title: Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome.
abstract: The increasing prevalence of obesity adds another dimension to the pathophysiology of testosterone (TEST) deficiency (TD) and potentially impairs the therapeutic efficacy of classical TEST replacement therapy. We investigated the therapeutic effects of selective androgen receptor modulation with trenbolone (TREN) in a model of TD with the metabolic syndrome (MetS). Male Wistar rats (n=50) were fed either a control standard rat chow (CTRL) or a high-fat/high-sucrose (HF/HS) diet. After 8 weeks of feeding, rats underwent sham surgery or an orchiectomy (ORX). Alzet miniosmotic pumps containing either vehicle, 2-mg/kg·d TEST or 2-mg/kg·d TREN were implanted in HF/HS+ORX rats. Body composition, fat distribution, lipid profile, and insulin sensitivity were assessed. Infarct size was quantified to assess myocardial damage after in vivo ischaemia reperfusion, before cardiac and prostate histology was performed. The HF/HS+ORX animals had increased sc and visceral adiposity; circulating triglycerides, cholesterol, and insulin; and myocardial damage, with low circulating TEST compared with CTRLs. Both TEST and TREN protected HF/HS+ORX animals against sc fat accumulation, hypercholesterolaemia, and myocardial damage. However, only TREN protected against visceral fat accumulation, hypertriglyceridaemia, and hyperinsulinaemia and reduced myocardial damage relative to CTRLs. TEST caused widespread cardiac fibrosis and prostate hyperplasia, which were less pronounced with TREN. We propose that TEST replacement therapy may have contraindications for males with TD and obesity-related MetS. TREN treatment may be more effective in restoring androgen status and reducing cardiovascular risk in males with TD and MetS.
authors.affiliation: Heart Foundation Research Centre (D.G.D., G.E.E., A.C.B., J.P.H., E.F.D.T.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia; School of Allied Health Science (B.R.B.), Griffith University, Gold Coast, Queensland 4222, Australia; and Cancer Molecular Pathology (A.K.L.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Donner
authors.affiliation: Heart Foundation Research Centre (D.G.D., G.E.E., A.C.B., J.P.H., E.F.D.T.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia; School of Allied Health Science (B.R.B.), Griffith University, Gold Coast, Queensland 4222, Australia; and Cancer Molecular Pathology (A.K.L.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Grace E
authors.initials: GE
authors.lastname: Elliott
authors.affiliation: Heart Foundation Research Centre (D.G.D., G.E.E., A.C.B., J.P.H., E.F.D.T.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia; School of Allied Health Science (B.R.B.), Griffith University, Gold Coast, Queensland 4222, Australia; and Cancer Molecular Pathology (A.K.L.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Belinda R
authors.initials: BR
authors.lastname: Beck
authors.affiliation: Heart Foundation Research Centre (D.G.D., G.E.E., A.C.B., J.P.H., E.F.D.T.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia; School of Allied Health Science (B.R.B.), Griffith University, Gold Coast, Queensland 4222, Australia; and Cancer Molecular Pathology (A.K.L.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Bulmer
authors.affiliation: Heart Foundation Research Centre (D.G.D., G.E.E., A.C.B., J.P.H., E.F.D.T.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia; School of Allied Health Science (B.R.B.), Griffith University, Gold Coast, Queensland 4222, Australia; and Cancer Molecular Pathology (A.K.L.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Alfred K
authors.initials: AK
authors.lastname: Lam
authors.affiliation: Heart Foundation Research Centre (D.G.D., G.E.E., A.C.B., J.P.H., E.F.D.T.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia; School of Allied Health Science (B.R.B.), Griffith University, Gold Coast, Queensland 4222, Australia; and Cancer Molecular Pathology (A.K.L.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: John P
authors.initials: JP
authors.lastname: Headrick
authors.affiliation: Heart Foundation Research Centre (D.G.D., G.E.E., A.C.B., J.P.H., E.F.D.T.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia; School of Allied Health Science (B.R.B.), Griffith University, Gold Coast, Queensland 4222, Australia; and Cancer Molecular Pathology (A.K.L.), Menzies Health Institute Queensland, Griffith University, Gold Coast, Queensland 4222, Australia.
authors.forename: Eugene F
authors.initials: EF
authors.lastname: Du Toit
mesh_terms: D050154:Adiposity / Q000187:drug effects; D045930:Anabolic Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000818:Animals; D015415:Biomarkers / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects; D004195:Disease Models, Animal; D004343:Drug Implants; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D020249:Hormone Replacement Therapy / Q000009:adverse effects; D006937:Hypercholesterolemia / Q000209:etiology / Q000517:prevention & control; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D015428:Myocardial Reperfusion Injury / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D009765:Obesity / Q000150:complications* / Q000209:etiology; D009919:Orchiectomy / Q000009:adverse effects; D011467:Prostate / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation; D017208:Rats, Wistar; D013739:Testosterone / Q000008:administration & dosage / Q000009:adverse effects / Q000172:deficiency* / Q000627:therapeutic use; D014204:Trenbolone Acetate / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D045930:Anabolic Agents; D015415:Biomarkers; D019422:Dietary Sucrose; D004343:Drug Implants; D013739:Testosterone; D014204:Trenbolone Acetate