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.

Breastmilk with a high omega‐6 to omega‐3 fatty acid ratio induced cellular events similar to insulin resistance and obesity in 3T3‐L1 adipocytes

“…RNA concentration and purity were measured using NanoDrop 2000 (Thermo Scientific, USA), and cDNA was prepared as per our previous publication . Primers for diacylglycerol acyltransferase‐2 (DGAT2), stearoyl‐CoA desaturase (SCD)‐1, RPLPO (large ribosomal protein) and leptin for quantitative polymerase chain reaction were designed using NCBI primer blast (http://www.ncbi.nlm.nih.gov/ tools/primer‐blast/) as per our previous publication and obtained from IDT technologies (IA, USA). Amplification was performed using iQ SYBER Green Supermix (Biorad, USA).…”

Black Raspberry Seed Oil Improves Lipid Metabolism by Inhibiting Lipogenesis and Promoting Fatty‐Acid Oxidation in High‐Fat Diet‐Induced Obese Mice and db/db Mice

“…The final body weight of the db/50% was significantly ( p < 0.05) lower than that of the db/ST, although there were no significant ( p > 0.05) differences in the food intake among the db/ST, db/50%, and db/100% groups (Lee et al, ). The number of laboratory animals used for this experiment was selected based on previous studies (Balogum & Cheema, ; Bargut et al, ; Devarshi et al, ; Fink et al, ; Xu et al, ). All the animal procedures were approved by the Institutional Animal Care and Use Committee of Seoul National University (approval no: SNU‐120630‐4 and SNU‐130617‐2) as reported in the previous articles (Lee et al, , ).…”

“…The quantity and quality of dietary fat play an important role in the development of obesity (Balogum & Cheema, 2016). Diet with a higher ratio of n-6 to n-3 polyunsaturated fatty acids (PUFA) may increase type 2 diabetes and obesity (Devarshi, Jangale, Ghule, Bodhankar, & Harsulkar, 2013).…”

“…The impact of dietary n-3 PUFA on lipid metabolism has been the subject of several studies, most of which have mainly focused on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) (Balogum & Cheema, 2016;Bargut, Frantz, Mandarim-de-Lacerda, & Aguila, 2014;Batetta et al, 2009;Han et al, 2015;Hashimoto et al, 2013;Jump, 2008). Studies on ALA, another n-3 PUFA, have been scarcely carried out and mostly dealt with perilla oil or flaxseed oil (Devarshi et al, 2013;Kaithwas & Majumdar, 2012).…”

Transcriptome Analysis of Potential miRNA Involved in Adipogenic Differentiation of C2C12 Myoblasts

“…By contrast, the CEBPA‐deficient cell, in a sense, can modulate adipocyte differentiation (Liu et al, ; Wang et al, ). Previous studies have indicated that the fatty acid binding protein‐4 (FABP4) has the ability to regulate glucose and lipid metabolism (Balogun & Cheema, ; Xu et al, ). The concerted action of these adipogenic TF ultimately drives the expression of adipocyte‐specific factors, for instance, enzymes that are responsible for the synthesis and storage of triglycerides in lipid droplets (Gregoire, Smas, & Sul, ).…”