Fish Oil Enriched in EPA, but Not in DHA, Reverses the Metabolic Syndrome and Adipocyte Dysfunction Induced by a High-Fat Diet

Abstract

This study aimed to investigate the effects of two commercially available fish oils (FOs) containing different proportions of two omega-3 fatty acids (FA), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), on the metabolic and endocrine dysfunctions of white adipose tissue resulting from obesity. Male C57BL/6J mice, 8 weeks old, received a control or high-fat diet (CO and HF groups, with 9% and 59% energy from fat, respectively) for 8 weeks. The next 8 weeks, the HF group was subdivided into HF, HF+FO/E (HF+5:1 EPA:DHA), and HF+FO/D (HF+5:1 DHA:EPA). Supplementation was performed by gavage, three times a week. All groups that received the HF diet had lower food and caloric intake, but a higher fat intake, body weight (BW) gain, glucose intolerance, and a significant increase in inguinal (ING), retroperitoneal (RP), and epididymal (EPI) adipose tissues when compared to the CO group. Additionally, HF and HF+FO/D groups showed insulin resistance, adipocyte hypertrophy, increased lipolysis and secretion of TNF-α, resistin and IL-10 adipokines by ING and RP adipocytes, and adiponectin only by the HF+FO/D group in ING adipocytes. All of these effects were completely reversed in the HF+FO/E group, which also showed partial reversion in BW gain and glucose intolerance. Both the HF+FO/E and HF+FO/D groups showed a reduction in ING and RP adipose depots when compared to the HF group, but only HF+FO/E in the EPI depot. HF+FO/E, but not HF+FO/D, was able to prevent the changes triggered by obesity in TNF-α, Il-10, and resistin secretion in ING and RP depots. These results strongly suggest that different EPA:DHA ratios have different impacts on the adipose tissue metabolism, FO being rich in EPA, but not in DHA, and effective in reversing the changes induced by obesity.

Fish Oil Supplementation Mitigates High-Fat Diet-Induced Obesity: Exploring Epigenetic Modulation and Genes Associated with Adipose Tissue Dysfunction in Mice

“…Compared to the CO diet, mice fed with HFD showed an approximately 50% increase in fasting blood glucose (Figure 1C) and glucose intolerance (Figure 1D), with an expressive (82 %) increase in the area under the curve (Figure 1E). Thus, our diet-induced obesity model was characterized, confirming our previous results [10,11,16]. We subsequently supplemented the animals with FO (HFD+FO group) in the last 8 weeks of the 16-week experimental protocol with HFD.…”

“…As expected [10,11], mice consuming HFD presented a significant increase of 50 % in body mass when compared to the CO group, and the HFD+FO group was still 40 % higher in relation to CO group, but presented a significant reduction of ~30% (P < 0.05) compared to the HFD group (Figure 2A). Moreover, animals in the HFD group exhibited a significant increase in the mass of the visceral epididymal (Epi) fat depot (by ~3x), while treatment with FO completely prevented this increase in fat mass (Figure 2B).…”

“…Additionally, these animals showed improvements in adipocyte function, including reductions in hypertrophy and metabolic and endocrine dysfunctions associated with obesity. Moreover, FO supplementation effectively downregulated the expression of pro-inflammatory cytokines, suggesting its potential in mitigating obesity-related endocrine disorders [9][10][11][12]. Notably, fish oil (FO) treatment appears to modulate the inflammation pathway, suggesting its significance in the epigenetic regulation of WAT cells and providing new insights into obesity management.…”

Different ratios of DHA/EPA reverses insulin resistance by improving adipocyte dysfunction and lipid disorders in HFD-induced IR mice

“…9 Many studies suggest that fish oil enriched in EPA, but not in DHA, reverses the metabolic syndrome and adipocyte dysfunction induced by HFD. 10 However, our previous study found that different doses of DHA and EPA supplemented alone had different effects on the regulation of insulin sensitivity in IR mice, of which DHA was more effective. It is worth noting that natural DHA and EPA in fish oil products are usually present in mixtures.…”

“…12 A recent study showed that dietary supplementation with EPA-rich fish oil (DHA/EPA ratio of 1 : 5) reversed HFDinduced obesity and impaired glucose tolerance in mice, while DHA-rich fish oil (DHA/EPA ratio of 5 : 1) did not. 10 Moreover, phospholipids (DHA/EPA ratio of 3 : 1) from herring roe improve plasma glucose tolerance in healthy, young adults, 13 and Mycobacterium tuberculosis lecithin rich in EPA and DHA may be developed as an effective food supplement for IR inhibition. 14 However, some research suggests that it has little or no effect on postprandial changes in plasma lipids, glucose, and insulin concentrations under different fatty acid compo-sitions.…”