Guide for Selecting Experimental Models to Study Dietary Fat Absorption

Dietary fat absorption is a complex, multi-step process involving digestion, enterocyte uptake, intracellular trafficking, re-esterification, and transport via lipoproteins into circulation. Because dietary fat absorption plays a central role in lipid homeostasis, metabolic syndrome, and fat malabsorption disorders, its study has a broad biomedical significance. However, experimental investigation of this process is technically challenging due to the short lifespan of enterocytes, the dual lymphatic and portal transport routes, and the need to trace the metabolic fate of absorbed lipids. This review summarizes and critically evaluates the major experimental systems used to study dietary fat absorption, highlighting their respective strengths, limitations, and utility. A guide for selecting the most appropriate model to study specific stages of dietary fat absorption is also presented. Ultimately, because each model carries inherent methodological constraints, integrative experimental strategies that combine complementary will be necessary to link mechanistic insights with physiological relevance.