Fibroblast growth factor 15/19 (FGF15/19, mouse/human ortholog) is expressed in the ileal enterocytes of the small intestine and released postprandially in response to bile acid absorption. Previous reports of FGF15–/– mice have limited our understanding of gut-specific FGF15’s role in metabolism. Therefore, we studied the role of endogenous gut-derived FGF15 in bile acid, cholesterol, glucose, and energy balance. We found that circulating levels of FGF19 were reduced in individuals with obesity and comorbidities, such as type 2 diabetes and metabolic dysfunction–associated fatty liver disease. Gene expression analysis of ileal FGF15-positive cells revealed differential expression during the obesogenic state. We fed standard chow or a high-fat metabolic dysfunction-associated steatohepatitis–inducing diet to control and intestine-derived FGF15-knockout (FGF15INT-KO) mice. Control and FGF15INT-KO mice gained similar body weight and adiposity and did not show genotype-specific differences in glucose, mixed meal, pyruvate, and glycerol tolerance. FGF15INT-KO mice had increased systemic bile acid levels but decreased cholesterol levels, pointing to a primary role for gut-derived FGF15 in regulating bile acid and cholesterol metabolism when exposed to obesogenic diet. These studies show that intestinal FGF15 plays a specific role in bile acid and cholesterol metabolism regulation but is not essential for energy and glucose balance.
Nadejda Bozadjieva-Kramer, Jae Hoon Shin, Ziru Li, Alan C. Rupp, Nicole Miller, Stace Kernodle, Nicolas Lanthier, Paulina Henry, Nikhil Seshadri, Andriy Myronovych, Ormond A. MacDougald, Robert W. O’Rourke, Rohit Kohli, Charles F. Burant, Amy E. Rothberg, Randy J. Seeley
Usage data is cumulative from April 2024 through October 2024.
Usage | JCI | PMC |
---|---|---|
Text version | 1,691 | 257 |
366 | 81 | |
Figure | 427 | 10 |
Supplemental data | 89 | 6 |
Citation downloads | 70 | 0 |
Totals | 2,643 | 354 |
Total Views | 2,997 |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.