More than 40% of Americans are considered obese, and the trend continues to grow. Treatments or preventive options for obesity and obesity-associated diseases are limited. It is a major national health and public health burden, significantly increasing the risk of diseases such as diabetes, hypertension and cancer and is linked to the severity of COVID-19.
A research team from Boston University’s Chobanian and Avedisian School of Medicine has identified a new druggable signaling molecule involved in obesity, a previously unknown protein (MINAR2) discovered in 2020 in the laboratory of Associate Professor of Pathology and Laboratory Medicine Nader Rahimi, PhD.
“This discovery may help to unlock new insights into the mechanisms of obesity and diabetes, which may lead to the development of new therapies for the prevention and treatment of obesity and diabetes,” said Rahimi, corresponding author of the paper Inactivation of Minar2 in Mice Hyperactivates mTOR Signaling and Results in Obesity published online at Molecular Metabolism.
To study the role of MINAR2 in obesity, the research team generated global knockout animal models of MINAR2 that eliminated the function of this gene. MINAR2-deficient animal models fed a normal non-high-fat diet showed an increased proportion of fat mass compared to sex- and age-matched control models. When MINAR2-deficient animal models were fed a high-fat diet (HFD), they gained weight faster than control models and developed obesity with impaired glucose tolerance, a hallmark of type 2 diabetes.
The researchers found that mammalian target rapamycin (mTOR) signaling, which regulates metabolism and other cellular processes such as cell proliferation and autophagy, is hyperactivated in the fat cells of MINAR2-deficient animal models. MINAR2 interacts with raptor, a specific and essential component of the mTOR 1 complex, and is a physiological negative regulator of mTOR signaling with a significant role in obesity and metabolic disorders.
“Anti-obesity therapy has proven to be challenging and most anti-obesity drugs to date have insufficient or insufficient efficacy with questionable safety. MINAR2 is a druggable molecule and drugs that target MINAR2 could lead to the development of effective therapies,” said Rahimi . “The control of excess body fat is one of the greatest scientific and medical challenges of our time. Further basic and translational research on MINAR2 may lead to a promising therapeutic target for diet-induced obesity.”
Boston University School of Medicine