title: Mitochondrial and metabolic dysfunction in renal convoluted tubules of obese mice: protective role of melatonin.
abstract: Obesity is a common and complex health problem, which impacts crucial organs; it is also considered an independent risk factor for chronic kidney disease. Few studies have analyzed the consequence of obesity in the renal proximal convoluted tubules, which are the major tubules involved in reabsorptive processes. For optimal performance of the kidney, energy is primarily provided by mitochondria. Melatonin, an indoleamine and antioxidant, has been identified in mitochondria, and there is considerable evidence regarding its essential role in the prevention of oxidative mitochondrial damage. In this study we evaluated the mechanism(s) of mitochondrial alterations in an animal model of obesity (ob/ob mice) and describe the beneficial effects of melatonin treatment on mitochondrial morphology and dynamics as influenced by mitofusin-2 and the intrinsic apoptotic cascade. Melatonin dissolved in 1% ethanol was added to the drinking water from postnatal week 5-13; the calculated dose of melatonin intake was 100 mg/kg body weight/day. Compared to control mice, obesity-related morphological alterations were apparent in the proximal tubules which contained round mitochondria with irregular, short cristae and cells with elevated apoptotic index. Melatonin supplementation in obese mice changed mitochondria shape and cristae organization of proximal tubules, enhanced mitofusin-2 expression, which in turn modulated the progression of the mitochondria-driven intrinsic apoptotic pathway. These changes possibly aid in reducing renal failure. The melatonin-mediated changes indicate its potential protective use against renal morphological damage and dysfunction associated with obesity and metabolic disease.
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Stacchiotti
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Gaia
authors.initials: G
authors.lastname: Favero
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Lorena
authors.initials: L
authors.lastname: Giugno
authors.affiliation: Istituto Zooprofilattico Sperimentale della Lombardia ed Emilia Romagna, OIE Reference Laboratory for RHD, Brescia, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Lavazza
authors.affiliation: Department of Cellular and Structural Biology, UT Health Science Center San Antonio, San Antonio, Texas, United States of America.
authors.forename: Russel J
authors.initials: RJ
authors.lastname: Reiter
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Luigi Fabrizio
authors.initials: LF
authors.lastname: Rodella
authors.affiliation: Anatomy and Physiopathology Division, Department of Clinical and Experimental Sciences, University of Brescia, Brescia, Italy.
authors.forename: Rita
authors.initials: R
authors.lastname: Rezzani
mesh_terms: D000818:Animals; D017209:Apoptosis; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008550:Melatonin / Q000494:pharmacology* / Q000627:therapeutic use; D051379:Mice; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009765:Obesity / Q000150:complications / Q000378:metabolism*; D051437:Renal Insufficiency / Q000209:etiology / Q000517:prevention & control*
chemical_list: D020558:GTP Phosphohydrolases; C488751:Mfn2 protein, mouse; D008550:Melatonin