Impact of Diet-Induced Obesity and Testosterone Deficiency on the Cardiovascular System: A Novel Rodent Model Representative of Males with Testosterone-Deficient Metabolic Syndrome (TDMetS)

Abstract

IntroductionCurrent models of obesity utilise normogonadic animals and neglect the strong relationships between obesity-associated metabolic syndrome (MetS) and male testosterone deficiency (TD). The joint presentation of these conditions has complex implications for the cardiovascular system that are not well understood. We have characterised and investigated three models in male rats: one of diet-induced obesity with the MetS; a second using orchiectomised rats mimicking TD; and a third combining MetS with TD which we propose is representative of males with testosterone deficiency and the metabolic syndrome (TDMetS).MethodsMale Wistar rats (n = 24) were randomly assigned to two groups and provided ad libitum access to normal rat chow (CTRL) or a high fat/high sugar/low protein “obesogenic” diet (OGD) for 28 weeks (n = 12/group). These groups were further sub-divided into sham-operated or orchiectomised (ORX) animals to mimic hypogonadism, with and without diet-induced obesity (n = 6/group). Serum lipids, glucose, insulin and sex hormone concentrations were determined. Body composition, cardiovascular structure and function; and myocardial tolerance to ischemia-reperfusion were assessed.ResultsOGD-fed animals had 72% greater fat mass; 2.4-fold greater serum cholesterol; 2.3-fold greater serum triglycerides and 3-fold greater fasting glucose (indicative of diabetes mellitus) compared to CTRLs (all p<0.05). The ORX animals had reduced serum testosterone and left ventricle mass (p<0.05). In addition to the combined differences observed in each of the isolated models, the OGD, ORX and OGD+ORX models each had greater CK-MB levels following in vivo cardiac ischemia-reperfusion insult compared to CTRLs (p<0.05).ConclusionOur findings provide evidence to support that the MetS and TD independently impair myocardial tolerance to ischemia-reperfusion. The combined OGD+ORX phenotype described in this study is a novel animal model with associated cardiovascular risk factors and complex myocardial pathology which may be representative of male patients presenting with TDMetS.

Trenbolone Improves Cardiometabolic Risk Factors and Myocardial Tolerance to Ischemia-Reperfusion in Male Rats With Testosterone-Deficient Metabolic Syndrome

“…As we have demonstrated previously with similar models (35,46), we propose that the HF/HSϩORX model used in the present study is an appropriate representation of males with TEST-deficient MetS.…”

Combination of low-dose testosterone and vildagliptin confers cardioprotection in castrated obese rats

“…Donner and colleagues reported that the rats fed with the obesogenic diet for 28 weeks had a similar level of serum testosterone level as the control rats (Donner et al 2015), whereas Silva and colleagues reported that HFD feeding for 30 weeks effectively reduced plasma testosterone levels in obese rats, compared with lean rats (Silva et al 2015). Our data indicated that testosterone deprivation did not affect peripheral insulin-resistant status, but it led to a reduction in both body weight and visceral fat weight.…”

Testosterone Deprivation Aggravates Left-Ventricular Dysfunction in Male Obese Insulin-Resistant Rats via Impairing Cardiac Mitochondrial Function and Dynamics Proteins

“…Our previous study using obese insulin-resistant rats demonstrated that testosterone deprivation at a very young age followed by long-term consumption of a high-fat diet (HFD) could accelerate but not aggravate LV dysfunction [4]. A recent study showed that obese insulin-resistant rats subjected to testos terone deprivation in middle age had an exacerbated insulin-resistant condition as indicated by increased HOMA-IR [12]. In addition, LV mass was also reduced and serum CK-MB levels were increased in testosterone-deprived obese insulin-resistant rats subjected to myocardial ischemia reperfusion injury [13].…”