ENHANCED FOOD INTAKE SUPPRESSION AND BODY MASS REDUCTION WITH COMBINED L-NAME AND LEPTIN ADMINISTRATION IN FASTED RATS
DOI:
https://doi.org/10.15547/tjs.2024.03.002Keywords:
nitric oxide, L-NAME, leptin, food intake, body mass, body temperature, feverAbstract
PURPOSE: This study aimed to investigate the effect of combining Nω-Nitro-L-arginine methyl ester (L-NAME) and leptin on food intake and body mass gain in fasted rats, as both have been shown to suppress food consumption. Additionally, the study evaluated the impact of L-NAME on fever induced by leptin.
METHODS: L-NAME and recombinant rat leptin were administered intraperitoneally, both alone and in combination, to fasted rats. Measurements included monitoring body temperature via rectal thermocouple probes, and assessing food intake and body mass gain 24 hours post-injection.
RESULTS: Systemic administration of L-NAME (50 mg/kg, i.p.) abolished the febrile response elicited by leptin. Furthermore, administering leptin (0.5 mg/kg, i.p.) and L-NAME (50 mg/kg, i.p.), alone or in combination, suppressed food intake and body mass gain in fasted rats after a 24-hour period. Notably, combining leptin and L-NAME had a more pronounced effect on food intake suppression and body mass loss than using either drug alone.
CONCLUSIONS: It could be speculated that the combination of leptin and L-NAME might potentially serve as an effective treatment for obesity, given their enhanced effects on food intake suppression and body mass loss observed in the study. Additionally, these results suggest a clear involvement of nitric oxide synthase during leptin-induced fever.
References
Branco LG, Soriano RN, Steiner AA. Gaseous mediators in temperature regulation. Compr Physiol., 4(4):1301-1338, 2014.
Morley JE, Farr SA, Sell RL, et al. Nitric oxide is a central component in neuropeptide regulation of appetite. Peptides, 32(4):776-780, 2011.
Nisoli E, Clementi E, Paolucci C, et al. Mitochondrial biogenesis in mammals: the role of endogenous nitric oxide. Science, 299(5608):896-899, 2003.
Patel B, New LE, Griffiths JC, et al. Inhibition of mitochondrial fission and iNOS in the dorsal vagal complex protects from overeating and weight gain. Mol Metab., 43:101123, 2021.
Kozak W, Kozak A. Genetic Models in Applied Physiology. Differential role of nitric oxide synthase isoforms in fever of different etiologies: studies using Nos gene-deficient mice. J Appl Physiol., 94(6):2534-2544, 2003.
Pan WW, Myers MG Jr. Leptin and the maintenance of elevated body weight. Nat Rev Neurosci., 19(2):95-105, 2018.
Hristov M, Landzhov B, Nikolov R, et al. Central, but not systemic, thermoregulatory effects of leptin are impaired in rats with obesity: interactions with GABAB agonist and antagonist. Amino Acids, 51(7):1055-1063, 2019.
Sachot C, Poole S, Luheshi GN. Circulating leptin mediates lipopolysaccharide-induced anorexia and fever in rats. J Physiol., 561(Pt 1):263-272, 2004.
Luheshi GN, Gardner JD, Rushforth DA, et al. Leptin actions on food intake and body temperature are mediated by IL-1. Proc Natl Acad Sci U S A, 96(12):7047-7052, 1999.
Hristov M, Landzhov B, Yakimova K. Increased NADPH-diaphorase reactivity in the hypothalamic paraventricular nucleus and tanycytes following systemic administration of leptin in rats. Acta Histochem., 121(6):690-694, 2019.
Hristov M, Landzhov B, Yakimova K. Cafeteria diet-induced obesity reduces leptin-stimulated NADPH-diaphorase reactivity in the hypothalamic arcuate nucleus of rats. Acta Histochem., 122(7):151616, 2020.
Rodríguez A, Becerril S, Méndez-Giménez L, et al. Leptin administration activates irisin-induced myogenesis via nitric oxide-dependent mechanisms, but reduces its effect on subcutaneous fat browning in mice. Int J Obes, 39(3):397-407, 2015.
Bełtowski J. Leptin and the regulation of endothelial function in physiological and pathological conditions. Clin Exp Pharmacol Physiol, 39(2):168-178, 2012.
Ayers NA, Kapás L, Krueger JM. The inhibitory effects of N omega-nitro-L-arginine methyl ester on nitric oxide synthase activity vary among brain regions in vivo but not in vitro. Neurochem Res, 22(1):81-86, 1997.
Morley JE, Flood JF. Competitive antagonism of nitric oxide synthetase causes weight loss in mice. Life Sci, 51(16):1285-1289, 1992.
Sadler CJ, Wilding JP. Reduced ventromedial hypothalamic neuronal nitric oxide synthase and increased sensitivity to NOS inhibition in dietary obese rats: further evidence of a role for nitric oxide in the regulation of energy balance. Brain Res, 1016(2):222-228, 2004.
Kamerman P, Mitchell D, Laburn H. Circadian variation in the effects of nitric oxide synthase inhibitors on body temperature, feeding and activity in rats. Pflugers Arch, 443(4):609-616, 2002.
Hristov M, Lazarov L. Inhibition of nitric oxide synthase or cystathionine gamma-lyase abolishes leptin-induced fever in male rats. J Therm Biol, 112:103443, 2023.
Idrizaj E, Traini C, Vannucchi MG, et al. Nitric Oxide: From Gastric Motility to Gastric Dysmotility. Int J Mol Sci, 22(18):9990, 2021.
Verschueren S, Janssen P, Van Oudenhove L, et al. Effect of pancreatic polypeptide on gastric accommodation and gastric emptying in conscious rats. Am J Physiol Gastrointest Liver Physiol, 307(1):G122-G128, 2014.
Dick JM, Lefebvre RA. Influence of different classes of NO synthase inhibitors in the pig gastric fundus. Naunyn Schmiedebergs Arch Pharmacol, 356(4):488-494, 1997.
Tack J, Demedts I, Meulemans A, et al. Role of nitric oxide in the gastric accommodation reflex and in meal induced satiety in humans. Gut, 51(2):219-224, 2002.
Obradovic M, Sudar-Milovanovic E, Soskic S, et al. Leptin and Obesity: Role and Clinical Implication. Front Endocrinol, 12:585887, 2021.
Park SJ, Yu Y, Zides CG, et al. Mechanisms of reduced leptin-mediated satiety signaling during obesity. Int J Obes, 46(6):1212-1221, 2022.
Benamar K, Xin L, Geller EB, et al. Effect of central and peripheral administration of a nitric oxide synthase inhibitor on morphine hyperthermia in rats. Brain Res, 894(2):266-273, 2001.
Nunan BLCZ, Drummond LR, Rodrigues QT, et al. Inhibition of nNOS in the paraventricular nucleus of hypothalamus decreases exercise-induced hyperthermia. Brain Res Bull, 177:64-72, 2021.
Maskrey M, Megirian D, Farkas GA. Effect of changing body temperature on the ventilatory and metabolic responses of lean and obese Zucker rats. Am J Physiol., 275(2):R531-R540, 1998.
Rosenthal M, Roth J, Störr B, et al. Fever response in lean (Fa/-) and obese (fa/fa) Zucker rats and its lack to repeated injections of LPS. Physiol Behav, 59(4-5):787-793, 1996.
Nakano H, Lee SD, Ray AD, et al. Role of nitric oxide in thermoregulation and hypoxic ventilatory response in obese Zucker rats. Am J Respir Crit Care Med, 164(3):437-442, 2001.
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