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

  • Original Article
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Lipids

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.

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Abbreviations

ARA:

Arachidonic acid

ALA:

Alpha linolenic acid

CREB:

cAMP response element binding protein

COX:

Cyclooxygenase

CVD:

Cardiovascular disease

DGAT:

Acyl CoA:diacylglycerol acyltransferase

DHA:

Docosahexaenoic acid

DPA:

Docosapentaenoic acid

EPA:

Eicosapentaenoic acid

FFA:

Free fatty acids

FABP-4:

Fatty acid binding protein-4

GLC:

Gas liquid chromatography

HDL:

High density lipoprotein

IL-6:

Interleukin-6

LA:

Linoleic acid

LDL:

Low density lipoprotein

LDL-r:

Low density lipoprotein receptor

LPL:

Lipoprotein lipase

MUFA:

Monounsaturated fatty acid

n-3 PUFA:

Omega-3 polyunsaturated fatty acid

n-6 PUFA:

Omega-6 polyunsaturated fatty acid

NEFA:

Non-esterified fatty acids

PPARγ:

Peroxisome proliferator-activated receptor-gamma

PUFA:

Polyunsaturated fatty acid

SCD-1:

Stearoyl-CoA desaturase-1

SFA:

Saturated fatty acid

SREBP-1:

Sterol regulatory element binding protein

TC:

Total-cholesterol

TAG:

Triacylglycerols

TNF-α:

Tumor necrosis factor

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Acknowledgments

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.

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  1. Department of Biochemistry, Memorial University, St. John’s, NL, A1B 3X9, Canada

    Kayode A. Balogun & Sukhinder K. Cheema

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  1. Kayode A. Balogun
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Correspondence to Sukhinder K. Cheema.

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Balogun, K.A., Cheema, S.K. Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion. Lipids 51, 25–38 (2016). https://doi.org/10.1007/s11745-015-4105-x

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  • DOI: https://doi.org/10.1007/s11745-015-4105-x

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