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

Key Findings:

(-)-SECO, a synthetically prepared pure stereo isomer of SECO (a flaxseed lignan), can reduce triglyceride accumulation and adiponectin production in 3T3-L1 adipocytes, suggesting a way to treat obesity by reducing fat accumulation. Here, sterically pure (-)-SECO suppressed fat accumulation in high-fat diet-induced obesity in C57BL/6 mice. Results were in a dose-dependent fashion and appeared to be due to regulating the expression of various genes related to fatty acid synthesis and beta-oxidation. Oral administration of (-)-SECO at 5.8 mg kg/day significantly decreased their body weight gain and reduced food intake and adiposity index. The expression of SREBP-1c and FAS genes were significantly down regulated in liver with (-)-SECO. The expression of beta-oxidation-related genes, such as PPARa, CPT-1, and ACOX, in liver were up-regulated in all groups treated with (-)-SECO, (-)-END, or (-)-END. (-)-SECO may impact fatty acid synthesis by suppressing the expression of SREBP-1c and FAS genes in liver and promoting beta-oxidation of fatty acids in liver by inducing the expression of beta-oxidation-related genes, such as PPARa, CPT1, and ACOX.

ABSTRACT:

Flaxseed lignan, secoisolariciresinol has been reported to possess health benefits. We previously synthesized each stereo isomer 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 acids 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, sub cutaneous 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 (-)-enterodio promoted gene expression of acyl-CoA oxidase, carnitine palmitoyltransferase-1, and peroxisome proliferator-activated receptor a, which are related to beta-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 b-oxidation of fatty acids. (Author’s abstract)