By Rich Haridy
A fascinating new study, published in the prestigious journal Nature Communications, is shedding light on a previously unknown mechanism by which a hormone released from the gut in the hours after eating effectively switches off the body’s fat production processes. The research also found this regulatory mechanism is defective in obese mice and human patients with non-alcoholic fatty liver disease.
After we eat a meal our body gets down to serious metabolic business. One key process triggered by eating is called lipogenesis, which is when our liver begins converting food into fats for storage across the body.
Lipogenesis is stimulated by insulin, a well-known hormone released by the pancreas, and this particular metabolic pathway has been well-studied. However, it is still unknown exactly what happens a few hours after eating when the liver begins to slow fat production.
It had previously been hypothesized that lipogenesis eventually slows as insulin stimuli decreases in the hours after eating a meal. This new research suggests lipogenesis is not passively suppressed by decreasing insulin levels but instead it is actively repressed by a hormone released from the gut.
A team led by Jongsook Kim Kemper from the University of Illinois Urbana-Champaign found a gut hormone called FGF19 (or FGF15 in mice, hence the oft-used term FGF15/19) is produced in the hours after eating. FGF15/19 was seen to directly suppress the gene activity in the liver associated with lipogenesis.
“This gut hormone actually acts as a breaker of insulin action, and specifically inhibits lipogenesis in the liver so that it’s tightly regulated,” explains Kemper. “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.”
Prior studies have shown levels of FGF15/19 generally peak in the blood around three hours after eating, at a point where insulin levels have returned to baseline. The researchers suggest this means the mechanism plays a role in transitioning the body from a fed state to a fasting state.
The new study also investigated FGF15/19 activity in human patients with non-alcoholic fatty liver disease and in obese mice. In both instances the researchers identified significant abnormalities in this mechanism, finding the gut hormone ineffective in tamping down the gene activity necessary to effectively switch off lipogenesis.
“This study could be very important for understanding this pathway and investigating how it is abnormal in obesity and nonalcoholic fatty liver disease,” says Kemper. “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.”
In the published study the researchers do note there may be more undiscovered regulatory pathways that contribute to the switching on and off of lipogenesis but it is clear FGF15/19 certainly plays a major role in this fed-to-fasting metabolic transition. It is still very early days for the research and it’s unclear whether this particular pathway can be therapeutically targeted but it is a promising new discovery.
The new study was published in the journal Nature Communications.