In the United States, over 40% of the population is classified as obese, a proportion that continues to escalate. Obesity, a significant contributor to a multitude of health conditions including diabetes, hypertension, cancer, and more recently, severe COVID-19, presents a major challenge to our national health care and public health systems. Despite the escalating crisis, we’re still lacking in effective preventive measures and treatments for obesity and its associated illnesses.
Researchers at the Chobanian & Avedisian School of Medicine at Boston University have made a promising discovery that could shift the landscape of obesity treatment. They have pinpointed a novel signaling molecule involved in obesity: a protein named MINAR2. This protein was only identified in 2020, courtesy of the laboratory led by Associate Professor of Pathology and Laboratory Medicine, Dr. Nader Rahimi.
Dr. Rahimi, who is also a corresponding author of the paper “Inactivation of Minar2 in Mice Hyperactivates mTOR Signaling and Results in Obesity,” published online in Molecular Metabolism, noted, “This finding can help to unravel new aspects in the mechanisms of obesity and diabetes, which could lead to the development of novel therapeutics for the prevention and treatment of obesity and diabetes.”
In order to understand MINAR2’s role in obesity, the team developed MINAR2 knockout animal models, effectively eliminating the function of the gene associated with this protein. These models, even when fed a regular diet, exhibited a higher fat mass ratio than their control counterparts. When placed on a high-fat diet, the MINAR2-deficient models gained weight more rapidly, developing obesity and impaired glucose tolerance, which is a typical sign of type 2 diabetes.
The researchers observed that the mammalian target of rapamycin (mTOR) signaling, which regulates metabolism and other cellular processes, was hyperactive in the fat cells of the MINAR2-deficient models. MINAR2 interacts with raptor, a key component of mTOR complex 1, and appears to play a significant role in regulating mTOR signaling, thus influencing obesity and metabolic disorders.
“Anti-obesity therapy has proven challenging and most of the anti-obesity medications to date have poor or insufficient efficacy with questionable safety. MINAR2 is a druggable molecule and drugs that target MINAR2 could lead to the development of effective therapeutics,” Rahimi stated. “Control of excess body fat is one of the greatest scientific and medical challenges of our time. Further basic and translational research on MINAR2 could lead to a promising therapeutic target for diet-induced obesity.”
The work conducted in this study was partially funded by a grant from the Boston University Chobanian & Avedisian School of Medicine Genome Science Institute, the Center of Cross-Organ Vascular Pathology, and NIH grants R24 GM134210, S10 OD021728, S10 OD010724.