Combined ASBT Inhibitor and FGF15 Treatment Improves Therapeutic Efficacy in Experimental Nonalcoholic Steatohepatitis

Abstract

mediate weight loss and metabolic improvement. Further clinical studies may be warranted to investigate whether combining ASBT inhibitor and FGF19 analogue enhances anti-NASH efficacy and reduced treatment-associated adverse events in humans.

Flavonoids from Whole-Grain Oat Alleviated High-Fat Diet-Induced Hyperlipidemia via Regulating Bile Acid Metabolism and Gut Microbiota in Mice

“…The inhibition of ABST in the intestine to treat hypercholesterolemia has attracted considerable pharmaceutical interest. 17 The present work aimed to investigate whether FO could regulate HFD-induced hyperlipidemia through the interaction between BA metabolism and gut microbiota. The expression of essential genes and proteins in lipid and BA metabolism was determined via real-time qualitative polymerase chain reaction (RT-qPCR) and Western blot assays.…”

“…Blocking intestinal BA reabsorption causes a compensatory induction of BA synthesis, leading to cholesterol-lowering. The inhibition of ABST in the intestine to treat hypercholesterolemia has attracted considerable pharmaceutical interest …”

Reduction in the risk of major adverse cardiovascular events with the BET protein inhibitor apabetalone in patients with recent acute coronary syndrome, type 2 diabetes, and moderate to high likelihood of non-alcoholic fatty liver disease

“…Considerable investigation is ongoing worldwide to find safe and efficacious therapies to treat NAFLD so as to prevent hepatic injury and attenuate risk for CVD. Many classes of drugs are being tested for efficacy and safety [51] , [52] , [53] .…”

Bile Acid Sequestrants for Hypercholesterolemia Treatment Using Sustainable Biopolymers: Recent Advances and Future Perspectives

“…In that regard, an alternative approach to luminal sequestration of bile acids is reported and found efficacious for the pharmacotherapy approach of direct inhibition of ileal apical sodium-dependent bile acid transporter (ASBT). − The ASBT, also called IBAT, ISBT, or ABAT (a 348 amino acid membrane glycoprotein with a glycosylated extracellular amino terminus and cytosolic carboxyl terminus, indicating an odd number of transmembrane domains), is expressed at tissue sites and is responsible for the uptake of the BAs/BSs across the enterocyte brush border membrane. − ASBT inhibitors are the nonsystemic molecules that act locally at the ASBT site and have been shown to be effective in reducing LDL cholesterol in many recent studies. − The ASBT inhibitor is approved for use in the treatment of chronic constipation, , and several powerful ASBT inhibitors are in preclinical and clinical development for the treatment of cholestatic liver disease/pruritus , and safe to use for patients with type 2 diabetes mellitus (T2DM) . One of the potential side effects of these ASBT inhibitors would be the induction of diarrhea due to the triggering of malabsorption of the BAs/BSs. ,,, …”