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Published on: June 24, 2016
Enterocytes rely on purine biosynthesis/salvage pathway to facilitate dietary fat absorption
Yu Wang1, Li Chen2,3, Yingze Ma4
1Department of Physiology, Pharmacology & Therapeutics, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ywang391@jh.edu.
Abstract:
Dietary fat absorption is among the most energy-demanding processes of nutrient uptake. Fatty acid activation, triglyceride synthesis, and the trafficking of chylomicrons through the secretory pathway - all require ATP. How enterocytes accommodate the surge in ATP consumption following fat uptake is unclear. We show that the purine biosynthesis/salvage pathway supplies necessary ATP and that Ankyrin Repeat Domain 9 (ANKRD9) couples ATP synthesis and lipoprotein trafficking. Ankrd9 regulates enzymes within the purine biosynthesis pathway to increase ATP synthesis and facilitate Golgi dynamics. Intracellular localization of ANKRD9 is lipid and ATP-dependent. Inactivation of Ankrd9 in mice reduces intestinal ATP despite intact mitochondrial and glycolytic function, alters Golgi morphology, delays ApoB/chylomicron trafficking, and causes lipid accumulation in enterocytes, along with a lean body phenotype. Taken together, the results reveal a previously unrecognized mechanism that regulates lipid absorption in enterocytes and identify ANKRD9 as a central component of this mechanism.
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