We are consuming higher amounts of protein than ever before, yet it appears that we are missing a crucial essential protein that is contributing to obesity and impaired glucose tolerance, consequently leading to the development of type 2 diabetes.
The obesity rate in the United States exceeds 40%, and this troubling trend continues to rise. Unfortunately, the available treatments and preventive measures for obesity and related diseases are limited. This poses a significant burden on the national healthcare system and public health, greatly elevating the risk of conditions like diabetes, hypertension, cancer, and even the severity of COVID-19.
A team of researchers from the Chobanian & Avedisian School of Medicine at Boston University has made a significant breakthrough in this field. They have identified a promising signaling molecule that can be targeted by drugs to combat obesity. This molecule, known as MINAR2, was discovered in 2020 in the laboratory of Associate Professor of Pathology and Laboratory Medicine, Dr. Nader Rahimi.
The role of Major Intrinsically Disordered NOTCH2-Associated Receptor 2 (MINAR2), a protein that has received limited research attention, remains largely unknown in relation to obesity and metabolism.
The results of this study could help find “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,” remarks corresponding author Rahimi.
The findings were published in the journal Molecular Metabolism.
In order to investigate the impact of MINAR2 on obesity, the research team conducted a study using animal models with a global knockout of the MINAR2 gene, effectively disabling its function. These MINAR2-deficient animal models were fed a normal non-high fat diet, and the results showed a higher ratio of fat mass compared to control models of the same sex and age.
When the MINAR2-deficient animal models were switched to a high-fat diet (HFD), they exhibited accelerated weight gain and developed obesity accompanied by impaired glucose tolerance, a characteristic feature of type 2 diabetes.
Further analysis revealed that the fat cells of the MINAR2-deficient animal models exhibited hyperactivation of mammalian target of rapamycin (mTOR) signaling. This signaling pathway regulates various cellular processes, including metabolism, cell proliferation, and autophagy.
MINAR2 was found to interact with raptor, a specific and essential component of mTOR complex 1, serving as a physiological negative regulator of mTOR signaling. These findings emphasize the significant role of MINAR2 in 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,” adds Rahimi.
“MINAR2 is a druggable molecule and drugs that targets MINAR2 could lead to the development of effective therapeutics,” according to Rahimi.
“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.”
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