Premium
Cardiolipin profiles as a potential biomarker of mitochondrial health in diet‐induced obese mice subjected to exercise, diet‐restriction and ephedrine treatment
Author(s) -
Faber Catherine,
Zhu Zhaohai J.,
Castellino Stephen,
Wagner David S.,
Brown Roger H.,
Peterson Richard A.,
Gates Lisa,
Barton Joanna,
Bickett Mark,
Hagerty Laura,
Kimbrough Carie,
Sola Mario,
Bailey David,
Jordan Holly,
Elangbam Chandikumar S.
Publication year - 2014
Publication title -
journal of applied toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.784
H-Index - 87
eISSN - 1099-1263
pISSN - 0260-437X
DOI - 10.1002/jat.3030
Subject(s) - erythropoietin producing hepatocellular (eph) receptor , mitochondrion , medicine , endocrinology , mitochondrial matrix , cardiolipin , biology , lipid droplet , mitochondrial dna , brown adipose tissue , adipose tissue , biochemistry , receptor , cytosol , phospholipid , enzyme , membrane , gene , receptor tyrosine kinase
ABSTRACT Cardiolipin (CL) is crucial for mitochondrial energy metabolism and structural integrity. Alterations in CL quantity or CL species have been associated with mitochondrial dysfunction in several pathological conditions and diseases, including mitochondrial dysfunction‐related compound attrition and post‐market withdrawal of promising drugs. Here we report alterations in the CL profiles in conjunction with morphology of soleus muscle (SM) and brown adipose tissue (BAT) in diet‐induced obese (DIO) mice, subjected to ephedrine treatment (EPH: 200 mg kg –1 day –1 orally), treadmill exercise (EX: 10 meters per min, 1 h per day), or dietary restriction (DR: 25% less of mean food consumed by the EX group) for 7 days. Mice from the DR and EPH groups had a significant decrease in percent body weight and reduced fat mass compared with DIO controls. Morphologic alterations in the BAT included brown adipocytes with reduced cytoplasmic lipid droplets and increased cytoplasmic eosinophilia in the EX, DR and EPH groups. Increased cytoplasmic eosinophilia in the BAT was ultrastructurally manifested by increased mitochondrial cristae, fenestration of mitochondrial cristae, increased electron density of mitochondrial matrix, and increased complexity of shape and elongation of mitochondria. Mitochondrial ultrastructural alterations in the SM of the EX and DR groups included increased mitochondrial cristae, cup‐shaped mitochondria and mitochondrial degeneration. All four CL species (tri‐linoleoyl‐mono‐docosahexaenoyl, tetralinoleoyl, tri‐linoleoyl‐mono‐oleoyl, and di‐linoleoyl‐di‐oleoyl) were increased in the BAT of the DR and EPH groups and in the SM of the EPH and EX groups. In conclusion, cardiolipin profiling supported standard methods for assessing mitochondrial biogenesis and health, and may serve as a potential marker of mitochondrial dysfunction in preclinical toxicity studies. Copyright © 2014 John Wiley & Sons, Ltd.