Obesity affects millions worldwide and drives health conditions such as heart disease, diabetes, and many cancers. Now researchers from the Pennington Biomedical Research Center in Baton Rouge, LA, reported they have discovered BAM15, a protein that can be used as a potential treatment for obesity and its related diseases.
Their study, “BAM15‐mediated mitochondrial uncoupling protects against obesity and improves glycemic control,” is published in EMBO Molecular Medicine.
Currently available pharmacotherapy regimens rarely achieve weight loss of greater than 10% or provide patients with long-term weight control. An alternative approach to decreasing food intake or absorption is to decrease metabolic efficiency. Small molecule mitochondrial protonophore uncouplers decrease mitochondrial coupling efficiency resulting in increased nutrient oxidation to produce a given amount of ATP. The mitochondrial uncoupler 2,4-dinitrophenol (DNP) has been shown to have weight-loss effects in humans. However, DNP has a narrow window between effective and toxic doses.
“Obesity is a leading cause of preventable death worldwide. Despite this, current strategies for the treatment of obesity remain ineffective at achieving long‐term weight control. This is due, in part, to difficulties in identifying tolerable and efficacious small molecules or biologics capable of regulating systemic nutrient homeostasis. Here, we demonstrate that BAM15, a mitochondrially targeted small molecule protonophore, stimulates energy expenditure and glucose and lipid metabolism to protect against diet‐induced obesity,” the researchers wrote.
“Halting the obesity epidemic requires new, more effective medications. This research represents a very promising step in the discovery process. We hope that in the not-too-distant future, BAM15 or related compounds will advance to clinical drug development and become a viable treatment option for patients with obesity,” stated John Kirwan, PhD, executive director of the Pennington Biomedical Research Center.
The researchers observed BAM15 increased mitochondrial respiration and sustained activity to a great extent. Enhanced body weight regulation was observed along with reductions in fat accumulation, improvements in whole-body glucose clearance, and energy expenditure without changing body temperature. Unlike usual weight-management medications, BAM15 did not reduce the amount of food consumed, but made mitochondria less efficient.
“C57BL/6J mice treated with BAM15 were resistant to weight gain. Furthermore, BAM15‐treated mice exhibited improved body composition and glycemic control independent of weight loss, effects attributable to drug targeting of lipid‐rich tissues,” noted the researchers.
BAM15 not only made the mice resistant to weight gain but it also reduced blood sugars and insulin levels, and improved sensitivity of skeletal muscle to the effects of insulin. Skeletal muscle insulin resistance is a primary risk factor for the development of type 2 diabetes.
Their findings offer hope that BAM15 or related compounds may one day advance to clinical drug development and become an option for treating obesity and its associated diseases.
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