Background: Synthetic Glucocorticoids (GC) are widely used for their immunosuppressive capability, however chronic use is associated with adverse metabolic effects that are exacerbated when GC is combined with a high fat diet. Omega (n)-3 PUFA supplementation has been shown to rescue GC-induced hyperlipidemia, hyperinsulinemia and inflammation.
Objective: To evaluate the effect of n-3 PUFAs during chronic GC treatment to prevent metabolic dysfunction.
Methods: 3-week old C57BL/6 male mice were weaned onto a high fat diet that would result in obesity and metabolic dysfunction with long-term consumption. After 3 weeks, experimental mice were switched to a high fat diet rich in n-3 PUFAs. Concomitantly, half of each dietary group received GC (40 mg/m2/day) in the form of oral prednisolone. All animals remained on their respective diets/treatments for an additional 4 weeks. Weight gain, glucose homeostasis, fatty liver and inflammation were measured, and epididymal white adipose tissue (eWAT) transcriptome analysed.
Results: Switching to a diet high in n-3 PUFAs during a 4-week GC protocol did not cause in significant changes in weight gain or glucose homeostasis but resulted in significant decreased eWAT accumulation and macrophage infiltration independent from GC therapy. However, eWAT transcriptome analysis demonstrate GC upregulation of the acute phase proteins Orm1 and Orm2 are limited with an n-3 PUFA diet.
Conclusions: Chronic GC therapy in combination with a Western type high fat diet results in eWAT accumulation and inflammation. A diet rich in n-3 PUFAs protects against adiposity and early transcriptional alterations involved in metabolic derangement during GC therapy.
Citation: Hill JL, Wyman JM, Godwin SM, Beech LA, Buddington RK, et al. 2020. Dietary Omega-3 Fatty Acids Reduce Adiposity and Alter Glucocorticoid-Associated Transcripts in Epididymal White Adipose Tissue of C57BL/6 Male Mice Raised on a High Fat Diet. J Obes Chronic Dis 4(1): 13-22.