New Research Identifies PTP1B as a Key Target to Protect the Heart in Obesity and High-Fat Diet Conditions

A significant breakthrough in understanding heart disease mechanisms linked to obesity has emerged from research conducted by scientists at the Masonic Medical Research Institute (MMRI). The study emphasizes the role of the enzyme protein tyrosine phosphatase PTP1B in mediating detrimental effects on cardiac health caused by high-fat diets and obesity.

Published in Science Signaling, the research reveals that PTP1B contributes to metabolic shifts within the heart that lead to dysfunction. Under dietary stress, the heart undergoes a metabolic switch from its usual reliance on fatty acid oxidation to an increased dependence on glucose metabolism. This shift results in harmful lipid accumulation, mitochondrial impairment, and the development of cardiomyopathy, a condition characterized by a thickened and less flexible heart.

In experiments using genetically modified mice, those lacking PTP1B specifically in cardiomyocytes showed remarkable resistance to these adverse changes. These mice maintained normal heart structure and function, had reduced lipid deposits, and preserved mitochondrial integrity after being subjected to a high-fat diet. Advanced analyses identified that the deletion of PTP1B maintained fatty acid metabolism and prevented excessive glucose utilization by modulating pathways involving AMPK and PKM2

"These findings unveil a novel mechanism by which a high-fat diet impairs heart function and demonstrate how inhibiting PTP1B can serve as a protective strategy," said Dr. Maria I. Kontaridis, senior author of the study. "Targeting PTP1B might offer new therapeutic avenues to prevent obesity-related heart disease, especially by supporting metabolic flexibility and preventing harmful lipid buildup."

Dr. Yan Sun, a postdoctoral researcher and study co-author, explained that PTP1B acts as a metabolic switch that encourages the heart to depend on glucose during stress, potentially worsening outcomes. Disabling this switch helps the heart remain resilient and functionally healthy.

With obesity prevalence projected to reach 50% of the U.S. population by 2030, and a growing concern about childhood obesity, these findings underscore the importance of exploring new treatments. The research positions PTP1B as a promising target for therapies aimed at preventing cardiac complications in obese and metabolic disorder-afflicted individuals.

Using a mouse model with cardiomyocyte-specific PTP1B deletion, the study demonstrated preserved heart health despite high-fat diet exposure, pointing toward promising future clinical research. The findings suggest that inhibiting PTP1B could be a critical step in developing strategies against diet-induced heart disease, helping maintain proper metabolic balance and protect cardiac function.

For more details, see the original publication: Science Signaling, 2025. Source: https://medicalxpress.com/news/2025-07-highlights-protein-tyrosine-phosphatase-ptp1b.html