Swimming exercise at weaning improves glycemic control and inhibits the onset of monosodium L-glutamate-obesity in mice A E Andreazzi, D X Scomparin, F P Mesquita, S L Balbo 1 , C Gravena, J C De Oliveira, W Rinaldi, R M G Garcia 2 , S Grassiolli and P C F Mathias Laboratory of Secretion Cell Biology, Department of Cell Biology and Genetics, State University of Maringa ´, Avenida Colombo 5790, Bloco H-67, S/019, 87020-900 Maringa ´, PR, Brazil 1 Laboratory of Physiology, State University of Western Parana ´, 85819-110, Cascavel, PR, Brazil 2 Laboratoryof Cell Biology, Department of Biology, Federal University of Juiz de Fora, 36036-900, Juiz de Fora, MG, Brazil (Correspondence should be addressed to P C F Mathias; Email: pmathias@uem.br) Abstract Swimming exercises by weaning pups inhibited hypothalamic obesity onset and recovered sympathoadrenal axis activity, but this was not observed when exercise training was applied to young adult mice. However, the mechanisms producing this improved metabolism are still not fully understood. Low-intensity swimming training started at an early age and was undertaken to observe glycemic control in hypothalamic–obese mice produced by neonatal treatment with monosodium L-glutamate (MSG). Whereas MSG and control mice swam for 15min/day, 3 days a week, from the weaning stage up to 90 days old, sedentary MSG and normal mice did not exercise at all. After 14 h of fasting, animals were killed at 90 days of age. Perigonadal fat accumulation was measured to estimate obesity. Fasting blood glucose and insulin concentrations were also measured. Fresh isolated pancreatic islets were used to test glucose-induced insulin release and total catecholamine from the adrenal glands was measured. Mice were also submitted to intraperitoneal glucose tolerance test. MSG-obese mice showed fasting hyperglycemia, hyperinsulinemia, and glucose intolerance. Severe reduction of adrenal catecholamines content has also been reported. Besides, the inhibition of fat tissue accretion, exercise caused normalization of insulin blood levels and glycemic control. The pancreatic islets of obese mice, with impaired glucose-induced insulin secretion, were recovered after swimming exercises. Adrenal catecholamine content was increased by swimming. Results show that attenuation of MSG-hypothalamic obesity onset is caused, at least in part, by modulation of sympathoadrenal axis activity imposed by early exercise, which may be associated with subsequent glucose metabolism improvement. Journal of Endocrinology (2009) 201, 351–359 Introduction Metabolic syndrome increases as obesity becomes a world- wide phenomenon, putting public health authorities on alert. Although a number of different sets of diagnostic criteria have been proposed for this syndrome, it is generally agreed that insulin resistance, hyperglycemia, dyslipidemia, hypertension, and obesity are its five key features (Shaw et al. 2005). The present pandemic is even more serious due to an increase in child metabolic syndrome. Young people may be obese and overweight and even present insulin resistance, hyper- insulinemia, hypertension, and hypercholinesteronemia. Moreover, some even develop non-insulin dependent diabetes mellitus (Weiss & Caprio 2005). Epidemiologic findings indicate that there is a direct correlation between obesity in childhood and metabolic syndrome onset in adult life (Henriksen et al. 1998). Although mechanisms that cause obesity, including early obesity onset, are still obscure, it has been reported that, in obese human beings and experimental animals, metabolic dysfunction may be diagnosed by the deterioration of pancreatic b-cell functions (Prentki & Nolan 2006). b-cell functions are impaired and glucose-induced insulin release is enhanced in obesity, which contributes to hyperinsulinemia (Grassiolli et al. 2007). Peripheral insulin resistance in obesity demands an extreme effort of b-cells to produce and release increasing amounts of insulin, which still does not decrease high blood glucose concentration. However, without any improvement in insulin resistance and decreased hyperglycemia, b-cells lose their capacity to regulate insulin secretion and leave high blood glucose levels uncontrolled. Similar to glucose, other nutrients, such as amino-acids, fatty acids, and their metabolites, also stimulate insulin secretion by pancreatic b-cells. These secretagogues induce an increase in cell metabolism and subsequent ATP production. Potassium ATP sensitive channels (K ATP ) are inactivated by an increase in ATP/ADP ratio. Membrane depolarization and subsequently the activation of voltage 351 Journal of Endocrinology (2009) 201, 351–359 DOI: 10.1677/JOE-08-0312 0022–0795/09/0201–351 q 2009 Society for Endocrinology Printed in Great Britain Online version via http://www.endocrinology-journals.org Downloaded from Bioscientifica.com at 05/23/2020 03:02:27PM via free access