Robert N Helsley1, Francois Moreau2, Manoj K Gupta3, Aurelia Radulescu4, Brian DeBosch5, Samir Softic6,7,8. 1. Division of Pediatric Gastroenterology, Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, 40506, USA. 2. Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. 3. Islet Cell and Regenerative Medicine, Joslin Diabetes Center and Department of Medicine, Harvard Medical School, Boston, MA, 02215, USA. 4. Department of Pediatrics, University of Kentucky College of Medicine and Kentucky Children's Hospital, Lexington, KY, 40536, USA. 5. Department of Pediatrics, Washington University School of Medicine, St. Louis, MO, 63131, USA. 6. Division of Pediatric Gastroenterology, Department of Pediatrics, University of Kentucky College of Medicine, Lexington, KY, 40506, USA. samir.softic@uky.edu. 7. Section on Integrative Physiology and Metabolism, Joslin Diabetes Center, Harvard Medical School, Boston, MA, USA. samir.softic@uky.edu. 8. Department of Pharmacology and Nutritional Sciences, University of Kentucky College of Medicine, 138 Leader Ave, Lexington, KY, 40506, USA. samir.softic@uky.edu.
Abstract
PURPOSE OF REVIEW: The objective of this review is to provide up-to-date and comprehensive discussion of tissue-specific fructose metabolism in the context of diabetes, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). RECENT FINDINGS: Increased intake of dietary fructose is a risk factor for a myriad of metabolic complications. Tissue-specific fructose metabolism has not been well delineated in terms of its contribution to detrimental health effects associated with fructose intake. Since inhibitors targeting fructose metabolism are being developed for the management of NAFLD and diabetes, it is essential to recognize how inability of one tissue to metabolize fructose may affect metabolism in the other tissues. The primary sites of fructose metabolism are the liver, intestine, and kidney. Skeletal muscle and adipose tissue can also metabolize a large portion of fructose load, especially in the setting of ketohexokinase deficiency, the rate-limiting enzyme of fructose metabolism. Fructose can also be sensed by the pancreas and the brain, where it can influence essential functions involved in energy homeostasis. Lastly, fructose is metabolized by the testes, red blood cells, and lens of the eye where it may contribute to infertility, advanced glycation end products, and cataracts, respectively. An increase in sugar intake, particularly fructose, has been associated with the development of obesity and its complications. Inhibition of fructose utilization in tissues primary responsible for its metabolism alters consumption in other tissues, which have not been traditionally regarded as important depots of fructose metabolism.
PURPOSE OF REVIEW: The objective of this review is to provide up-to-date and comprehensive discussion of tissue-specific fructose metabolism in the context of diabetes, dyslipidemia, and nonalcoholic fatty liver disease (NAFLD). RECENT FINDINGS: Increased intake of dietary fructose is a risk factor for a myriad of metabolic complications. Tissue-specific fructose metabolism has not been well delineated in terms of its contribution to detrimental health effects associated with fructose intake. Since inhibitors targeting fructose metabolism are being developed for the management of NAFLD and diabetes, it is essential to recognize how inability of one tissue to metabolize fructose may affect metabolism in the other tissues. The primary sites of fructose metabolism are the liver, intestine, and kidney. Skeletal muscle and adipose tissue can also metabolize a large portion of fructose load, especially in the setting of ketohexokinase deficiency, the rate-limiting enzyme of fructose metabolism. Fructose can also be sensed by the pancreas and the brain, where it can influence essential functions involved in energy homeostasis. Lastly, fructose is metabolized by the testes, red blood cells, and lens of the eye where it may contribute to infertility, advanced glycation end products, and cataracts, respectively. An increase in sugar intake, particularly fructose, has been associated with the development of obesity and its complications. Inhibition of fructose utilization in tissues primary responsible for its metabolism alters consumption in other tissues, which have not been traditionally regarded as important depots of fructose metabolism.
Authors: Roger J Liang; Samuel Taylor; Navid Nahiyaan; Junho Song; Charles J Murphy; Ezequiel Dantas; Shuyuan Cheng; Ting-Wei Hsu; Shakti Ramsamooj; Rahul Grover; Seo-Kyoung Hwang; Bryan Ngo; Lewis C Cantley; Kyu Y Rhee; Marcus D Goncalves Journal: Cancer Metab Date: 2021-03-24
Authors: Cassandra B Higgins; Allyson L Mayer; Yiming Zhang; Michael Franczyk; Samuel Ballentine; Jun Yoshino; Brian J DeBosch Journal: Nat Commun Date: 2022-02-28 Impact factor: 14.919