Biological and pharmacological functions of the FGF19- and FGF21-coreceptor beta klotho.

Beta klotho (KLB) is a fundamental component in fibroblast growth factor receptor (FGFR) signaling as it serves as an obligatory coreceptor for the endocrine hormones fibroblast growth factor 19 (FGF19) and fibroblast growth factor 21 (FGF21). Through the development of FGF19- and FGF21 mimetics, KLB has emerged as a promising drug target for treating various metabolic diseases, such as type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease. While rodent studies have significantly increased our understanding of KLB function, current clinical trials that test the safety and efficacy of KLB-targeting drugs raise many new scientific questions about human KLB biology.

Pharmacological inhibition of MEK1/2 signaling disrupts bile acid metabolism through loss of Shp and enhanced Cyp7a1 expression.

The RAS-MAPK signaling pathway is one of the most frequently dysregulated pathways in human cancer. Small molecule inhibitors directed against this pathway have clinical activity in patients with various cancer types and can improve patient outcomes. However, the use of these drugs is associated with adverse effects, which can result in dose reduction or treatment interruption.

A novel role for GalNAc-T2 dependent glycosylation in energy homeostasis.

Objective: GALNT2, encoding polypeptide N-acetylgalactosaminyltransferase 2 (GalNAc-T2), was initially discovered as a regulator of high-density lipoprotein metabolism. GalNAc-T2 is known to exert these effects through post-translational modification, i.e.

Mice with a deficiency in Peroxisomal Membrane Protein 4 (PXMP4) display mild changes in hepatic lipid metabolism.

Peroxisomes play an important role in the metabolism of a variety of biomolecules, including lipids and bile acids. Peroxisomal Membrane Protein 4 (PXMP4) is a ubiquitously expressed peroxisomal membrane protein that is transcriptionally regulated by peroxisome proliferator-activated receptor α (PPARα), but its function is still unknown. To investigate the physiological function of PXMP4, we generated a Pxmp4 knockout (Pxmp4) mouse model using CRISPR/Cas9-mediated gene editing.