Gossypol Reverses Chemo Resistance

These animals and a control group with normal levels of mtGPAT1 were placed on high-fat diets.

After three weeks, mice lacking mtGPAT1 had markedly lower than normal concentrations of the liver lipid metabolites hepatic triacylglycerol and diacylglycerol. Compared to normal mice, the animals also were protected from hepatic insulin resistance. Furthermore, results published in the July 2005 issue of Cell Metabolism revealed that the mice lacking mtGPAT1 exhibited increased hepatic insulin sensitivity despite an almost 2-fold elevation in levels of hepatic acyl-CoA, a substance previously linked to insulin resistance. This finding suggests that long chain acyl-CoA's do not mediate fat-induced hepatic insulin resistance in this model, and that mtGPAT1 might serve as a novel target for treatment of hepatic steatosis and hepatic insulin resistance.

Senior author Dr. Gerald Shulman, professor of medicine at Yale University, said, "Through noninvasive measurements of hepatic triglyceride content in humans, we have learned that elevated liver fat is fairly ubiquitous in patients with poorly controlled type 2 diabetes. It has been an under-appreciated aspect of the disease.”