Fat Storage Gene in Overdrive in Obese People

A gene that programs muscle tissue to store fat is over-expressed in obese women, researchers here say, and may be a key reason why dieting fails.

The gene, dubbed stearoyl-CoA desaturase 1, or SCD1, codes for an enzyme that catalyzes the synthesis of monounsaturated fatty acids. It is up-regulated in skeletal muscle taken from obese women, compared with muscle from lean women, according to Deborah Muoio, Ph.D., of Duke Medical Center.

The increased expression of the gene starts a cascade of cellular events that culminates in increased fat storage in muscle tissue, Dr. Muoio and colleagues concluded in the October issue of Cell Metabolism.

The finding links the lipid metabolism malfunctions seen in obesity and Type 2 diabetes with a genetic underpinning, Dr. Muoio said. "Obesity and Type 2 diabetes are strongly associated with abnormal lipid metabolism and the accumulation of fat droplets in muscle, but the underlying causes of these perturbations have been unknown," she said.

SCD1 is "at least a very important contributor" to those changes, she added.

"There are two important observations that might have clinical relevance," Dr. Muoio said. The first is that SCD1 and any other mechanisms that mediate obesity-associated changes in muscle lipid metabolism provide a possible target for drug development, she said in an interview.

The second observation is that muscle cells from obese subjects - even after several generations of growth outside the body - still store more fat than cells from lean subjects, she said.

"That tells us that the program is being perpetuated even in the absence of the obese environment," Dr. Muoio said, "and the implication there is that it may explain why certain individuals have difficulty losing weight or maintaining weight loss."

Using DNA micro-array technology, the researchers compared tissue from the rectus abdominis muscle of eight women whose body mass index (BMI) was greater than 35 to similar tissue from eight women with a body mass index of less than 25.

In a previous study, the researchers had shown that the obese individuals were not yet diabetic, but did exhibit severe insulin resistance; their muscle was interlaced with fat droplets and they also had a 43% decrease in their ability to metabolize fat, compared with lean individuals.

In this study, the DNA micro-array technology showed that the muscle tissue of the obese women had roughly three times the levels of SCD1 than the muscle of the lean women. The obese women had 3.48 times (plus or minus 1.25) the SCD1 of the lean women; the difference was statistically significant at the p<0.05 confidence level.