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 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 the senior investigator.
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 in the journal JCI Insight, researchers 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 the senior author. "Through this pathway, the heart 'talks' to fat and alters how fat responds to certain conditions." In previous work, the 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, the 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," the senior author said. The team plans next to look for other metabolites and protein factors that are involved in crosstalk between the heart and fat tissue.
Cross talk between heart and fat to control metabolism
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