Bile-acid-mediated decrease in endoplasmic reticulum stress: a potential contributor to the metabolic benefits of...

Area of Science:

• Metabolic Surgery
• Endocrinology
• Gastroenterology

Background:

• Bariatric surgery improves metabolic health, with increased bile acids implicated.
• Mechanisms linking bile acids to metabolic benefits post-surgery are unclear.
• Ileal interposition (IT) surgery in diabetic rats improves glucose homeostasis and increases bile acids.

Purpose of the Study:

• Investigate how post-operative bile acid increases improve glucose homeostasis after IT surgery.
• Elucidate the role of bile acids in ER stress and metabolic improvements.
• Identify specific bile acids and microbial changes contributing to IT surgery's effects.

Main Methods:

• IT surgery, sham, or no surgery in UCD-T2DM rats.
• Oral fat and glucose tolerance tests (OFTT, OGTT).
• Analysis of circulating bile acids, gut microbiota, ER stress markers, insulin signaling, and beta-cell mass.
• In vitro cell culture studies with cholic acid.

Main Results:

• IT surgery improved glucose and lipid metabolism, increasing GLP-1 secretion independently of weight or intake.
• Circulating bile acids, particularly cholic acid, increased post-IT.
• IT surgery reduced ER stress in liver, adipose, and pancreas, improving insulin signaling and beta-cell preservation.
• Cholic acid reduced ER stress in hepatocyte, adipocyte, and beta-cell lines.

Conclusions:

• Postoperative increases in circulating cholic acid contribute to improved glucose homeostasis after IT surgery.
• Amelioration of ER stress by cholic acid is a key mechanism.
• IT surgery offers a potential therapeutic strategy for type 2 diabetes via bile acid modulation and ER stress reduction.