Phytother Res. , 2020., Jul;34(7):1578-1586. doi: 10.1002/ptr.6634. PMID: 32050052

Genes with a known role in obesity include peroxisome proliferator-activated receptor alpha (PPAR-α) and leptin. PPAR-α is a transcription factor that is involved in energy metabolism. Increased expression of PPAR-α has been observed to prevent diet-induced obesity (DIO). Reduced methylation at the promoter region of PPAR-α and antioxidant supplementation increased PPAR-α expression in rats. Leptin acts on the central nervous system to regulate energy intake and expenditure. The current study was conducted to determine effects of health promoting compounds of flaxseed, n-3 FA and SDG, on DNMTs, PPAR-α, and leptin expression; and also to identify the relationships among DNMTs, PPAR-α, and leptin genes and subsequently, body weight in an obese animal model. Both the HF + DF and high-fat+flaxseed oil (HF + FO) groups gained significantly less weight than the HF +WF group which may indicate the ability of each component of flaxseed, the SDG and n-3 FA, to protect against weight gain separately rather than in combination. Additionally, the HF + FO group consumed significantly less food than the HF + WF and low-fat control (LFC) groups which raises the possibility that a high-fat diet accompanied by flaxseed oil intake may be protective against weight gain through regulation of food intake. This provides evidence that supplementation of defatted flaxseed, as a source of SDG, may have prevented weight gain by a mechanism other than through regulating intake, such as epigenetic regulation. In the adipose tissue, the expression of DNMT1 was reduced in all diet groups, and DNMT3a expression was reduced in the LFC and HF + FO groups compared to the HFC group. Down-regulated DNMTs expression might be attributed to n-3 FA and SDG compounds in flaxseed. The possibility exists that SDG present in flaxseed are not capable of interacting with DNMT catalytic site, and thus not capable of epigenetic modification by DNA methylation. This same effect may be responsible in the current study, but more research is needed to determine the relationship between flaxseed consumption and DNMT expression.

Jalili C Pezeshki M Askarpour M et al.