Targeting bile-acid signalling for metabolic diseases
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beta-Klotho (encoded by Klb) is the obligate coreceptor mediating FGF21 and FGF15/19 signaling. Klb(-/-)mice are refractory to beneficial action of pharmacological FGF21 treatment including stimulation of glucose utilization and thermogenesis. Here, we inv ...
Nuclear receptors farnesoid X receptor (FXR) and small heterodimer partner (SHP) are important regulators of bile acid, lipid, and glucose homeostasis. Here, we show that global Fxr(-/-) Shp(-/-) double knockout (DKO) mice are refractory to weight gain, gl ...
Magnetic resonance spectroscopy (MRS) is a powerful tool increasingly used in biomedical research and also in clinical practice.This thesis focused on the improvements of in vivo 31P MRS and 31P magnetization transfer methods at high magnetic field (9.4T ...
A large number of glucagon-like-peptide-1(GLP-1)- and peptide-YY (PYY)-producing L cells are located in the colon, but little is known about their contribution to whole body metabolism. Since bile acids (BAs) increase GLP-1 and PYY release, and since BAs s ...
Bile acids and epithelial-derived human beta-defensins (H beta Ds) are known to be important factors in the regulation of colonic mucosal barrier function and inflammation. We hypothesized that bile acids regulate colonic H beta D expression and aimed to t ...
Federation of American Society of Experimental Biology2017
NAFLD encompasses a disease spectrum ranging from hepatic steatosis to nonalcoholic steatohepatitis (NASH), fibrosis, and finally cirrhosis, which predisposes to the development of hepatocellular carcinoma. With no approved pharmacological treatment, NAFLD ...
The systemic expression of the bile acid (BA) sensor farnesoid X receptor (FXR) has led to promising new therapies targeting cholesterol metabolism, triglyceride production, hepatic steatosis and biliary cholestasis. In contrast to systemic therapy, bile a ...
Bile acids are well-recognized stimuli of glucagon-like peptide-1 (GLP-1) secretion. This action has been attributed to activation of the G protein-coupled bile acid receptor GPBAR1 (TGR5), although other potential bile acid sensors include the nuclear far ...
The γ-glutamyl transpeptidase (GGT) enzyme plays a central role in glutathione homeostasis. Direct detection of GGT activity could provide critical information for the diagnosis of several pathologies. We propose a new molecular probe, γ-Glu-[1-(13) C]Gly, ...
Brown adipocytes regulate energy expenditure via mitochondrial uncoupling. This makes these fat cells attractive therapeutic targets to tackle the burgeoning issue of obesity, which itself is coupled to insulin resistance, type 2 diabetes, cardiovascular a ...