α-Linolenic acid increases the G0/G1 switch gene 2 mRNA expression in peripheral blood mononuclear cells from obese patients: a pilot study

Abstract

BackgroundRecent evidence has demonstrated that the G0/G1 switch gene 2 (G0S2) is an important negative regulator of the rate-limiting lipolytic enzyme adipose triglyceride lipase-mediated lipolysis. It has been revealed that α-linolenic acid (ALA), a plant-based essential omega-3 polyunsaturated fatty acids, reduces adipose tissue lipolysis. However, it is not known whether G0S2 is implicated in ALA-induced inhibition of lipolysis. The purpose of this pilot study is to investigate the effect of ALA on G0S2 gene expression in peripheral blood mononuclear cells (PBMC) of obese patients and the potential influence of G0S2 gene expression in ALA-induced inhibition of lipolysis.MethodsA total of 26 obese patients were randomly assigned to be treated with or without ALA treatment (~4.0 g daily) for 12 weeks: the ALA-treated group (n = 14) or the untreated control group (n = 12). Plasma triglyceride (TG), free fatty acids (FFA), glycerol, interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), as well as the mRNA expression levels of proliferator-activated receptor gamma (PPAR-γ), G0S2, and G protein-coupled receptor 120 (GPR120) in PBMC were repeatedly examined from fasting obese patients before and after ALA treatment.ResultsALA significantly decreased plasma TG, FFA, glycerol, IL-6, and TNF-α levels and increased the mRNA expression levels of PPAR-γ, G0S2, and GPR120 in PBMC, compared with the untreated control group. In obese patients from the ALA-treated group, decreased plasma FFA (a biomarker for lipolysis) level was significantly correlated with increased PPAR-γ (a functional omega-3 fatty acids receptor) and G0S2 (a direct target gene of PPAR-γ) mRNA expression in PBMC, while decreased plasma FFA level was not correlated with increased GPR120 (another functional omega-3 fatty acids receptor) mRNA expression in PBMC.ConclusionThis study shows that ALA increases G0S2 gene expression in PBMC in parallel with the decrease of plasma FFA level in obese patients. Increased G0S2 gene expression might contribute to the beneficial anti-lipolytic effect of ALA in obese patients.

The Immunometabolic Roles of Various Fatty Acids in Macrophages and Lymphocytes

“…One aspect of the anti-inflammatory actions of omega-3 FAs could be attenuation of macrophage differentiation towards more inflammatory phenotypes. The treatment of obese people with α-linolenic acid (4 g/daily for 12 weeks) decreased plasma free FAs and pro-inflammatory cytokines and increased PPARγ mRNA expression in mononuclear cells [57]. Adolescents with obesity who received 1.2 g/day of omega-3 FAs for the same period of intervention had elevated serum omega-3 FA concentrations together with lower inflammatory markers [58].…”

Metabolomic and gene expression analysis to study the effects of dietary saturated and polyunsaturated fats

“…The mRNA levels of LDLR, IL8, and TGF were not changed during the intervention. The increased expression level of PPARG has also been observed after 12-week supplementation with 4g/day of ALA (17). To our knowledge, no whole genome profiling data exist from human dietary intervention study with ALA.…”

Dietary Fatty Acids at the Crossroad between Obesity and Colorectal Cancer: Fine Regulators of Adipose Tissue Homeostasis and Immune Response

“…Other dietary intervention studies based on vegetable oils, such as flaxseed oil and camelina sativa oil, which are enriched in ALA, have demonstrated anti-inflammatory effects on PBMC gene expression. In particular, a significant increase in PPAR-γ levels has been reported in individuals with impaired fasting glucose and in obese and T2DM subjects [ 68 , 92 , 93 ]. Furthermore, the expression of several genes involved in lipid metabolism and inflammation was favourably changed in PBMC when replacing SFA-rich with ω6 PUFA-rich diets [ 80 ].…”