University of Pécs
Institute for Translational Medicine
Address: 12 Szigeti str. H-7624 Pécs, Hungary
From the point of view of energy homeostasis, aging is characterized first by an increase in body weight and fat mass (middle-aged obesity), then, in old age-groups by a drop in body weight and sarcopenia. Both obesity epidemic and aging anorexia causing weight loss of old people in the Western world present severe public health burden on our society. Neuropeptides may play a role in the central regulatory mechanisms of these processes. Our animal research focuses on these mechanisms. To distinguish between the effects of aging and those of body composition, we carry out the experiments in calorie-restricted and also in diet-induced obese animals. The perinatal period is known to be critically important in the development of appetite regulating centers involving neuropeptides of hypothalamus-adipose tissue axis and the gut–brain communication. Our complex analysis of the effects of different peptides on a wide range of parameters of energy balance aims to clarify: How do the energy balance and the most important regulatory neuropeptides change during the course of life in perinatally overfed/underfed offsprings? We assume, that maternal high fat diet and obesity accelerate those age-dependent biphasic changes in neuropeptidergic regulation of body weight, which may promote an earlier onset of both middle-aged obesity and aging anorexia leading to sarcopenia.
The exploration of these long-term mechanisms will lead to implementation of interventional strategies and improved translation of proposed interventional therapies (nutritional corrections during pregnancy or in the early neonatal period to reverse an inadequate programming) before they can be implemented in humans. That will have beneficial implications in breaking a programmed transgenerational cycle of metabolic disorders. In order to identify new therapeutic targets of obesity, we test novel peptide mediators with potential roles in the regulation of energy balance and the effects of inranasal application of the peptides (a clinically viable mode of delivery).
We study the effects of intracerebroventricular injections or infusions of agonists or antagonists of anabolic and catabolic mediator systems in rodents of different age-groups and nutritional states: 1) on the metabolic rate (oxygen consumption), core temperature and heat loss in metabolic chambers (indirect calorimetry; 2) on the circadian rhythm of core temperature, heart rate (parameter indicating metabolic rate), physical activity and feeding behavior in a biotelemetric system (MiniMitter); 3) on the spontaneous or fasting-induced food intake and corresponding body weight changes in an automated FeedScale system. We study the changes in body composition in relation to the age and to the infusion treatments. In order to reveal long-term influence of perinatal nutrition, we perform an analysis of long-term energy balance in adult Wistar rats born to high-fat diet-fed or calorie-restricted dams. In addition, we investigate the effects of inranasal application of certain peptides. Besides this complex in vivo analysis of energy metabolism, we apply in vitro analysis of the regulation of the hypothalamic peptide systems.
Füredi N, Mikó A, Gaszner B, Feller D, Rostás I, Tenk J, Solymár M, Balaskó M, Pétervári E.: Activity of the hypothalamic melanocortin system decreases in middle-aged and increases in old rats. (2018) J Gerontol A Biol Sci Med Sci. 73(4):438-445.
Tékus É, Mikó A, Füredi N, Rostás I, Tenk J, Kiss T, Szitter I, Balaskó M, Helyes Z, Wilhelm M, Pétervári E.: Body fat of rats of different age-groups and nutritional states: assessment by micro-CT and skinfold thickness. (2018) J Appl Physiol 124(2):268-275.
Mikó A, Füredi N, Tenk J, Rostás I, Soós S, Solymár M, Székely M, Balaskó M, Brunner SM, Kofler B, Pétervári E. : Acute central effects of alarin on the regulation on energy homeostasis. (2017) Neuropeptides. 64:117-122.
Pétervári E., Rostás I., Soós S., Tenk J., Mikó A., Füredi N., Székely M., Balaskó M.: Age versus nutritional state in the development of central leptin resistance. Peptides 56C: 59-67 (2014)
Balaskó M., Rostás I., Füredi N., Mikó A., Tenk J., Cseplő P., Koncsecskó-Gáspár M., Soós Sz., Székely M., Pétervári E.: Age and nutritional state influence the effects of cholecystokinin on energy balance. (2013) Exp. Gerontol. 48 (11): 1180-1188.
Pétervári E., Szabad A.O., Soós S., Garami A., Székely M., Balaskó M.: Central alpha-MSH infusion in rats: Disparate anorexic vs. metabolic changes with aging. (2011) Regul. Pept. 166 (1-3): 105-111.
Pétervári E., Soós S., Székely M., Balaskó M.: Alterations in the peptidergic regulation of energy balance in the course of aging. (2011) Curr. Protein Pept. Sci. 12(4): 316-324