Consequences of neonatal Diabetes Mellitus to pubertal adipose tissue development in male rats. 1. Effects on adipogenesis. 2. Effects of thiazolidinedione and melatonin treatment

Abstract

Adipose tissue, nowadays considered an endocrine and metabolic organ, participates actively in the regulation of the energy metabolism and store, of feeding behavior and body weight. Deficiencies in its formation compromises the body development and quality of life as seen in lipodystrophic syndromes, leading to severe metabolic alterations like insulin resistance, diabetes mellitus and shortening of life expectancy. In the other extreme, obesity also produces similar metabolic abnormalities. For these reasons the understanding of the adipose tissue physiology is mandatory. The pubertal period shows an interesting characteristic regarding the adipose tissue: at this time, an important surge in the adipose mass development and in its capacity to produce adipokines occurs, particularly, leptin which, as is well-known, acts on maturation of the reproducing system in hypothalamus where the production of kisspeptins are stimulated that act on GnRH-producing neurons awakening the hypothalamic-pituitary-gonadal (HPG) axis. Diabetes Mellitus (DM), induced by massive destruction of b-cells, evolves with intense hyperglycemia, glicosúria, polyuria, polidipsia, polyphagia, tendency to keto-acidosis and weight loss. Its appearance before puberty, by compromising the adipose tissue development, disrupts the metabolic control, alters feeding behavior and maturation of hypothalamic endocrine axes, among which the HPG. Besides, these diabetic animals develop insulin resistance. Recently, we described in diabetic animals an important pineal gland insufficiency. As the deficient melatonin production also induces insulin resistance, this effect can aggravate the diabetic picture.In this study, by inducing DM in the neonatal period, we will evaluate its repercussions to the adipose tissue development throughout the puberty and to the metabolic, endocrine and gonadal control. As at this period, there is a great surge of adipogenesis, a systematic assessment of this phenomenon will be persecuted. In parallel, by the supplementation with melatonin trial, the effects of this treatment on the metabolic evolution of the diabetic picture and the adipose tissue response will be investigated. (AU)