MMRI Study Challenges Assumptions About Fatty Liver Disease and Heart Failure

UTICA, N.Y. – Researchers at MMRI have published new findings demonstrating that diet-related steatohepatitis, commonly known as fatty liver disease, does not independently lead to heart failure with preserved ejection fraction (HFpEF), a condition marked by impaired heart relaxation despite normal pumping ability and that can occur in the presence of comorbidities such as obesity and high blood pressure.

This development, reported in a new article published in PLOS One by Zhiqiang Lin, Ph.D., associate professor, and Chase Kessinger, Ph.D., assistant professor, both in the biomedical research and translational medicine department at MMRI, indicates that additional stressors are necessary for HFpEF to develop in patients with metabolic dysfunction associated steatohepatitis (MASH).

This study investigated the effects of two formulated diets: high-fat only or high-fat with added fructose and cholesterol, indicative of a HFpEF diet, on organ health and metabolism. In turn, this enabled the researchers to study how these dietary components contribute to the induction of obesity and its relationship to heart disease, specifically in the development of HFpEF. For patients suffering from fatty liver disease and who may be at risk of developing HFpEF, this study highlights a deeper understanding of the condition, its causes, and opens the door for possible treatments.

“This study’s findings show that the HFpEF diet, which is similar to our western-style diet is more harmful than a regular high-fat diet alone, particularly with respect to metabolic dysregulation, suggesting that fat, by itself, does not harm heart muscle cells,” said Dr. Lin.

“A fatty liver alone does not appear to be enough to cause HFpEF in our models, and while the human condition and our diets are complex, these results point to the need to identify the additional drivers of cardiac dysfunction in at-risk patients with fatty liver disease, one of which is hypertension or high blood pressure,” said Dr. Kessinger.

“With roughly five percent of adults in the United States suffering from MASH, we are excited that these findings support the potential for new therapeutics in regard to treatment of this disease,” said Maria I. Kontaridis, Ph.D., executive director, Gordon K. Moe professor and chair of biomedical research and translational medicine at MMRI. “This study further positions MMRI as a world-renowned leader in cardiovascular research.”

The study, “Diet-induced steatohepatitis does not cause heart failure with preserved ejection fraction in male middle-aged C57BL/6N mice,” is available online in PLOS One [https://doi.org/10.1371/journal.pone.0339642].

MMRI scientists who contributed to the study include Zhiqiang Lin, Ph.D., Chase W. Kessinger, Ph.D., Lin Chen, Ph.D., Felicia Huang, Jierui Lin, and Amanda Davenport.