Leptin-deficient obese mice: a multi-organ stress model rescued by melatonin

Obesity is an epidemic health concern in Western countries that strongly involves social and sanitary costs and must be urgently fought. Different animal models of obesity are crucial in basic research to provide information on multifactorial pathogenic mechanisms and pathways useful to develop clinical guidelines. In this chapter we described, through the use of light and transmission electron microscopy, hepatic and renal changes induced in genetically obese (ob/ob) mice characterized by the ablation of leptin gene, a hypothalamic neuropeptide involved in the regulation of food intake and metabolic turnover. In detail, we characterized fibrosis, steatosis, inflammation, and obviously mitochondrial and endoplasmic reticulum stress in ob/ob and B6.V-(lean)/Ola Hsd mice as lean control group. Histopathological (haematoxylin eosin and Azur II-Methylene blue stainings), immunohistochemical (anti-SREBP1, anti-GRP78, antiCHOP) and ultrastructural analysis greatly indicate that liver, in genetically induced obese mice, is more oriented on macrosteatosis, whereas in the kidney mitochondrial fission is evident. Melatonin intake in drinking water for 8 weeks significantly reduced steatosis, endoplasmic reticulum stress and mitochondrial alterations in ob/ob mice at the level of these two crucial organs for the pathogenic process of obesity. These microscopic findings suggested that melatonin intake may be an effective dietary addition to mitigate obesity.