Transgenic ω-3 PUFA enrichment alters morphology and gene expression profile in adipose tissue of obese mice: Potential role for protectins

Objective. Dietary administration of omega-3 polyunsaturated fatty acids (PUFA) is often associated with altered adipose tissue (AT) morphology and/or function in obese mice. Yet, it is unclear whether this is an indirect consequence of reduced weight gain or results from direct actions of omega-3 PUFA. Here we studied the AT of high fat (HF)-fed fat-1 transgenic mice that convert endogenous omega-6 to omega-3 PUFA while maintaining equivalent fat accretion as their wild-type (WT) counterparts. Materials and methods. Adipocyte size profiling, Affymetrix microarray pathway analysis, qPCR and protectin identification and analysis were performed in epididymal AT from hemizygous fat-1(+/-) mice and their wild type littermates that had been fed a HF diet for 8 weeks from 6 Weeks of age. Results. Despite equivalent fat pad mass, we found that epididymal AT from HF-fed transgenic animals possesses fewer large and very large but more mid-size adipocytes compared to WT mice. In order to better understand the underlying mechanisms contributing to the observed alteration in adipocyte size we performed an Affymetrix microarray. Pathway analysis of these data highlighted adipogenesis, cholesterol biosynthesis, insulin signaling, prostaglandin synthesis/regulation and small ligand GPCRs as points where differentially expressed genes were significantly overrepresented. Observed changes were confirmed for four candidate genes: Cnr1, Cnr2, Faah and Pparg by qPCR. Finally we demonstrated that protectin DX is present in AT and that protectin DX and protectin D1 promote comparable PPAR gamma transcriptional activity. Conclusions. These data provide unprecedented evidence that omega-3 PUFA coordinately regulate AT gene expression programs in a manner that is independent of restriction of weight gain or fat accrual and highlight an important influence of omega-3 PUFA on adipogenesis. Furthermore we provide primary evidence suggesting that protectins likely contribute to these effects via their influence on PPAR gamma. (C) 2015 Published by Elsevier Inc.