title: Switching to a low-fat diet attenuates the intensified doxorubicin cardiotoxicity associated with high-fat feeding.
abstract: OBJECTIVE
  A high-fat diet has been shown to exacerbate the cardiotoxicity associated with the chemotherapy drug doxorubicin (DOX); however, it is unknown whether switching from a high-fat diet to a low-fat diet can attenuate the intensified DOX cardiotoxicity. The purpose of this study was to investigate the effects of a low-fat diet on DOX-induced cardiotoxicity in rats previously fed a high-fat diet.
  
  
  METHODS
  Male rats were randomly assigned to consume a Western diet or a low-fat diet for 6 weeks. Western diet-fed rats were then further randomized to switch to the low-fat diet (WD-LF) or continue with the Western diet (WD). One week later, WD-LF and WD received 1 mg/kg DOX per day for 10 consecutive days and continued with their diets (WD-LF + DOX, WD + DOX). LF was further randomized to receive 1 mg/kg DOX per day for 10 consecutive days (LF + DOX) or saline injections as a control (LF + SAL). Four weeks following the first injection, cardiac function was analyzed, and left ventricles were analyzed for cardiotoxicity indices.
  
  
  RESULTS
  When compared to LF + SAL and LF + DOX, WD + DOX exhibited an enhanced cardiotoxicity as evidenced by reduced septal wall thickness, fractional shortening, and sarco-endoplasmic reticulum Ca(2+) ATPase expression as well as increased left ventricular cavity dimensions, lipid peroxidation, and β-myosin heavy-chain expression. This exacerbated cardiotoxicity was not observed in WD-LF + DOX.
  
  
  CONCLUSIONS
  Switching to a low-fat diet 1 week prior to, during, and following DOX treatment attenuated the exacerbated cardiotoxicity observed in the previously Western diet-fed rats.
authors.affiliation: School of Sport and Exercise Science, University of Northern Colorado, Greeley, CO 80639, USA. david.hydock@unco.edu
authors.forename: David S
authors.initials: DS
authors.lastname: Hydock
authors.forename: Chia-Ying
authors.initials: CY
authors.lastname: Lien
authors.forename: Brock T
authors.initials: BT
authors.lastname: Jensen
authors.forename: Carole M
authors.initials: CM
authors.lastname: Schneider
authors.forename: Reid
authors.initials: R
authors.lastname: Hayward
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage / Q000009:adverse effects*; D001783:Blood Flow Velocity; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D009202:Cardiomyopathies / Q000139:chemically induced / Q000178:diet therapy* / Q000378:metabolism / Q000503:physiopathology; D003326:Coronary Circulation; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects*; D004317:Doxorubicin / Q000008:administration & dosage / Q000009:adverse effects*; D006334:Heart Function Tests; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018995:Myosin Heavy Chains / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000903:Antibiotics, Antineoplastic; D008315:Malondialdehyde; D004317:Doxorubicin; D018995:Myosin Heavy Chains; D000252:Calcium-Transporting ATPases