Another Bad Rap for Sat Fats: Messing Up Muscle Metabolism

One warning sign of impending type 2 diabetes is the accumulation of fat in muscle tissue. That flab is more than just excess baggage, according to new work from Joslin Diabetes Center researchers. In a paper in the May 25 Journal of Biological Chemistry, HMS assistant professor of medicine Mary-Elizabeth Patti and colleagues show that fats, and specifically saturated fats, weigh down a key gene regulator in muscle cells. Their results show how a high-fat diet may trigger the metabolic changes seen in obesity and type 2 diabetes.

Patti and colleagues had previously found that levels of two gene activators, PGC-1 alpha and beta, were reduced in people at risk for type 2 diabetes even before they developed the disease. PGC-1 proteins regulate an array of metabolic genes responsible for proper mitochondrial function, and their levels have a major impact on energy balance. Both genes and environment affect PGC-1 expression, and thus the risk of diabetes.

In the environmental corner, obesity, overeating, and a high-fat diet all diminish PGC-1–gene expression. In their new study, Patti and coworkers searched for the specific nutrients responsible for cutting PGC-1 in muscle cells. They ruled out sugar, insulin, and excess amino acids before finding that high levels of saturated fats depressed transcription of the PGC-1 genes.

“The saturated fatty acids, also known as the ‘bad’ fats, reproduce the same pattern of gene expression in our muscle cells as we see in obesity, in people on high-fat diets, and in type 2 diabetes,” Patti said.

The net result is impaired mitochondrial function and a decreased fat-burning capacity, which could exacerbate the build-up of fat in muscle cells.

The good news is that the effects of saturated fats on PGC-1 can be reversed by giving the cells good fats, such as polyunsaturated omega-3s, by exercise, and by drugs commonly used to treat type 2 diabetes.