Elevated Myocardial Fructose and Sorbitol Levels Are Associated with Diastolic Dysfunction in Diabetic Patients, and Cardiomyocyte Lipid Inclusions in Vitro

Overview

Journal Nutr Diabetes

Specialties Endocrinology
Nutritional Sciences

Date 2021 Feb 9

PMID 33558456

Citations 9

Authors

Lorna J Daniels

Marco Annandale

Parisa Koutsifeli

Xun Li

Carol T Bussey

Isabelle van Hout

Richard W Bunton

Philip J Davis

Sean Coffey

Rajesh Katare

Regis R Lamberts

Lea M D Delbridge

Kimberley M Mellor

Affiliations

Soon will be listed here.

Abstract

Diabetes is associated with cardiac metabolic disturbances and increased heart failure risk. Plasma fructose levels are elevated in diabetic patients. A direct role for fructose involvement in diabetic heart pathology has not been investigated. The goals of this study were to clinically evaluate links between myocardial fructose and sorbitol (a polyol pathway fructose precursor) levels with evidence of cardiac dysfunction, and to experimentally assess the cardiomyocyte mechanisms involved in mediating the metabolic effects of elevated fructose. Fructose and sorbitol levels were increased in right atrial appendage tissues of type 2 diabetic patients (2.8- and 1.5-fold increase respectively). Elevated cardiac fructose levels were confirmed in type 2 diabetic rats. Diastolic dysfunction (increased E/e', echocardiography) was significantly correlated with cardiac sorbitol levels. Elevated myocardial mRNA expression of the fructose-specific transporter, Glut5 (43% increase), and the key fructose-metabolizing enzyme, Fructokinase-A (50% increase) was observed in type 2 diabetic rats (Zucker diabetic fatty rat). In neonatal rat ventricular myocytes, fructose increased glycolytic capacity and cytosolic lipid inclusions (28% increase in lipid droplets/cell). This study provides the first evidence that elevated myocardial fructose and sorbitol are associated with diastolic dysfunction in diabetic patients. Experimental evidence suggests that fructose promotes the formation of cardiomyocyte cytosolic lipid inclusions, and may contribute to lipotoxicity in the diabetic heart.

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