Gastroenterology

Blocking the action of an enzyme involved in protein digestion may improve metabolic health, according to a new study published ahead of print in the American Journal of Physiology Gastrointestinal and Liver Physiology. The paper is chose as an APS select article for May. Trypsin an enzyme that bonds to proteins is the primary enzyme responsible for digesting protein in the digestive tract.

Primary enzyme responsible

Drugs (called serine protease inhibitors) that prevent enzymes such as trypsin from working have been found to reduce weight gain, high blood sugar and high cholesterol in rats. However, the process in which serine protease inhibitors improve metabolic health is not well understood.

Researchers from Janssen R&D in Pennsylvania looked at the effects of varied dosages of camostat, a serine protease inhibitor used to treat pancreatitis in Japan, on overweight mice. They found that one week of drug treatment reduced the amount of food the animals ate and led to weight loss. In addition, blood sugar levels and liver function improve when compare to animals that were simply given the same reduce amount of food.

Hormone fibroblast growth

This suggested that in addition to caloric restriction, other factors contributed to the metabolic improvements. Bloodwork performed before and after the experiment showed that the mice had higher levels of the hormone fibroblast growth factor 21 (FGF21) during treatment. FGF21 is a hormone that suppresses appetite and manages metabolism; weight loss and glucose levels. In previous studies; FGF21 rapidly increased in mice that followed a protein-restricted diet.

The research team also found that drug treatment activated a signaling pathway called the integrated stress response (ISR); which in turn caused FGF21 levels to rise. ISR can be trigger by a number of physiological stresses, including amino acid or protein deprivation. In this study, however, the dietary protein fed to mice is not restrict; but camostat tricked their bodies into thinking it was; which activated the ISR.

Achieving optimal metabolic

This finding is important because it sheds light on a new mechanism that links ISR and FGF21 in response to trypsin inhibition; the researchers explained. Because “Trypsin inhibition could be a way to enhance [FGF21 production]; resulting in beneficial effects,” they wrote. New research shows that an “alarmingly low” number of American adults are achieving optimal metabolic health; leaving the majority of people at increased risk for serious diseases.
In a study published last month in the journal Metabolic Syndrome and Related Disorders; researchers from the University of North Carolina at Chapel Hill evaluated data from 8,721 adults from the 2009 to 2016 National Health and Nutrition Examination Survey (NHANES). They found that just 1 in 8 adults in the United States have optimal metabolic health