title: Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion.
abstract: Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)-3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n-3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi-purified diets (20 % w/w fat) containing high n-3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n-3 PUFA (10 % w/w), medium n-3 PUFA (4 % w/w), or low n-3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase-2 (DGAT-2), fatty acid binding protein-4 (FABP-4) and leptin were measured. The high n-3 PUFA group showed higher levels of total n-3 PUFA in gonadal TAG compared to the medium and low n-3 PUFA groups (P < 0.001). The high n-3 PUFA male group had a lower adipocyte area compared to the medium and low n-3 PUFA group (P < 0.001); however, no difference was observed in females. The high n-3 PUFA male group showed lower mRNA expression of FABP-4, DGAT-2 and leptin compared to the low n-3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n-3 PUFA group compared to the other groups. Our findings show for the first time that n-3 PUFA prevents adipocyte hypertrophy by downregulating FABP-4, DGAT-2 and leptin; the effects are however sex-specific.
authors.affiliation: Department of Biochemistry, Memorial University, St. John's, NL, A1B 3X9, Canada.
authors.forename: Kayode A
authors.initials: KA
authors.lastname: Balogun
authors.affiliation: Department of Biochemistry, Memorial University, St. John's, NL, A1B 3X9, Canada. skaur@mun.ca.
authors.forename: Sukhinder K
authors.initials: SK
authors.lastname: Cheema
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D000818:Animals; D051048:Diacylglycerol O-Acyltransferase / Q000378:metabolism*; D019587:Dietary Supplements; D015536:Down-Regulation / Q000187:drug effects*; D050556:Fatty Acid-Binding Proteins / Q000378:metabolism*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D006984:Hypertrophy / Q000517:prevention & control; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012727:Sex Characteristics
chemical_list: C493411:Fabp4 protein, mouse; D050556:Fatty Acid-Binding Proteins; D015525:Fatty Acids, Omega-3; C516957:DGAT2 protein, mouse; D051048:Diacylglycerol O-Acyltransferase
keywords: Adipocyte hypertrophy; DGAT-2; FABP-4; Leptin; N-3 PUFA; Obesity