Reducing the dietary omega-6: Omega-3 utilizing α-linolenic acid; Not a sufficient therapy for attenuating high-fat-diet-induced obesity development nor related detrimental metabolic and adipose tissue inflammatory outcomes

Abstract

Aims: To examine the effect of manipulating the omega-6:omega-3 (1:1, 5:1, 10:1, and 20:1) utilizing only α-linolenic and linoleic acid within a clinically-relevant high-fat diet (HFD) composed of up to seven sources of fat and designed to be similar to the standard American diet (MUFA:PUFA of 2:1, 12% and 40% of calories from saturated and total fat, respectively) on body composition, macrophage polarization, inflammation, and metabolic dysfunction in mice. Methods: Diets were administered for 20 weeks. Body composition and metabolism (HOMA index and lipid profile) were examined monthly. GC-MS was utilized to determine the eicosapentaenoic acid (EPA):arachidonic acid (AA) and the docosahexaenoic acid (DHA):AA in AT phospholipids. Adipose tissue (AT) mRNA expression of chemokines (MCP-1, Fetuin-A, CXCL14), marker genes for M1 and M2 macrophages (CD11c and CD206, respectively) and inflammatory markers (TNF-α, IL-6, IL-1β, TLR-2, TLR-4, IL-10, GPR120) were measured along with activation of NFκB, JNK, and STAT-3. Macrophage infiltration into AT was examined using F4/80 immunohistochemistry. Results: Any therapeutic benefit produced by reducing the omega-6:omega-3 was evident only when comparing the 1:1 to 20:1 HFD; the 1:1 HFD resulted in a lower TC:HDL-C and decreased AT CXCL14 gene expression and AT macrophage infiltration, which was linked to a higher EPA:AA and DHA:AA in AT phospholipids. However, despite these effects, and independent of the omega-6:omega-3, all HFDs, in general, led to similar levels of adiposity, insulin resistance, and AT inflammation. Conclusion: Reducing the omega-6:omega-3 using α-linolenic acid is not an effective therapy for attenuating obesity and type II diabetes mellitus development. © 2014 Enos et al.