Key result
Diet-induced obesity in mice with chronic heart failure was associated with preserved skeletal muscle mass, mitochondrial ATP production, and insulin signaling compared to lean CHF mice (p<0.05).
Why the study?
Skeletal muscle dysfunction worsens chronic heart failure prognosis, but obesity may paradoxically be associated with preserved muscle mass, ATP production, and enhanced survival.
Does diet-induced obesity preserve skeletal muscle mitochondrial function and mass in mice with chronic heart failure?
Does diet-induced obesity preserve skeletal muscle mitochondrial function and mass in mice with chronic heart failure?
p-value: p=<0.05
Obesity preserves skeletal muscle mass and mitochondrial function in a murine model of chronic heart failure, potentially explaining the obesity paradox in CHF.
Should not yet change HF nutrition guidance; leaves open whether obesity protects skeletal muscle in patients.
Background: Skeletal muscle (SM) mitochondrial dysfunction, oxidative stress, inflammation and muscle mass loss may worsen prognosis in chronic heart failure (CHF). Diet-induced obesity may also cause SM mitochondrial dysfunction as well as oxidative stress and inflammation, but obesity per se may be paradoxically associated with high SM mass and mitochondrial adenosine triphosphate (ATP) production, as well as with enhanced survival in CHF. Methods: We investigated interactions between myocardial infarction(MI)-induced CHF and diet-induced obesity (12-wk 60% vs. standard 10% fat) in modulating gastrocnemius muscle (GM) mitochondrial ATP and tissue superoxide generation, oxidized glutathione (GSSG), cytokines and insulin signalling activation in 10-wk-old mice in the following groups: lean sham-operated, lean CHF (LCHF), obese CHF (ObCHF; all n = 8). The metabolic impact of obesity per se was investigated by pair-feeding ObCHF to standard diet with stabilized excess body weight until sacrifice at wk 8 post-MI. Results: Compared to sham, LCHF had low GM mass, paralleled by low mitochondrial ATP production and high mitochondrial reative oxygen species (ROS) production, pro-oxidative redox state, pro-inflammatory cytokine changes and low insulin signaling (p < 0.05). In contrast, excess body weight in pair-fed ObCHF was associated with high GM mass, preserved mitochondrial ATP and mitochondrial ROS production, unaltered redox state, tissue cytokines and insulin signaling (p = non significant vs. Sham, p < 0.05 vs. LCHF) despite higher superoxide generation from non-mitochondrial sources. Conclusions: CHF disrupts skeletal muscle mitochondrial function in lean rodents with low ATP and high mitochondrial ROS production, associated with tissue pro-inflammatory cytokine profile, low insulin signaling and muscle mass loss. Following CHF onset, obesity per se is associated with high skeletal muscle mass and preserved tissue ATP production, mitochondrial ROS production, redox state, cytokines and insulin signaling. These paradoxical and potentially favorable obesity-associated metabolic patterns could contribute to reported obesity-induced survival advantage in CHF.
No takes yet. Share an insight, caveat, or question.
Cappellari et al. (2020) studied Chronic heart failure and obesity (n=24). Diet-induced obesity vs. Standard 10% fat diet (lean CHF and lean sham-operated) was evaluated on Gastrocnemius muscle mass, mitochondrial ATP and ROS production, redox state, cytokines, and insulin signaling (p=<0.05). Diet-induced obesity in mice with chronic heart failure was associated with preserved skeletal muscle mass, mitochondrial ATP production, and insulin signaling compared to lean CHF mice (p<0.05).
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: