Poster Topical Area: Energy and Macronutrient Metabolism
Location: Hall D
Poster Board Number: 526
Objective. The objective of this study was to determine the effect of inhibition of Fads2, the rate limiting enzyme in polyunsaturated fatty acid (PUFA) metabolism, in combination with increased dietary n-3 PUFAs on metabolic and immune parameters, when given to high fat fed mice.
Methods. 7 week old C57BL/6 male mice (n=20) were placed on a 45% high fat diet (HF-n6, n-6:n-3 PUFA ratio 13:1) for 6 weeks. Half of the animals (n=10) were then switched to a 45% high fat diet containing high amounts of n-3 fatty acids (HF-n3, n-6:n-3 PUFA ratio 1:3), predominantly in the form of (eicosapentaenoic acid) EPA and (docosahexaenoic acid) DHA. Concurrently, a subgroup receiving either diet (n=5) was given daily oral doses of a Fads2 inhibitor at a dose of 100mg/kg/day for 2 weeks. This inhibitor will reduce synthesis of all Fads2 products including arachidonic acid (AA), EPA and DHA. Food consumption and mouse weight were monitored throughout the experiment. Fasting glucose, glucose tolerance and body composition were determined pre and post intervention. Mice were euthanized by CO2 inhalation and organs harvested for characterization. Splenocytes were isolated and stimulated with either lipopolysaccharide or concanavalin A to determine in vitro proliferation capacity.
Results.Consistent with the diet-induce obesity model, mice fed the HF-n6 diet gained significantly more weight compared to the chow diet group (p<0.01), but inhbition of Fads2, with or without the HF-n3 diet, reduced weight gain (p<0.01). The loss of weight was a result of fat loss (p<0.01) as there was no change in lean mass. Interestingly, animals fed the HF-n3 diet in the absence of the Fads2 inhibitor had a slight increase in lean mass (p=0.06). This was consistent with an increase in the size of the gastrocnemius in mice fed the HF-n3 diet (p=0.06). While no difference in glucose tolerance was observed, fasting glucose tended to be lower in the presence of the Fads2 inhibitor, irrespective of diet. To determine the effect of inhibition of Fads2, on immunity, splenic B and T cell proliferation indices were determined. No difference were observed in any of the proliferation indices measured.
Conclusion. Inhibition of Fads2, with or without increased n-3 PUFAs can alter body composition but does not affect the proliferation capacity of splenic lymphocytes.
Marie van der Merwe
University of Memphis