil substituted for purified EPA and DHA triglycerides (HFD-ED), or normal chow, for 8 weeks. Fatty acid profiling and transcriptomics were used to study how EPA and DHA affect retroperitoneal white and brown adipose tissues. HFD-ED fed mice showed reduced lipid accumulation and levels of the pro-inflammatory fatty acid arachidonic acid in both white and brown adipose tissues, compared with HFD-corn oil fed animals. The transcriptomic analysis showed changes in β-oxidation pathways, supporting the decreased lipid accumulation in the HFD-ED fed mice. Therefore, our data suggests that EPA and DHA supplementation of a high fat diet may be anti-inflammatory, as well as reduce lipid accumulation in adipose tissues.
Highlights
Obesity is characterized by excessive fat accumulation accompanied by weight gain, and often induces chronic low-grade inflammation, which in turn is a risk factor for type 2 diabetes (T2D), cardiovascular diseases (CVD), and other metabolic abnormalities [1]
The differing high fat diet (HFD) differed only in their composition of fatty acids (FA) (Table 2), based on the replacement of 40 % of the corn oil with oil enriched with eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), representing 2 % of the total diet weight and 13 % of total fat in the feed
2.4 gene ontologies (GO)-Terms Gene-Set Enrichment Analyses of Biological Processes Affected by the HFD Diets in White- and Brown Adipose Tissues In white adipose tissue (WAT), HFD-ED up-regulated BPs related to mitochondria including electron transport chain, fatty acid β-oxidation, mitochondrial-translation, and organization, whereas, these processes were down-regulated by HFD-corn oil compared with control animals (Figure 6)
Summary
Obesity is characterized by excessive fat accumulation accompanied by weight gain, and often induces chronic low-grade inflammation, which in turn is a risk factor for type 2 diabetes (T2D), cardiovascular diseases (CVD), and other metabolic abnormalities [1]. An important aspect to the role of adipose tissue in obesity is that WAT can transiently turn to beige adipocytes [4], which can use surrounding lipids through mitochondrial thermogenesis via uncoupling protein. This process is affected by gender [5] and external cues including environmental temperature [6]. We have used EPA and DHA enriched oil, rather than fish oil, to reduce the confounding, which may come from the presence of many other compounds besides EPA and DHA in fish oil This makes it possible to attribute the effects to these LC n-3 PUFAs
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