News & Research

By: Felicia Breedy

American Diabetes Association-funded researcher Gökhan Hotamisligil, MD, PhD, and his postdoctoral fellow Masato Furuhashi, MD, PhD, have published results in the February 5, 2010 edition of the journal Cell that specifically links inflammation, mediated by the immune system and metabolism. The study was conducted at the Harvard School of Public Health in Boston, Massachusetts.

Gokhan Hotamisligil

 
Previous studies in Dr. Hotamisligil's laboratory demonstrate the occurrence of inflammation in mice as well as in humans for diseases such as obesity, type 2 diabetes, and heart disease. Now, compelling evidence points to a process called metaflammation. This process is triggered by the metabolism of nutrients when the body processes food into energy. However, in excess quantities, these nutrients can be detrimental. PKR is a mechanism by which necessary and beneficial nutrients can cause damage to cells and organs. The basis for these mechanisms remains to be understood and continue to be investigated.

Dr. Hotamisligil explains, "When mice eat a normal diet, a molecule named PKR (RNA-dependent protein kinase) is silent. However, if a cell containing PKR is bombarded with too many nutrients, PKR grabs other immune system molecules that respond to this attack and organizes a firing squad to shoot down normal processes, leading to insulin resistance and metabolic dysfunction."

Researchers will now focus on the identifying which nutrients cause adverse effects. "One of the difficulties in understanding how our diet is integrated into disease risk is our inability to understand what specific component of a diet is actually regulating particular responses in humans," says Dr. Hotamisligil. "So the discovery of this molecule actually gives us a very specific way to identify the harmful components of the diet."

Results from follow up studies are pending, after which clinical trials would be conducted to find the potential drug or nutrients that could regulate PKR.
 
(Takahisa Nakamura, Masato Furuhashi, Ping Li, Haiming Cao, Gurol Tuncman, Nahum Sonenberg, Cem Gorgun, and Gökhan Hotamisligil. Double-stranded RNA-dependent Protein Kinase Links Pathogen Sensing with Stress and Metabolic Homeostasis. Cell, February 5, 2010)