Melatonin and diet-induced metabolic syndrome in rats: impact on the hypophysial-testicular axis

Abstract

Combinations of fructose- and fat-rich diets in experimental animals can model the human metabolic syndrome (MS). In rats, the increase in blood pressure (BP) after diet manipulation is sex related and highly dependent on testosterone secretion. However, the extent of the impact of diet on rodent hypophysial-testicular axis remains undefined. In the present study, rats drinking a 10% fructose solution or fed a high-fat (35%) diet for 10 weeks had higher plasma levels of luteinizing hormone (LH) and lower plasma levels of testosterone, without significant changes in circulating follicle-stimulating hormone or the weight of most reproductive organs. Diet manipulation brought about a significant increase in body weight, systolic BP, area under the curve (AUC) of glycemia after an intraperitoneal glucose tolerance test (IPGTT), and plasma low-density lipoprotein cholesterol, cholesterol, triglycerides, and uric acid levels. The concomitant administration of melatonin (25 μg/mL of drinking water) normalized the abnormally high LH levels but did not affect the inhibited testosterone secretion found in fructose- or high-fat-fed rats. Rather, melatonin per se inhibited testosterone secretion. Melatonin significantly blunted the body weight and systolic BP increase, the increase in the AUC of glycemia after an IPGTT, and the changes in circulating lipid profile and uric acid found in both MS models. The results are compatible with a primary inhibition of testicular function in diet-induced MS in rats and with the partial effectiveness of melatonin to counteract the metabolic but not the testicular sequelae of rodent MS.

Melatonin, mitochondria, and the metabolic syndrome

“…In rats fed from weaning with a high-fat diet melatonin decreased body weight gain, feed efficiency and plasma glucose, leptin and triglyceride levels [53] In middle-aged rats receiving a high caloric liquid diet, melatonin reduced weight gain and plasma insulin and leptin levels [54] In high-fat diet-fed mice, melatonin improved insulin sensitivity and glucose tolerance [55] In ovariectomized rats, melatonin was effective to reduce obesity [56][57][58] In olanzapine-treated rats, melatonin was effective to reduce obesity [59] In goldfish body weight gain and specific growth rate were reduced by melatonin treatment [60] Melatonin and its analog piromelatonin inhibited weight gain and improves insulin sensitivity in high-fat fed rats [52] In high-fat fed rats, melatonin attenuated body weight increase, the increase in plasma glucose, insulin, adiponectin, leptin, triglycerides and cholesterol levels, and counteracted disrupted 24 h patterns [61] Melatonin improves inflammation processes in liver and pancreas of senescence-accelerated prone male mice (SAMP8) [62,63] Melatonin reduced body weight gain, visceral adiposity, blood triglyceride and insulin levels and TBARS under a high calorie diet in rats. [64] In young male Zucker diabetic fatty rats melatonin treatment reduced mean weight gain without affecting food intake, decreased in a nonsignificant way blood pressure, and improved dyslipidemia [65] Melatonin improves MS induced by high fructose intake in rats without affecting food intake [66][67][68][69][70] Melatonin and its analog piromelatonin reduced blood pressure in spontaneously hypertensive rats [71] Melatonin prevents the development of the MS in male rats exposed to different light/dark regimens [72] Melatonin attenuates high fat diet-induced fatty liver disease in rats [73] Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats [74] Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats [75] Melatonin improves hyperglycemia, hypertriglyceridemia, polyphagia, and polydipsia in streptozotocin diabetic rats [76,…”

Inflammaging, Metabolic Syndrome and Melatonin: A Call for Treatment Studies

“…In rats fed from weaning with a high-fat diet melatonin decreased body weight gain, feed efficiency and plasma glucose, leptin and triglyceride levels [44] In middle-aged rats receiving a high caloric liquid diet, melatonin reduced weight gain and plasma insulin and leptin levels [45] In high-fat diet-fed mice, melatonin improved insulin sensitivity and glucose tolerance [46] In ovariectomized rats, melatonin was effective to reduce obesity [47][48][49] In olanzapine-treated rats, melatonin was effective to reduce obesity [50] In gold fish body weight gain and specific growth rate were reduced by melatonin treatment [51] Melatonin and its analog piromelatonin inhibited weight gain and improves insulin sensitivity in high-fat fed rats [52] In high-fat fed rats, melatonin attenuated body weight increase, the increase in plasma glucose, insulin, adiponectin, leptin, triglycerides and cholesterol levels, and counteracted disrupted 24 h patterns [53] Melatonin reduced body weight gain, visceral adiposity, blood triglyceride and insulin levels and TBARS under a high calorie diet in rats. [54] In young male Zucker diabetic fatty rats melatonin treatment reduced mean weight gain without affecting food intake, decreased in a non-significant way blood pressure, and improved dyslipidemia [55] Melatonin improves MS induced by high fructose intake in rats without affecting food intake [56][57][58][59] Melatonin and its analog piromelatonin reduced blood pressure in spontaneously hypertensive rats [60] Melatonin prevents the development of the MS in male rats exposed to different light/dark regimens [61] Melatonin attenuates high fat diet-induced fatty liver disease in rats [62] Melatonin, given at the time of reperfusion, prevents ventricular arrhythmias in isolated hearts from fructose-fed rats and spontaneously hypertensive rats [63] Melatonin ameliorates low-grade inflammation and oxidative stress in young Zucker diabetic fatty rats [64] Protective effects of melatonin against metabolic and reproductive disturbances in polycystic ovary syndrome in rats [65] Melatonin normalizes clinical and biochemical parameters of mild inflammation in diet-induced MS syndrome in rats [66] Melatonin counteracts changes in hypothalamic gene expression of signals regulating feeding behavior in high-fat fed rats…”