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| Author(s): |
Laís Weissmann
Total Authors: 1
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| Document type: | Master's Dissertation |
| Press: | Campinas, SP. |
| Institution: | Universidade Estadual de Campinas (UNICAMP). Faculdade de Ciências Médicas |
| Defense date: | 2013-06-08 |
| Examining board members: |
Patrícia de Oliveira Prada;
Eduardo Rochete Ropelle;
Carla Roberta de Oliveira Carvalho
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| Advisor: | Patrícia de Oliveira Prada |
| Abstract | |
It was demonstrated that IkB kinase epsilon (IKK?) increased insulin resistance (IR) in liver and adipose tissue of diet-induced obesity (DIO) mice. The aims of this study are to investigate: 1) the expression and activation of IKK? in the hypothalamus from DIO mice and db/db, 2) the role of hypothalamic IKK? in the energy and glucose metabolism, and in insulin and leptin action/signaling. We observed increased expression and activation of IKK? in the hypothalamus from db/db and DIO mice compared with controls. Five days of intracerebroventricular (ICV) injections of CAY (pharmacological inhibitor of IKK?) or siRNA, via ICV mini-pump, reduced 80% of IKK? activity as well asthe phosphorylation of IRS1Ser307 and did not alter the phosphorylation of IKK?/? in hypothalamus from obese mice. Inhibition of IKK? (ICV) reduced fat mass, food intake and increased O2 consumption and expression of UCP-1 in the brown adipose tissue, improved anorexigenic effects of leptin and insulin, increased insulin receptor, AKT, JAK2 and STAT3 phosphorylation in the hypothalamus of DIO and db/db mice. These results persisted even if in pair-fed and pair-weight mice. Inhibition of IKK? with ICV CAY reduced: fasting glycemia, hepatic glucose production and the expression of PEPCK in liver of DIO and db/db animals. In summary, the data suggest that hypothalamic IKK? is activated in models of obesity and participates in the development of insulin and leptin resistance. Its inhibition reduces adiposity, food intake and increases energy expenditure. Hypothalamic IKK? influences the energy and glucose metabolism in obese mice. Thus, it can be suggested that the IKK? represents a link between obesity and insulin resistance in the hypothalamus and may be a new therapeutic target to treat insulin resistance, obesity and diabetes (AU) | |
| FAPESP's process: | 11/02289-2 - The role of IKK epsilon in hypothalamic nuclei in the regulation of energy balance in obese rodents |
| Grantee: | Laís Weissmann |
| Support Opportunities: | Scholarships in Brazil - Master |