Energy and macronutrient restriction regulate bile acid homeostasis

Area of Science:

• Metabolism and Nutrition
• Gastroenterology
• Endocrinology

Background:

• Caloric restriction (CR) previously shown to increase intestinal bile acid (BA) concentration.
• Investigating nutrition-related factors that modulate BA levels under dietary interventions.

Purpose of the Study:

• To elucidate the mechanisms behind increased BA levels in mice under various dietary restrictions.
• To identify specific dietary components and energy restriction's role in BA homeostasis.

Main Methods:

• Male mice were subjected to different restrictive diets (CR, intermittent fasting, fasting-mimicking diet, low-carbohydrate, ketogenic).
• Measured BA concentrations in liver, plasma, and feces.
• Assessed gene and protein expression of key BA synthesis and transport factors (Shp, Cyp27a1, Bal, Ntcp, CYP7A1).

Main Results:

• CR increased liver BA concentration, linked to reduced Shp expression and altered mRNA/protein levels of BA synthesis/transport genes.
• Decreased fecal BA, increased plasma BA, and upregulated ileal BA transporters suggest enhanced intestinal BA uptake in CR mice.
• Prolonged energy restriction (CR, intermittent fasting, fasting-mimicking diet) increased BA levels, while overnight fasting had minimal effect.
• Low-carbohydrate/ketogenic diets raised liver BA but not intestinal BA; carbohydrate restriction alone stimulated liver BA synthesis.

Conclusions:

• Energy restriction, particularly prolonged forms, is crucial for increasing intestinal BA levels and enhancing their uptake.
• Specific dietary manipulations like carbohydrate restriction impact BA synthesis and balance differently in the liver versus the intestine.