Repercussões metabólicas induzidas pela privação hídrica em camundongos e o papel da sinalização ocitocinérgica na manutenção da massa muscular

Abstract

Dehydration is referred as a deficit in total body water, consequently to inadequate acute and/or chronic fluid intake. It is, therefore, a challenge to hydroelectrolytic homeostasis. It is currently known that inadequate hydration seems to predispose many chronic diseases, and also loss of muscle function, as well as predisposing to sarcopenia, the loss of muscle mass associated with aging. Besides, dehydration contributes to a series of metabolic and hydroelectrolytic arrangements, recruited as compensatory mechanisms to compensate osmotic stress. Nevertheless, little is known about the precise molecular mechanisms involved in systemic and muscle metabolism adaptation to dehydration. Therefore, the present project (registered as nº 4492070222) aimed to evaluate the metabolic consequences of a 36 h water deprivation protocol in C57BL/6 male mice. It was seen that dehydration resulted in loss of body mass, hyporexia and hypernatremia, but with no alteration in the haematocrit. These findings were accompanied by hypoglycaemia, hypercholesterolemia, increased activity of vasopressinergic and oxytocinergic neurons in the supraoptic and paraventricular hypothalamic nuclei and a reduction in respiratory exchange ratio at the last nocturnal period observed, suggesting lesser carbohydrate recruitment as energy source. Curiously, loss of body mass was not accompanied by muscle mass loss in soleus but increased extensor digitorum longus (EDL) mass, suggesting an adaptation or resistance mechanism to dehydration. Despite absence of mass loss, soleus muscle suffered a reduction in the activity of Akt-dependent signalling pathway, accompanied by increased total and proteasomal proteolysis, which were independent of MuRF-1, p62 e LC3. Moreover, oxytocinergic signaling, despite being essential to a dehydrated state, does not seem to contribute to muscle mass maintenance, since the expression of its receptor and the activity of protein kinase C remained unchanged. Hence, this research enlightens the procatabolic potential of dehydration, associated with loss of both muscle protein content and systemic energy stores, compromising energy metabolism homeostasis.