Researchers Discover Gene’s Complex Role in Obesity, Fatty Liver and Diabetes

Researchers at the Texas A&M Health Science Center Institute of Biosciences and Technology at Houston have found that a gene in the liver and elsewhere in the body, when inhibited or increased, affects fatty liver and diabetes but does not alleviate both diseases at once.

The study is currently available online in Diabetes and will be in an upcoming issue of the journal of the American Diabetes Association.

“A general drug that inhibits this gene will cure fatty liver disease in the obese while at the same time aggravate high blood lipids, such as cholesterol and cardiovascular disease, and diabetes – even in people who control their caloric intake,” said Wallace McKeehan, Ph.D., director and professor in the Center for Cancer and Stem Cell Biology at the HSC-IBT and senior author. “A drug enhancing this gene’s activity will prevent waistline fat, heart disease and diabetes but aggravate liver disease if you overeat and are obese.”

“Take your choice with a single drug,” continued Dr. McKeehan, recommending reduced caloric intake and increased exercise as best methods to prevent fatty liver and diabetes. “Cure fatty liver disease and increase diabetes, or treat diabetes and aggravate fatty liver if you overeat and do not exercise.”

Interrelated and complex, diabetes, fatty liver disease and metabolic syndrome are increasing thanks to the rising obesity rate in the United States. Fatty liver is a little-known consequence of obesity that is most common in alcoholics. Non-alcoholic fatty liver disease in obese individuals is similar to the alcoholic version, as both result in hepatitis, cirrhosis, liver failure and hepatoma (liver cancer).

The U.S. Centers for Disease Control and Prevention estimate almost two-thirds of Americans are overweight, with a quarter qualifying as obese or “super” obese. Caused by too much caloric intake and too little exercise, obesity in children ages 6-19 has increased to 15 percent in the last decade and 10 percent in ages 2-5. The estimated cost to the U.S. economy is $122.9 billion, and developing countries like China are now seeing obesity rates rise as well.

The obesity epidemic was evident in the movie documentary “Super Size Me” directed by Morgan Spurlock, as his 30-day diet of only high-fat fast food meals resulted in early signs of liver damage.

In their study, Dr. McKeehan and his colleagues found that a liver gene receptor caused fatty liver in obese mice when fed a high-calorie, fat-filled diet designed to simulate chronic obesity in humans. Removing the gene coding for the receptor, called FGFR4, cured the fatty liver despite the mice remaining obese and on a high-fat diet.

However, while the fatty liver was resolved through this approach, the mice exhibited more severe high blood cholesterol, triglycerides and diabetes. Surprisingly, even non-obese mice with a normal body weight, when fed a normal diet, had increased waistline fat, high blood lipids and diabetes when the FGFR4 was removed.