image: Walter J. Koch, PhD, W.W. Smith Endowed Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology, and Director of the Center for Translational Medicine at the Lewis Katz School of Medicine at Temple University. view more
Credit: Lewis Katz School of Medicine at Temple University
(Philadelphia, PA) - Like sending a letter through the mail or a text over a cellular network, the heart can generate messages that travel long distances through the body. Those messages ultimately reach fat cells, new research by scientists at the Lewis Katz School of Medicine at Temple University (LKSOM) shows.
"The ability of the heart to communicate directly with fat had been suspected, but our study is the first to provide evidence of crosstalk between heart and fat tissue that is regulated by the enzyme, G protein-coupled receptor kinase 2 (GRK2)," said senior investigator Walter J. Koch, PhD, W.W. Smith Endowed Chair in Cardiovascular Medicine, Professor and Chair of the Department of Pharmacology, and Director of the Center for Translational Medicine at LKSOM.
The findings could have implications for modulating weight gain in patients with heart failure, a condition that arises when the heart can no longer effectively pump blood through the body.
In the breakthrough paper, published online in the journal JCI Insight, Dr. Koch and colleagues show that the heart relies on a cardiac-specific messenger, the signaling enzyme, GRK2, to relay information about metabolism to fat cells.
"GRK2 signaling in the heart effectively regulates fat accumulation in the body," said Dr. Koch. "Through this pathway, the heart 'talks' to fat and alters how fat responds to certain conditions." In previous work, Dr. Koch's laboratory showed that GRK2 serves essential roles in both normal heart function and heart failure.
The researchers carried out their investigation in mice with GRK2 activity inhibited in the heart. When fed a high fat diet, GRK2-inhibited mice accumulated significantly more fat than their littermates with normal GRK2 expression. The experiment was repeated in mice with GRK2 overexpressed in the heart, mimicking the increase in GRK2 that occurs in heart failure in humans. When given a high fat diet, these mice gained less body weight compared to their normal littermates.
Using complex metabolomics, a way of investigating metabolites associated with cellular processes, Dr. Koch's team found that GRK2 signaling specifically altered branched chain amino acid (BCAA) and endocannabinoid metabolism in the heart. GRK2-overexpressing mice on high fat diets had metabolite profiles that were distinct from those of GRK2-inhibited mice and normal animals.
"We also took the work a step further and identified one BCAA metabolite that enhanced fat cell differentiation in vitro," Dr. Koch said. His team plans next to look for other metabolites and protein factors that are involved in crosstalk between the heart and fat tissue.
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The new study was made possible thanks to a prestigious $1 million Merit Award from the American Heart Association given to Dr. Koch in 2018 to investigate molecular signaling by the heart. "The Merit Award provided the funding we needed to explore the possibility that the heart acts as an endocrine organ, secreting substances that regulate distant tissues and organs," he said.
Other researchers contributing to the study include: Benjamin P. Woodall, Kenneth S. Gresham, Meryl A. Woodall, Mesele-Christina Valenti, Alessandro Cannavo, Jessica Pfleger, J. Kurt Chuprun, and Konstantinos Drosatos, Center for Translational Medicine and Department of Pharmacology, LKSOM.
The research was supported in part by National Institutes of Health grants R37HL061690, P01 HL075443, and P01 HL134608 and by American Heart Association Merit Award 18MERIT33900036.
About Temple Health
Temple University Health System (TUHS) is a $2.1 billion academic health system dedicated to providing access to quality patient care and supporting excellence in medical education and research. The Health System consists of Temple University Hospital (TUH), ranked among the "Best Hospitals" in the region by U.S. News & World Report; TUH-Episcopal Campus; TUH-Northeastern Campus; Fox Chase Cancer Center, an NCI-designated comprehensive cancer center; Jeanes Hospital, a community-based hospital offering medical, surgical and emergency services; Temple Transport Team, a ground and air-ambulance company; and Temple Physicians, Inc., a network of community-based specialty and primary-care physician practices. TUHS is affiliated with the Lewis Katz School of Medicine at Temple University, and Temple University Physicians, which is Temple Health's physician practice plan comprised of more than 500 full-time and part-time academic physicians in 20 clinical departments.
The Lewis Katz School of Medicine (LKSOM), established in 1901, is one of the nation's leading medical schools. Each year, the School of Medicine educates more than 800 medical students and approximately 240 graduate students. Based on its level of funding from the National Institutes of Health, the Katz School of Medicine is the second-highest ranked medical school in Philadelphia and the third-highest in the Commonwealth of Pennsylvania. According to U.S. News & World Report, LKSOM is among the top 10 most applied-to medical schools in the nation.
Temple Health refers to the health, education and research activities carried out by the affiliates of Temple University Health System (TUHS) and by the Katz School of Medicine. TUHS neither provides nor controls the provision of health care. All health care is provided by its member organizations or independent health care providers affiliated with TUHS member organizations. Each TUHS member organization is owned and operated pursuant to its governing documents.
Journal
JCI Insight