title: Melatonin improves insulin sensitivity independently of weight loss in old obese rats.
abstract: In aged rats, insulin signaling pathway (ISP) is impaired in tissues that play a pivotal role in glucose homeostasis, such as liver, skeletal muscle, and adipose tissue. Moreover, the aging process is also associated with obesity and reduction in melatonin synthesis from the pineal gland and other organs. The aim of the present work was to evaluate, in male old obese Wistar rats, the effect of melatonin supplementation in the ISP, analyzing the total protein amount and the phosphorylated status (immunoprecipitation and immunoblotting) of the insulin cascade components in the rat hypothalamus, liver, skeletal muscle, and periepididymal adipose tissue. Melatonin was administered in the drinking water for 8- and 12 wk during the night period. Food and water intake and fasting blood glucose remained unchanged. The insulin sensitivity presented a 2.1-fold increase both after 8- and 12 wk of melatonin supplementation. Animals supplemented with melatonin for 12 wk also presented a reduction in body mass. The acute insulin-induced phosphorylation of the analyzed ISP proteins increased 1.3- and 2.3-fold after 8- and 12 wk of melatonin supplementation. The total protein content of the insulin receptor (IR) and the IR substrates (IRS-1, 2) remained unchanged in all investigated tissues, except for the 2-fold increase in the total amount of IRS-1 in the periepididymal adipose tissue. Therefore, the known age-related melatonin synthesis reduction may also be involved in the development of insulin resistance and the adequate supplementation could be an important alternative for the prevention of insulin signaling impairment in aged organisms.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences-I, University of São Paulo USP, São Paulo, SP, Brazil.
authors.forename: Ricardo
authors.initials: R
authors.lastname: Zanuto
authors.forename: Mário A
authors.initials: MA
authors.lastname: Siqueira-Filho
authors.forename: Luciana C
authors.initials: LC
authors.lastname: Caperuto
authors.forename: Reury F P
authors.initials: RF
authors.lastname: Bacurau
authors.forename: Emiko
authors.initials: E
authors.lastname: Hirata
authors.forename: Rodrigo A
authors.initials: RA
authors.lastname: Peliciari-Garcia
authors.forename: Fernanda Gaspar
authors.initials: FG
authors.lastname: do Amaral
authors.forename: Anderson C
authors.initials: AC
authors.lastname: Marçal
authors.forename: Luciene M
authors.initials: LM
authors.lastname: Ribeiro
authors.forename: João P G
authors.initials: JP
authors.lastname: Camporez
authors.forename: Angelo Rafael
authors.initials: AR
authors.lastname: Carpinelli
authors.forename: Silvana
authors.initials: S
authors.lastname: Bordin
authors.forename: José
authors.initials: J
authors.lastname: Cipolla-Neto
authors.forename: Carla R O
authors.initials: CR
authors.lastname: Carvalho
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism / Q000627:therapeutic use*; D019587:Dietary Supplements; D004353:Drug Evaluation, Preclinical; D044882:Glucose Metabolism Disorders / Q000517:prevention & control; D007333:Insulin Resistance; D008297:Male; D008550:Melatonin / Q000378:metabolism / Q000627:therapeutic use*; D009765:Obesity / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000975:Antioxidants; D008550:Melatonin
keywords: aging; insulin; insulin signaling pathway; melatonin; obesity