Suppression of adipocyte differentiation and lipid accumulation by stearidonic acid (SDA) in 3T3-L1 cells

Abstract

BackgroundIncreased consumption of omega-3 (ω-3) fatty acids found in cold-water fish and fish oil has been reported to protect against obesity. A potential mechanism may be through reduction in adipocyte differentiation. Stearidonic acid (SDA), a plant-based ω-3 fatty acid, has been targeted as a potential surrogate for fish-based fatty acids; however, its role in adipocyte differentiation is unknown. This study was designed to evaluate the effects of SDA on adipocyte differentiation in 3T3-L1 cells.Methods3T3-L1 preadipocytes were differentiated in the presence of SDA or vehicle-control. Cell viability assay was conducted to determine potential toxicity of SDA. Lipid accumulation was measured by Oil Red O staining and triglyceride (TG) quantification in differentiated 3T3-L1 adipocytes. Adipocyte differentiation was evaluated by adipogenic transcription factors and lipid accumulation gene expression by quantitative real-time polymerase chain reaction (qRT-PCR). Fatty acid analysis was conducted by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS).Results3T3-L1 cells treated with SDA were viable at concentrations used for all studies. SDA treatment reduced lipid accumulation in 3T3-L1 adipocytes. This anti-adipogenic effect by SDA was a result of down-regulation of mRNA levels of the adipogenic transcription factors CCAAT/enhancer-binding proteins alpha and beta (C/EBPα, C/EBPβ), peroxisome proliferator-activated receptor gamma (PPARγ), and sterol-regulatory element binding protein-1c (SREBP-1c). SDA treatment resulted in decreased expression of the lipid accumulation genes adipocyte fatty-acid binding protein (AP2), fatty acid synthase (FAS), stearoyl-CoA desaturase (SCD-1), lipoprotein lipase (LPL), glucose transporter 4 (GLUT4) and phosphoenolpyruvate carboxykinase (PEPCK). The transcriptional activity of PPARγ was found to be decreased with SDA treatment. SDA treatment led to significant EPA enrichment in 3T3-L1 adipocytes compared to vehicle-control.ConclusionThese results demonstrated that SDA can suppress adipocyte differentiation and lipid accumulation in 3T3-L1 cells through down-regulation of adipogenic transcription factors and genes associated with lipid accumulation. This study suggests the use of SDA as a dietary treatment for obesity.Electronic supplementary materialThe online version of this article (10.1186/s12944-017-0574-7) contains supplementary material, which is available to authorized users.

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“…Accordingly, inhibition of PPAR‐γ and C/EBP‐α can affect the growth and differentiation of adipocytes . On the other hand, SREBP‐1 c plays an essential role in lipid synthesis and metabolism by regulating its target lipogenic genes, including FAS , VLDLR and Scd 1 . In this study, our results showed that BMH473 may inhibit the adipogenesis and reduce the lipid accumulation in 3T3‐L1 preadipocytes, by downregulating the protein expression levels of PPAR‐Ɣ, C/EBP‐α and SREBP‐1 c, as well as the mRNA expression levels of VLDL , FAS and Scd 1 (Figure ).…”

“…56,57 On the other hand, SREBP-1 c plays an essential role in lipid synthesis and metabolism by regulating its target lipogenic genes, including FAS, VLDLR and Scd 1. [58][59][60][61][62] In this study, our results showed that BMH473 BMH473 demonstrated a significant hypoglycaemic activity by activating phosphorylation of AMPK-ACC, and then attenuating hepatic steatosis and gluconeogenesis in obese T2DM rats. In conclusion, BMH473 has the potential to be developed as an anti-diabetic drug, and offers an obvious advantage over anti-hyperlipidaemic therapy.…”

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“…As the name itself implies, this particular liver pathology is not associated with alcohol intake and exhibited by hepatic steatosis (Lee, Nam, Seong, & Ryu, ) and adipogenesis (Ma et al, ). 3T3‐L1 adipocytes and a methionine and choline deficient (MCD) diet are a widespread cell culture model (Li et al, ) and dietary animal models of NAFLD (Lee et al, ), respectively. Choline and methionine are two essential nutrient components deficiency of which impede beta‐oxidation and synthesis of very low‐density lipoprotein (VLDL) particles (Ibrahim, Hirsova, Malhi, & Gores, ).…”

“…fermented black radish, fibrosis, inflammation, MCD diet, steatosis deficient (MCD) diet are a widespread cell culture model (Li et al, 2017) and dietary animal models of NAFLD , respectively. Choline and methionine are two essential nutrient components deficiency of which impede beta-oxidation and synthesis of very low-density lipoprotein (VLDL) particles (Ibrahim, Hirsova, Malhi, & Gores, 2016).…”