Faculty Collaboration Database

Recent advances associated with cardiometabolic remodeling in diabetes-induced heart failure. Am J Physiol Heart Circ Physiol 2024 Dec 01;327(6):H1327-H1342

Date

10/25/2024

Pubmed ID

39453429

DOI

10.1152/ajpheart.00539.2024

Scopus ID

2-s2.0-85210105516 (requires institutional sign-in at Scopus site)

Abstract

Diabetes mellitus (DM) is characterized by chronic hyperglycemia, and despite intensive glycemic control, the risk of heart failure in patients with diabetes remains high. Diabetes-induced heart failure (DHF) presents a unique metabolic challenge, driven by significant alterations in cardiac substrate metabolism, including increased reliance on fatty acid oxidation, reduced glucose utilization, and impaired mitochondrial function. These metabolic alterations lead to oxidative stress, lipotoxicity, and energy deficits, contributing to the progression of heart failure. Emerging research has identified novel mechanisms involved in the metabolic remodeling of diabetic hearts, such as autophagy dysregulation, epigenetic modifications, polyamine regulation, and branched-chain amino acid (BCAA) metabolism. These processes exacerbate mitochondrial dysfunction and metabolic inflexibility, further impairing cardiac function. Therapeutic interventions targeting these pathways-such as enhancing glucose oxidation, modulating fatty acid metabolism, and optimizing ketone body utilization-show promise in restoring metabolic homeostasis and improving cardiac outcomes. This review explores the key molecular mechanisms driving metabolic remodeling in diabetic hearts, highlights advanced methodologies, and presents the latest therapeutic strategies for mitigating the progression of DHF. Understanding these emerging pathways offers new opportunities to develop targeted therapies that address the root metabolic causes of heart failure in diabetes.

Author List

Sharma G, Chaurasia SS, Carlson MA, Mishra PK

Author

Shyam S. Chaurasia PhD Associate Professor in the Ophthalmology and Visual Sciences department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Autophagy
Diabetes Mellitus
Diabetic Cardiomyopathies
Energy Metabolism
Epigenesis, Genetic
Fatty Acids
Heart Failure
Humans
Mitochondria, Heart
Myocardium
Oxidative Stress