Last month marked the end of a 5-year grant for an exciting research project funded by the National Institutes of Health to the Department of Veterans Affairs to study two mitochondrial-targeted coenzyme Q (CoQ) analogs (MTQAs) as possible treatments for obesity. The project is estimated to end in 2018, but the work being conducted to date has been valuable in understanding how an MTQA could help combat obesity.
“Our proposal is highly relevant to our veterans and population in general,” wrote Dr. William Irving Sivitz, of Iowa City VA Medical Center. “The obesity epidemic is a well-recognized world-wide problem.” Obesity is a prevalent problem for veterans, and the lifestyle changes that are effective in combating obesity can be difficult to sustain. Therefore, Dr. Sivitz believes there is a need for a drug to help prevent obesity and will do so with the project, “Mitochondrial-targeted CoQ analogs: Bioenergetic Effects in Obesity.”
According to Dr. Sivitz in a previous research article, uncoupling caloric uptake from storing energy as fat mass to expending energy as heat could lead to weight loss in obese individuals. CoQ is naturally an uncoupling agent because it is an antioxidant that affects the electron transport chain during the breakdown of nutrients into energy. Unfortunately, CoQ can only poorly penetrate the membrane, eliciting the need to chemically modify CoQ with sidechains to increase mitochondrial uptake.
“The proposed work will evaluate certain chemical derivatives of natural Co-enzyme Q that are active within mitochondria to enhance energy expenditure and/or decrease energy intake,” wrote Dr. Sivitz. “We will examine their effects in cell cultures and in vivo in a rodent model of obesity.”
“We have preliminary evidence that [MTQA compounds] are effective in preventing obesity in mice,” stated Dr. Sivitz. Now, the research team is taking a step back to really understand why MTQA compounds are effective in preventing obesity in rodent models. “Our approach to addressing this issue is innovative,” continued Dr. Sivitz. “As will become clear, we will apply new and innovative methodology to look for previously unidentified mechanisms underlying the effects of MTQAs.”
Although Dr. Sivitz is not interested in developing MTQA compounds for commercial use, the outcomes of the work funded by the grant from the NIH may lead to new drugs that combat obesity.