Researchers at the University of Illinois Urbana-Champaign have been able to successfully identify the previously unknown behavior of a key gut hormone that regulates gene expression in the liver and controls fat production in the body.
Gastrointestinal Hormones (GI Hormones or Gut hormones) which are secreted by cells in the stomach and small intestine play an important role in regulating fat production in the body.
Fat generation in the body
After eating, the pancreas produces insulin, which triggers the liver to convert digested foods into fat for storage in a process known as lipogenesis. A few hours later, when the body begins the transition to fasting mode, the liver slows fat production.
One of the lead professors on the study, Prof. Jongsook Kim Kemper observed that while the insulin pathway has been thoroughly studied, the pathway by which lipogenesis is turned off has largely remained unknown.
The study, lead by Prof. Jongsook Kim Kemper, a molecular and integrative physiology scholar and research scientist Young-Chae Kim, identified the gut hormone named FGF15 in mice and its human counterpart FGF19 as the key hormone which turned off fat-producing genes in the liver.
Once the body transitions from feeding to fasting, the FGF15/19 hormone activated regulatory molecules to enter the nucleus, the center of the cell where DNA is stored, and inhibit gene expression.
“This gut hormone actually acts as a breaker of insulin action, and specifically inhibits lipogenesis in the liver so that it’s tightly regulated,” Prof. Kemper remarked. “For example, with the holidays coming up, if you eat some cookies, the body will release insulin, which promotes lipogenesis. If lipogenesis is not reduced later when the body enters the fasting state, excess fat will accumulate in the liver, so the FGF19 hormone puts the brakes on fat production.”
One of the key revelations from the study was that the pathway for turning off fat production was dysregulated or uncontrolled in mice with obesity and human patients with nonalcoholic fatty liver disease as genes that the gut hormone regulates were highly active, the FGF15/19-activated regulatory molecules did not even enter the cell’s nucleus and the suppression markers were not added to the genes.
Emphasizing the importance of the study, Prof Kemper stated that “This study could be very important for understanding this pathway and investigating how it is abnormal in obesity and nonalcoholic fatty liver disease.” while adding that “It adds to our understanding of obesity, nonalcoholic fatty liver disease and other metabolic disorders. It also could have implications for other diseases such as diabetes or certain cancers, for which obesity is a risk factor.
“Based on this study, we potentially could search for therapeutic treatment options to target this pathway and increase regulatory function,” Prof Kemper concluded.
The critical study was published in the journal Nature Communications.