Treatment of type 2 diabetes with thiazolidinediones can lead to excess weight gain, but the mechanisms behind this change have been unclear. In September 23 Nature Medicine, Hong-Ping Guan and colleagues at University of Pennsylvania School of Medicine, Philadelphia, US, show that TZDs activate a futile metabolic cycle in adipocytes which cause the weight gain (Nature Medicine, DOI 10.1038/nm780, September 23, 2002).

Using cultured adipocytes and adipose tissue from ob/ob mice Guan et al. observed that TZDs induced adipocyte glycerol kinase activity, stimulating glycerol incorporation into triglyceride and reducing free fatty acid secretion from the cells.

"This is surprising," the authors noted, "because it is commonly held that adipocytes lack glycerol kinase".

"These results may help to find ways to minimize side effects while boosting the therapeutic benefits of TZDs," suggest the authors.

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