Manipulating dietary composition to prevent diaphragm sarcopenia in heart failure

Bowen, T and Hendrickse, P and Pereira, M and Storey, E and Scalabrin, M and Wheatcroft, S and Roberts, L and Yuldasheva, N (2026) Manipulating dietary composition to prevent diaphragm sarcopenia in heart failure. European Journal of Preventive Cardiology, 33 (Supple): 240.479. ISSN 2047-4873

Abstract

Introduction Chronic heart failure (CHF) is characterised by the main symptom of exercise intolerance and sarcopenia (i.e. loss of muscle mass and strength). Respiratory muscle sarcopenia is closely associated with worse symptoms and highlighted as a potential therapeutic target in CHF, although treatments remain limited. The obesity paradox in CHF indicates obese compared to non-obese patients have more protection against mortality, but whether this is associated with less diaphragm sarcopenia remains unclear. This study, therefore, aimed to test whether high fat diet (HFD)-induced obesity could protect against diaphragm sarcopenia in a mouse model of CHF. Methods and Results At 12 weeks of age, male C57/BL6 mice were randomised to sham (n=10), HFD (n=11), myocardial infarction (MI) (N=7), or MI+HFD (N=7). MI was induced via ligation of the left coronary artery. Mice were assessed 10 weeks after surgery, with cardiac function (echocardiography) and diaphragm function (isolated bundles; in vitro) assessed. The left-ventricular ejection fraction (LVEF) was reduced (P<0.05) to 28±14 and 19±10 % in MI and MI+HFD groups, respectively, vs controls (75±7 %) and HFD (68±9 %). Body mass was higher (P<0.05) in HFD (42.6±5.4 g) and MI+HFD (41.2±1.7 g) vs control and MI groups (32±3.8 g and 29.7±4.6 g). Peak diaphragm contractile force showed the greatest reductions in MI by ~40%, but this was attenuated in MI+HFD (P<0.05). Furthermore, repeating the experiments but with HFD administered for 6 weeks before MI surgery also protected against subsequent diaphragm dysfunction (P<0.05). Serum concentrations of TNFα were increased (P<0.05) by ~50% in MI vs controls, but this was attenuated in MI+HFD (P>0.05). Subsequent in vivo experiments in treated mice (N=5) then confirmed a direct role for TNFα administration to directly reduce diaphragm function by around 50% (P<0.05). Conclusions An acute high fat diet, administered either before or after myocardial infarction to induce CHF, protected against diaphragm sarcopenia. Preservation of diaphragm function with a HFD was associated with a shift away from a pro-inflammatory state and lower cytokine TNFα levels, highlighting a potential role of systemic factors in diaphragm sarcopenia in CHF.