The effects of physical exercise about the glucose sensing in the hypothalamus of rats: the role of HIF2 alpha

Author(s)

Vagner Ramon Rodrigues Silva

• Document type: Doctoral Thesis
• Press: Limeira, SP.
• Institution: Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Aplicadas
• Defense date: 2018-03-19

Examining board members

Eduardo Rochete Ropelle; Adelino Sanchéz Ramos da Silva; Ellen Cristini de Freitas; Mario José Abdalla Saad; Licio Augusto Velloso

• Advisor: Eduardo Rochete Ropelle

Abstract

In mammals, food intake and energy expenditure are regulated by specific neurons located in the hypothalamus. The hypothalamus controls food intake and energy expenditure through hormonal and nutritional signals coming from the periphery. One of the major nutrients related to the control of food intake is glucose. Studies have shown that the selective loss of sensitivity glucose in hypothalamic neurons is related to overeating and obesity. Recently, Hypoxia Inducible Factor-2 (HIF2'alpha' protein) has emerged as an important regulator in the maintenance of glucose sensitivity and hypothalamic neurons. The loss of function of this molecule reduces the ability of neurons to detect the presence of glucose, resulting in increased food intake and body weight in mice. In this context, the maintenance of neuronal HIF2'alpha' functions can be considered a key strategy for maintaining lean phenotype. At the same time, the exercise is considered a major contributor to the control of body weight and energy expenditure. However, the effects of exercise on glucose sensitivity in the central nervous system (CNS) remain unexploited. Thus, the aim of this study is to investigate the effect of exercise on glucose sensitivity in the hypothalamus of rats and evaluate the expression of neuronal HIF2 'alpha'protein and the effect of lactate treatment about the neuronal HIF2'alpha' protein expression. First, Wistar rats were randomly separated into two groups: One group consumed standard chow diet (Chow), while the other group consumed high-fat diet for twelve weeks. Next, using the acute swimming protocol exercise for induction of lactatemia and after we did a treatment intracerebroventriculary (ICV) of glucose or lactate into the hypothalamus. Here, we showed that HFD consume caused obesity and loss neuronal glucose sensing when compared at control group. Acute physical exercises improved fasting glucose and food consumption and ameliorate the neuronal glucose sensing in obese rats. The HIF2'alpha' in the hypothalamus was raised and also serum and central lactate post-exercise in obese rats. Finally, the injection ICV of lactate increased content protein of HIF2'alpha' in the hypothalamus and reduced food intake in lean and obese rats. Taken together, our results suggest, at least in parts, that the HIF2'alpha' in the hypothalamus is mediate by lactate and the physical exercise can be a therapeutic target stimulating the lactatemia. In conclusion, hypothalamic HIF2'alpha' can be a target against obesity by improvement of neuronal glucose sensing (AU)

• FAPESP's process: 13/20052-5 - EFFECTS OF PHYSICAL EXERCISE ON THE SENSITIVITY OF GLUCOSE HYPOTHALAMUS IN RATS: ROLE OF PROTEIN ALPHA HIF2
• Grantee: Vagner Ramon Rodrigues Silva
• Support Opportunities: Scholarships in Brazil - Doctorate