title: Cardiolipin profiles as a potential biomarker of mitochondrial health in diet-induced obese mice subjected to exercise, diet-restriction and ephedrine treatment.
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.
authors.affiliation: Department of Comparative Pathobiology, Purdue University, West Lafayette, IN, 47907, USA.
authors.forename: Catherine
authors.initials: C
authors.lastname: Faber
authors.forename: Zhaohai J
authors.initials: ZJ
authors.lastname: Zhu
authors.forename: Stephen
authors.initials: S
authors.lastname: Castellino
authors.forename: David S
authors.initials: DS
authors.lastname: Wagner
authors.forename: Roger H
authors.initials: RH
authors.lastname: Brown
authors.forename: Richard A
authors.initials: RA
authors.lastname: Peterson
authors.forename: Lisa
authors.initials: L
authors.lastname: Gates
authors.forename: Joanna
authors.initials: J
authors.lastname: Barton
authors.forename: Mark
authors.initials: M
authors.lastname: Bickett
authors.forename: Laura
authors.initials: L
authors.lastname: Hagerty
authors.forename: Carie
authors.initials: C
authors.lastname: Kimbrough
authors.forename: Mario
authors.initials: M
authors.lastname: Sola
authors.forename: David
authors.initials: D
authors.lastname: Bailey
authors.forename: Holly
authors.initials: H
authors.lastname: Jordan
authors.forename: Chandikumar S
authors.initials: CS
authors.lastname: Elangbam
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D031204:Caloric Restriction; D002308:Cardiolipins / Q000378:metabolism*; D002853:Chromatography, Liquid; D004032:Diet; D004809:Ephedrine / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism*; D010805:Physical Conditioning, Animal; D053719:Tandem Mass Spectrometry
chemical_list: D015415:Biomarkers; D002308:Cardiolipins; D004809:Ephedrine
keywords: brown adipose tissue; cardiolipin; ephedrine; exercise; mitochondrial health; skeletal muscles