Abstract
Inducing testosterone deficiency, as the standard treatment of prostate cancer, may cause metabolic disorders including insulin resistance, dyslipidemia, central obesity, cardiovascular diseases, and type 2 diabetes. This study measured responses to testosterone deficiency in high-carbohydrate, high-fat (H) diet-fed rats. We then tested whether eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) ethyl esters (Omacor) reversed these metabolic changes. Male Wistar rats (8–9 weeks old) were divided into eight groups with four groups fed corn starch and four groups fed H diet. For each diet, one group received diet only; one group was orchidectomized; one group was given leuprolide (gonadotrophin-releasing hormone agonist, 2 mg/kg every 4th week); and the last group was treated with leuprolide and their diet was supplemented with 3% Omacor for the last eight weeks. The protocol was for 16 weeks. Leuprolide worsened metabolic syndrome symptoms and cardiovascular function, and orchidectomy produced greater responses. In H fed leuprolide-treated rats, Omacor decreased systolic blood pressure and left ventricular diastolic stiffness, reduced infiltration of inflammatory cells and collagen deposition in the heart, and reduced lipid accumulation and inflammatory cell infiltration without improving liver damage. These results suggest that Omacor has potential to attenuate metabolic complications in prostate cancer patients with induced testosterone deprivation.
Highlights
Metabolic syndrome is the constellation of insulin resistance, impaired glucose tolerance, dyslipidemia, hypertension, and obesity that increases the risk for development of cardiovascular disease and type 2 diabetes, with an increasing prevalence in the last few decades [1]
High-carbohydrate, high-fat diet (H) did not alter plasma total testosterone concentrations compared to corn starch diet-fed rats (C)
CLOm: Rats treated with leuprolide for 16 weeks and fed corn starch diet for first 8 weeks followed by corn starch diet supplemented with 3% Omacor for the final 8 weeks
Summary
Metabolic syndrome is the constellation of insulin resistance, impaired glucose tolerance, dyslipidemia, hypertension, and obesity that increases the risk for development of cardiovascular disease and type 2 diabetes, with an increasing prevalence in the last few decades [1]. Low testosterone concentrations have been associated with many of these complications including insulin resistance, hyperinsulinemia, dyslipidemia, and cardiovascular disorders [3,4,5,6]. Mar. Drugs 2018, 16, 182 syndrome was associated with worse oncologic outcomes, in particular with more aggressive tumor features and biochemical recurrence [7,8]. GnRH agonists increase the risk of development of diabetes and cardiovascular disease, increase fat mass, and decrease lean mass [10,11,12]
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