(−)-Secoisolariciresinol attenuates high-fat diet-induced obesity in C57BL/6 mice

Abstract

Flaxseed lignan, secoisolariciresinol has been reported to possess health benefits. We previously synthesized each stereoisomer of secoisolariciresinol and found that (−)-secoisolariciresinol reduces lipid accumulation and induces adiponectin production in 3T3-L1 adipocytes. Here we show the effects of (−)-secoisolariciresinol on high-fat diet-induced obesity in C57BL/6 male mice. Oral administration of (−)-secoisolariciresinol for 28 consecutive days significantly suppressed the gain of body weight. Increased serum adiponectin level and decreased gene expression of fatty acid synthase and sterol regulatory element-binding protein-1c in liver, which are related to fatty acid synthesis, were observed in the mice orally administered with (−)-secoisolariciresinol. In addition, subcutaneous injection of (−)-secoisolariciresinol also significantly suppressed the gain of body weight. Serum leptin levels were significantly increased by treating with (−)-secoisolariciresinol or (−)-enterolactone. Subcutaneous injection of (−)-secoisolariciresinol, (−)-enterolactone, or (−)-enterodiol promoted gene expression of acyl-CoA oxidase, carnitine palmitoyl transferase-1, and peroxisome proliferator-activated receptor α, which are related to β-oxidation. Overall results suggest that (−)-secoisolariciresinol exerts a suppressive effect on the gain of body weight of mice fed a high-fat diet by inducing gene expression of adiponectin, resulting in the altered expression of various genes related to the synthesis and β-oxidation of fatty acids.