As obesity in America continues to rise at alarming rates, researchers are finding that diet and exercise are not the only driving factors. A new scientific review from UCLA Health explains how stress, hardship and other social challenges can reshape a person’s gut bacteria and brain performance in ways that make it harder to keep weight off. 

Following injury from a heart attack, immune cells called neutrophils release a peptide that punctures stressed heart cells and destabilizes their electrical activity. This triggers life-threatening arrhythmias. These findings offer a novel explanation – and potential therapeutic target – for these deadly cardiac events. Ischemic heart disease – cardiac damage caused by narrowed coronary arteries – is among the leading causes of death worldwide. It can lead to heart attacks and sudden cardiac death. When a coronary artery becomes blocked, cardiomyocytes experience oxygen deprivation, which disrupts their ability to manage ions like sodium and calcium, leading to dangerous electrical instability and life-threatening arrhythmias, for which there are few treatment options beyond defibrillation. Most arrhythmias occur within the first 2 days after a heart attack, which coincides with the characteristic cellular inflammatory response to the cardiac injury. Neutrophils, which are recruited in high numbers during this response, are known to interfere with normal cellular electrical conduction and are implicated in unintended tissue damage. While this highlights neutrophils as a potential target for future therapies, their full role in promoting arrhythmias isn’t fully understood.

Using mouse models of ischemic injury alongside human tissue and cell studies, Nina Kumowski and colleagues identified the peptide resistin-like molecule γ (Retnlg or RELMγ) as a key neutrophil-derived factor that promotes arrhythmias after a heart attack. According to Kumowski et al., RELMy – an antimicrobial pore-forming peptide – destabilizes heart rhythm by binding to and attacking stressed cardiomyocytes. Once bound, the peptide punctures the cardiomyocyte membranes, creating pores that alter cellular ion flux, triggering delayed depolarization, cell death, and the formation of tissue abnormalities that promote arrhythmia. In mouse models, removing RELMγ from neutrophils reduced ventricular arrhythmia 12-fold, supporting findings that the peptide drives electrical instability in the injured heart. Notably, the human homolog of this peptide, resistin (RETN), was detected in infarcted human myocardial tissue samples, and higher circulating RETN levels correlated with worse patient outcomes, highlighting its potential clinical relevance. In a related Perspective, Edward Thorp discusses the study in greater detail.