Flaxseed lignans alleviate high fat diet-induced hepatic steatosis and insulin resistance in mice: Potential involvement of AMP-activated protein kinase

• Lignans content varied widely among 12 flaxseed cultivars grown in China.
• Flaxseed lignan SDG improved lipid metabolism and glucose homeostasis in mice.
• SDG alleviated hepatic steatosis and insulin resistance in high fat diet-fed mice.
• SDG protected against hepatic steatosis and insulin resistance by enhancing insulin signalling.
• AMPK activation may be one of mechanisms by which SDG exert metabolic benefits.

Hepatic steatosis and insulin resistance are highly prevalent and play a vital role in the development of nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). The present study examined the protective effects of naturally occurring flaxseed lignan secoisolariciresinol diglucoside (SDG) on these metabolic disorders resulting from high fat diet (HFD). SDG (0.05%, w/w) supplementation for 16 weeks attenuated body weight gain, hyperlipidaemia and hepatic steatosis in HFD (60% kcal from fat)-challenged C57BL/6J mice. Moreover, SDG lowered fasting serum glucose and insulin, and improved homeostasis model assessment of insulin resistance (HOMA-IR) index, glucose tolerance, and insulin response in HFD-fed mice. Furthermore, SDG prevented HFD-induced inhibition of protein kinase B, insulin receptor substrate-1 and AMP-activated protein kinase activation in the liver of HFD-fed mice. These findings indicate that SDG supplementation alleviates hepatic steatosis and insulin resistance, at least in part, by enhancing insulin signalling and AMPK activation.