, Volume 51, Issue 1, pp 25–38 | Cite as

Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion

  • Kayode A. Balogun
  • Sukhinder K. CheemaEmail author
Original Article


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.


Adipocyte hypertrophy DGAT-2 FABP-4 Leptin N-3 PUFA Obesity 



Arachidonic acid


Alpha linolenic acid


cAMP response element binding protein




Cardiovascular disease


Acyl CoA:diacylglycerol acyltransferase


Docosahexaenoic acid


Docosapentaenoic acid


Eicosapentaenoic acid


Free fatty acids


Fatty acid binding protein-4


Gas liquid chromatography


High density lipoprotein




Linoleic acid


Low density lipoprotein


Low density lipoprotein receptor


Lipoprotein lipase


Monounsaturated fatty acid

n-3 PUFA

Omega-3 polyunsaturated fatty acid

n-6 PUFA

Omega-6 polyunsaturated fatty acid


Non-esterified fatty acids


Peroxisome proliferator-activated receptor-gamma


Polyunsaturated fatty acid


Stearoyl-CoA desaturase-1


Saturated fatty acid


Sterol regulatory element binding protein






Tumor necrosis factor



This research was supported by funds from the Natural Sciences and Engineering Research Council (NSERC) and Canada Foundation for Innovation (CFI). We acknowledge the technical support provided by Sophie Gagnon for her help with GC. We would also like to acknowledge Dr. Sherri Christian for her assistance with measuring the adipocyte size. The authors declare no conflict of interest.

Compliance with Ethical Standards

Conflict of interest

The authors report no conflict of interest.


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© AOCS 2015

Authors and Affiliations

  1. 1.Department of BiochemistryMemorial UniversitySt. John’sCanada

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