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Diet‐induced activation of PPARδ improves liver metabolic profiles in mice
Author(s) -
Paton Chad M,
Vaughan Roger A,
Alpergin Erbu,
AssadiPorter Fariba,
Dowd Michael K
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.684.2
Subject(s) - medicine , endocrinology , peroxisome proliferator activated receptor , beta oxidation , peroxisome , lipogenesis , fatty acid , fatty liver , chemistry , lipid metabolism , metabolism , biology , biochemistry , receptor , disease
Peroxisome proliferator activator receptor delta (PPARδ) has been shown to be an effective target to combat obesity and metabolic disease, however non‐pharmacological methods of activation have yet to be identified. We tested the ability of various naturally occurring oils to increase PPARδ activity and found that cottonseed oil (CSO) was effective in activating liver expression and activity. Male C57BL/6 mice were fed a diet supplemented with various oils (50% Kcal from fat‐matched for macronutrient and caloric content) for 4 weeks with body weight and food intake measured weekly. Total energy expenditure, glucose tolerance, and tissue protein and mRNA expression was measured after 4‐weeks. NMR‐based metabolomics was conducted on liver homogenates to examine changes in pathways of macronutrient metabolism. There were no differences between chow‐ and CSO‐fed mice in body weight or food intake (Kcal/wk) however total energy expenditure and fat oxidation increased compared to chow‐fed groups. Additionally, CSO‐fed mice displayed significantly elevated liver PPARδ and Pgc‐1 expression that correlated with energy expenditure. Metabolomic analyses revealed that the livers of CSO‐fed mice closely matched those of chow‐fed and significantly differed from other fat‐enriched diet groups using principal component analyses. Fatty acid composition of the diets and livers revealed no significant differences in lipid species between groups, with the exception of dihydrosterculic acid (DHSA). DHSA is a cyclopropene fatty acid that may be responsible for increasing fatty acid oxidation in liver. Additional studies designed to assess the effect of DHSA on PPARδ‐mediated metabolic control are ongoing. Taken together, our observations support the hypothesis that CSO may be useful as a dietary means to increase PPARδ expression with concomitant elevations in total energy expenditure and improved hepatic fatty acid oxidation. A diet containing 50% of total calories from CSO did not cause weight gain and promoted improved molecular adaptations in both liver and skeletal muscle. Support or Funding Information Cotton Incorporated.