Intestinal FGF15 regulates bile acid and cholesterol metabolism but not glucose and energy balance.

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.

Liouvillian exceptional points of an open driven two-level system.

We study the applicability of the Liouvillian exceptional points (LEPs) approach to nanoscale open quantum systems. A generic model of the driven two-level system in a thermal environment is analyzed within the nonequilibrium Green's function (NEGF) and Bloch quantum master equation formulations. We derive the latter starting from the exact NEGF Dyson equations and highlight the qualitative limitations of the LEP treatment by examining the approximations employed in its derivation. We find that the non-Markov character of evolution in open quantum systems does not allow for the introduction of the concept of exceptional points for a description of their dynamics. Theoretical analysis is illustrated with numerical simulations.