A University of Michigan Health System study provides new clues about the health-damaging molecular changes set in motion by eating high fat foods.
A better understanding of the body’s response to indulgent eating could lead to new approaches for treating diabetes and metabolic syndrome. High fat foods can contribute to obesity, which increases the risk for developing type 2 diabetes.
The researchers learned a key protein called Bcl10 is needed for the free fatty acids, found in high fat food and stored in body fat, to impair insulin action and lead to abnormally high blood sugar.
In the laboratory study, mice deficient in Bcl10 were protected from developing insulin resistance when fed a high-fat diet. The findings were published online ahead of print in the May 31 issue of Cell Reports.
Insulin helps control blood sugar, but insulin resistance can lead to the abnormally high blood sugar levels that are the hallmark of diabetes. Insulin resistance also plays a role in metabolic syndrome, a cluster of conditions that increase the risk for type 2 diabetes and heart disease.
As millions of Americans become overweight and obese, both type 2 diabetes and metabolic syndrome are on the rise.
“The study also underscores how very short-term changes in diet such as high-fat eating for only a few days, perhaps even less, can induce a state of insulin resistance,” says senior study author Peter C. Lucas, M.D., Ph.D., associate professor of pathology at the University of Michigan.
Researchers began by investigating how free fatty acids induce inflammation and impair insulin action in the liver. It’s thought the liver is a major target for the harmful effects of free fatty acids.
In the liver, free fatty acids undergo metabolism to produce diacylglycerols prior to inducing the inflammatory response. Diacylglycerols also activates NF-kB signaling which has been linked with cancer and metabolic and vascular diseases.
The team of researchers concluded that Bcl10 is required for the liver cells to induce inflammation and insulin resistance. In the study, Bcl10 deficient mice showed significant improvement in regulation of blood sugar.
“We were surprised to learn that Bcl10, a protein previously known for its critical role in immune cell response to infection, also plays a critical role in the liver’s response to fatty acid,” Lucas says. “This is an example of nature co-opting a mechanism fundamental to the immune system and using it in a metabolic organ, in this case, the liver.
“These findings reveal a new and important role for Bcl10 and could lead to novel ideas for treating patients with metabolic syndrome and type 2 diabetes.”
Additional authors: Matthew Van Beek, Katherine I. Oravecz-Wilson, Phillip C. Delekta, Shufang Gu, Xiangquan Li, Xiaohong Jin, Ingrid J. Apel, Katy S. Konkle, Yongja Feng, Daniel H. Teitelbaum, and Linda M. McAllister-Lucas, M.D., of the U-M; and Jurgen Ruland, of the Institut fur Klinische Chemie und Pathobiochemie, Klinikum rechts der Isar, Technische Universitat Munchen, Munich, Germany and Laboratory of Signaling in the Immune System, Helmholtz Zentrum Munchen-Germany Research Center for Environmental Health, Neuherberg, Germany.
Reference: “Bcl10 Links Saturated Fat Overnutrition with Hepatocellular NF-kB Activation and Insulin Resistance,” Cell Reports (2012), doi:10.1016/j.celrep.2012.04.006, May 31, 2012.
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