Dietary supplementation with evodiamine prevents obesity and improves insulin resistance in ageing mice

• Effects of long-term dietary supplementation with evodiamine on obesity and longevity were investigated in ageing mice.
• Evodimaine prevented body weight gain in middle age but did not increase lifespan.
• Chronic ingestion of high dose evodiamine (10 mg/kg food) caused excessive reduction in body weight.
• Evodiamine increased AMPK phosphorylation and down-regulated mTOR signalling in white adipose tissue.
• Evodiamine at a low dose (1 mg/kg food) prevents obesity and insulin resistance even when ingestion begins in middle age.

Evodiamine is a major alkaloid extracted from the fruit of Evodia fructus, which reduces diet-induced obesity in young animals. We investigated the effects of long-term dietary supplementation with evodiamine on obesity, insulin resistance and longevity in normal ageing mice. Twelve-month-old C57BL/6J male mice were fed with standard chow with or without 1 or 10 mg evodiamine per kg food and maintained until death. Supplementation with low dose evodiamine prevented body weight gain and improved glucose tolerance in the mice, in which increased AMPK phosphorylation and down-regulation of mTOR signalling responsible for regulating energy metabolism were detected in white adipose tissue. However, evodiamine supplementation did not increase lifespan, and the high dose evodiamine caused excessive reduction in body weight, which could have side effects in aged animals. Thus, evodiamine at a low dose (1 mg/kg food) prevents obesity and insulin resistance even when ingestion begins in middle age.