Flaxseed, due to its nutritional components, can be considered as a promising adjunct intervention for reducing the risk of weight-related metabolic abnormalities such as dyslipidemia, insulin resistance, cardiovascular risk factors and it is a good choice for weight loss. Hesperidin is an antioxidant flavonoid found in high concentrations in citrus. Together, flaxseed, because of the high content of omega-3 and fiber and its other components, and hesperidin, due to its potent antioxidant activity can be an effective combination in managing NAFLD. A randomized, controlled, open-label clinical trial to investigate the efficacy of flax-hes supplementation in patients with NAFLD was conducted. In the present study, amelioration of dyslipidemia in response to supplementation with hesperidin and/or flaxseed was achieved. No differences were seen in control group, while in the other three groups, plasma levels of TG, TC, and LDL-C decreased significantly during 12 weeks. HDL-C levels also increased significantly in the flaxseed group. CAP score, as an indicator of hepatic steatosis, reduced considerably in all intervention groups, while no significant differences were detected among four groups. These findings indicate the significant effects of lifestyle modification on hepatic steatosis, which diluted the effects of supplements on liver steatosis. Only flaxseed supplementation could ameliorate the hepatic fibrosis. In conclusion, the study confirmed that hesperidin and flaxseed supplementation, alone or in combination together, improved glucose and lipid metabolism, while reduced some inflammatory factors and CAP score in NAFLD patients. The synergistic effects of their combination were observed on plasma glucose concentration and HOMA-IR.

Key Points

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.