A Gut-Centric Model of Metabolic Homeostasis

Area of Science:

• Metabolic physiology
• Gastroenterology
• Endocrinology

Background:

• Modern diet and lifestyle changes have increased global rates of insulin resistance and metabolic diseases.
• The gut's role in long-term metabolic regulation is underappreciated despite its known function as an acute nutrient sensor.
• Understanding metabolic homeostasis is crucial for addressing rising morbidity and mortality from metabolic disorders.

Purpose of the Study:

• To explore the adaptive role of the intestinal mucosa in metabolic regulation.
• To present a foregut/hindgut metabolic balance model.
• To provide a framework for understanding intestinal roles in metabolic health and disease.

Main Methods:

• Analysis of insights from bariatric surgery.
• Review of intestinal nutrient stimulation experiments.
• Development of a foregut/hindgut metabolic balance model.

Main Results:

• The intestinal mucosa plays an adaptive role in metabolic regulation.
• A foregut/hindgut model clarifies distinct roles of proximal and distal intestinal segments.
• This model informs regulation of insulin resistance, hunger/satiety, and energy balance.

Conclusions:

• The proposed intestinal metabolic balance model offers a new framework for metabolic research.
• This model can guide the development of therapies targeting intestinal signals.
• Correcting dysregulated intestinal signals may help combat the epidemic of metabolic diseases.