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 ω-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 ω-3 PUFA. Here we studied the AT of high fat (HF)-fed fat-1 transgenic mice that convert endogenous ω-6 to ω-3 PUFA while maintaining equivalent fat accretion as their wild-type (WT) counterparts.


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 8weeks from 6weeks 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 PPARγ transcriptional activity.


CONCLUSIONS
These data provide unprecedented evidence that ω-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 ω-3 PUFA on adipogenesis. Furthermore we provide primary evidence suggesting that protectins likely contribute to these effects via their influence on PPARγ.
Department of Medicine, Québec Heart and Lung Institute, Université Laval, Ste-Foy, Québec, Canada and Laval University Hospital Research Center, Metabolism, Vascular and Renal Health Axis, Ste-Foy, Québec, Canada.
Phillip J
PJ
White
Department of Medicine, Québec Heart and Lung Institute, Université Laval, Ste-Foy, Québec, Canada and Laval University Hospital Research Center, Metabolism, Vascular and Renal Health Axis, Ste-Foy, Québec, Canada.
Patricia L
PL
Mitchell
Department of Medicine, Québec Heart and Lung Institute, Université Laval, Ste-Foy, Québec, Canada and Laval University Hospital Research Center, Metabolism, Vascular and Renal Health Axis, Ste-Foy, Québec, Canada.
Michael
M
Schwab
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre and the Faculty of Pharmacy, Laval University, Québec, Canada.
Jocelyn
J
Trottier
Laboratory for Lipid Medicine and Technology, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Jing X
JX
Kang
Laboratory of Molecular Pharmacology, CHU-Québec Research Centre and the Faculty of Pharmacy, Laval University, Québec, Canada.
Olivier
O
Barbier
Department of Medicine, Québec Heart and Lung Institute, Université Laval, Ste-Foy, Québec, Canada and Laval University Hospital Research Center, Metabolism, Vascular and Renal Health Axis, Ste-Foy, Québec, Canada. Electronic address: Andre.Marette@crchul.ulaval.ca.
André
A
Marette
D017667:Adipocytes / Q000648:ultrastructure; D000273:Adipose Tissue / Q000033:anatomy & histology* / Q000378:metabolism*; D000818:Animals; D018957:CD59 Antigens / Q000235:genetics* / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D048429:Cell Size; D004734:Energy Metabolism / Q000235:genetics; D004822:Epididymis / Q000166:cytology / Q000187:drug effects; D044943:Fatty Acid Desaturases / Q000235:genetics / Q000378:metabolism; D015525:Fatty Acids, Omega-3 / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D047495:PPAR gamma / Q000235:genetics; D020218:Response Elements / Q000235:genetics
D018957:CD59 Antigens; D029742:Caenorhabditis elegans Proteins; D015525:Fatty Acids, Omega-3; D047495:PPAR gamma; C466741:fat-1 protein, C elegans; D044943:Fatty Acid Desaturases
Adipose; Microarray; Obesity; Omega-3 PUFA; Protectins