Celastrol, which is derived from the Thunder God vine (Tripterygium wilfordii; pictured), causes weight loss in animal models of obesity; however, the mechanisms underlying its effects have been unclear. Now, new research published in Diabetes suggests that celastrol induces hypophagia, which results in weight loss.

Credit: Alan Gregg/Alamy Stock Photo

The researchers administered celastrol once daily for 6 days to mice with high-fat diet (HFD)-induced obesity and chow-fed mice that were not obese. They confirmed previous findings that celastrol results in reduced body weight, fat mass and lean mass in both groups of mice. They also demonstrated that celastrol reduced food intake in the HFD-fed mice, and a small reduction in food intake was also seen in the chow-fed mice.

Next, the researchers treated chow-fed leptin receptor-deficient 8-week-old mice (Lepdb) and 14-week-old leptin-deficient mice (Lepob) with celastrol. Body weight, fat mass and lean mass were unaffected in these mice, but decreased body weight, fat mass and lean mass were seen in wild-type controls that were fed chow and were treated with celastrol.

The investigators also tested the role of thermogenesis in celastrol’s effects on weight loss by assessing the expression levels of genes with protein products involved in thermogenesis. They found that celastrol upregulated the expression of Mcad and Ucp1 in brown adipose tissue and Hsf1 and Ucp1 in inguinal white adipose tissue. The expression levels of other key thermogenic genes (such as Pgc1α), however, were unaffected in these tissues. In addition, even though UCP1 levels were elevated in adipose tissue, celastrol treatment did not affect energy expenditure or basal metabolic rate, which suggests that thermogenesis was not affected by celastrol.

celastrol reduces food intake, which results in weight loss

The authors conclude that thermogenesis is not a key factor in the weight loss observed with celastrol, and instead suggest that celastrol reduces food intake, which results in weight loss. They note that celastrol was safe and efficacious in their animal models, which supports the further exploration of leptin-sensitizers such as celastrol in the development of new therapeutics for metabolic diseases.