The (patho)physiological relation between bile acid dynamics and energy homeostasis is fascinating. Increased bile acid release in the duodenum results in enhanced fat absorption, whereas increased serum bile acid levels enhance energy expenditure, leading to body weight loss. Bile acids also dampen inflammation and their synthesis by the liver lowers (LDL) cholesterol.
Targeting bile acid signaling is, therefore, appealing to treat metabolic diseases such as diabetes and atherosclerosis. Bile acids also have a dark-side and are toxic when the accumulate in the liver. This can occur when bile flow is impaired, a condition called cholestasis
In this project we specifically study the hepatic bile acid uptake transporter NTCP (gene name SLC10A1) as an potential novel target to improve human health as it determines the duration of bile acid signaling by controlling how fast bile acids are removed from serum after a meal. NTCP also controls how much bile acid accumulates in the liver. The aim is to generate novel strategies to reduce hepatic bile acid uptake to prolong bile-acid signaling and increase energy expenditure, improve glucose handling and reduce atherosclerosis and to lower bile acid accumulation during cholestasis.
This new research line focused on serum bile acid dynamics may ultimately provide new ways to treat metabolic diseases related to disturbed bile acid, lipid, glucose and energy homeostasis.
Amsterdam UMC researchers involved in this project:
