Cardiac Mitochondrial Phospholipid Acyl Chains are Remodeled in Murine Obesity but do not Impair Supercomplex Formation, Respiratory Enzyme Activity, or Respiration

Abstract

Cardiac phospholipids, notably cardiolipin, undergo acyl chain remodeling and/or loss of content in diseases such as aging, diabetes and cardiovascular disease. Acyl chain remodeling and loss of content are postulated to mediate mitochondrial dysfunction in these disease states. Surprisingly, less is known about how diet‐induced obesity influences phospholipid acyl chain composition and thereby mitochondrial responses. Here we tested if a high fat diet remodeled murine cardiac phospholipid acyl chain composition and the mitochondrial response. Several mitochondrial endpoints were assayed in response to a high fat diet. We found that mice consuming a high fat diet displayed 0.2–3.3 fold changes in acyl chain remodeling of cardiolipin, phosphatidylcholine, and phosphatidylethanolamine, measured via LC/MS, but no change in total phospholipid mass. Analysis of monolayers constructed using a Langmuir trough from the mitochondrial phospholipids of obese mice revealed an accompanying impairment in the packing properties of the membrane. Although there were alterations in the mitochondrial membrane composition and organization, the high fat diet, relative to the lean controls, had no influence on cardiac mitochondrial supercomplex formation, respiratory enzyme activity, or respiration. These effects were tissue specific however, since complex I to III liver respiratory enzyme activity was diminished with the high fat diet compared to the control diet. These results suggest that diet‐induced obesity leads to modest acyl chain remodeling of mitochondrial phospholipids but does not disrupt mitochondrial supercomplexes, respiratory enzyme activity, or respiration in the heart. Altogether, our findings support an emerging view suggesting that mitochondrial acyl chain remodeling is not a major driver of disrupting mitochondrial function.Support or Funding InformationFunding supported by NIH R15HL12292201 (SRS and DAB) and NIH R01HL123647 (SRS and DAB).