Graphic abstract. Credit: Molecular metabolism (2023). DOI: 10.1016/j.molmet.2023.101744
Over 40% of Americans are considered obese, and the trend continues to grow. Treatments or preventive options for obesity and obesity-related diseases are limited. This is a major national healthcare and public health burden that significantly increases 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 & Avedisian School of Medicine has identified a novel drug-signaling molecule implicated in obesity, a previously unknown protein (MINAR2) discovered in 2020 in the associate professor’s lab of Pathology and Laboratory Medicine Nader Rahimi, Ph.D.
“This discovery may help unravel new aspects of the mechanisms of obesity and diabetes, which could lead to the development of novel therapies for the prevention and treatment of obesity and diabetes,” said Rahimi, corresponding author. of the article titled “Inactivation of Minar2 in Mice Hyperactivates mTOR Signaling and Results in Obesity” and published online in Molecular metabolism.
To investigate the role of MINAR2 in obesity, the research team generated global MINAR2 knockout animal models that knocked out the function of this gene. MINAR2-deficient animal models fed a normal non-high-fat diet showed an increased fat mass ratio 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. .
Researchers found that mammalian target of rapamycin (mTOR) signaling that regulates metabolism and other cellular processes such as cell proliferation and autophagy is hyperactivated in fat cells from MINAR2-deficient animal models. MINAR2 interacts with raptor, a specific and essential component of the mTOR 1 complex and is a negative physiological regulator of mTOR signaling with an important role in obesity and metabolic disorders.
“Anti-obesity therapy has proven difficult and most anti-obesity drugs to date have poor or insufficient efficacy with questionable safety. MINAR2 is a drug molecule and drugs that target MINAR2 could lead to the development of effective treatments,” Rahimi said. “Controlling 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. .”
Saran Lotfollahzadeh et al, Knockout of Minar2 in mice overactivates mTOR signaling and results in obesity, Molecular metabolism (2023). DOI: 10.1016/j.molmet.2023.101744
Provided by Boston University School of Medicine
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