INTESTINAL ABSORPTIVE CAPACITY AS A MECHANISTIC DRIVER OF OBESITY AND TYPE 2 DIABETES: INTEGRATIVE FRAMEWORK AND DEVELOPMENT OF THE ABSORPTIVE CAPACITY INDEX

Obesity and type 2 diabetes (T2D) are multifactorial disorders commonly attributed to excess caloric intake and insufficient expenditure. However, these paradigms overlook a critical determinant of systemic energy flux—the intestinal absorptive capacity (IAC). We hypothesize that IAC is a quantifiable, plastic, and modifiable biological trait that causally contributes to obesity and T2D by enhancing nutrient uptake and activating maladaptive endocrine, bile acid, and microbiome-mediated feedback loops.
We propose the development of an Absorptive Capacity Index (ACI) integrating nutrient uptake kinetics, transporter expression, gut hormone secretion, intestinal permeability, and microbial activity. Mechanistically, elevated IAC leads to increased glucose and lipid absorption, exaggerated incretin secretion with receptor desensitization, bile acid–FXR/TGR5 dysregulation, barrier dysfunction, and microbial reinforcement of absorptive function. Collectively, these processes amplify systemic nutrient flux and metabolic stress.
Therapeutic modulation of IAC—through transporter inhibition, bile acid sequestration, microbiome-directed therapies, or surgical interventions—offers a novel strategy to reduce effective energy absorption, restore metabolic balance, and redefine metabolic disease through the lens of intestinal energy efficiency.