The "root" of obesity in "Cell Metabolism" may be in the liver!

In a groundbreaking discovery, scientists from the University of Texas Health Sciences Center in San Antonio (UT Health San Antonio) report that inhibiting liver enzymes in obese mice reduces appetite in rodents, increases energy expenditure in adipose tissue and contributes to body weight lighten

The findings, published in the journal Cell Metabolism, provide a potential ideal drug target for treating metabolic problems such as obesity and diabetes, the authors say

"We first needed to discover the mechanism, and now that we have it, we can develop drugs to improve metabolic syndrome," said senior author Masahiro Morita, PhD, of the University of Texas Health San Antonio's Sam and Ambassop Longevity and assistant professor of molecular medicine at the Institute on Aging

"We had an enzyme inhibitor, and we wanted to increase its effect more specifically," said first author Sakie Katsumura,

The liver enzyme, called CNOT6L deadenylase, turns off messenger ribonucleic acid (mRNA), which normally carries genetic instructions from the nucleus to where the two liver proteins are made

One such protein is growth differentiation factor 15 (GDF15), which sends signals to two regions in the hindbrain to control food intake

The researchers' first CNOT6L inhibitor, iD1, stabilized GDF15 and FGF21 mRNA in the liver of obese mice and increased blood levels of both proteins

Mice treated with iD1 showed improved insulin sensitivity and lower blood sugar levels

"Targeting mRNA is a fairly novel concept in the treatment of metabolic disease," said co-author Nicolas Musi, MD, professor of medicine at UT Health San Antonio and director of the Sam and Ann Barshop Institute

Obesity, type 2 diabetes, fatty liver and related metabolic diseases have become an epidemic in Texas and the United States

According to the Centers for Disease Control and Prevention (CDC), more than 37 million Americans have diabetes

According to the Centers for Disease Control and Prevention (CDC), the prevalence of obesity in the United States is over 40% and rising

"These are very serious problems and any intervention that can treat them, including drugs, is necessary," said Dr.

Dr.

This is a comprehensive, radical paradigm change

Boosting liver mRNAs curbs appetite, body weight in obese mice