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| Author(s): |
João Alfredo Bolivar Pedroso
Total Authors: 1
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| Document type: | Doctoral Thesis |
| Press: | São Paulo. |
| Institution: | Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) |
| Defense date: | 2016-11-21 |
| Examining board members: |
José Donato Júnior;
William Tadeu Lara Festuccia;
Marcelo Alves da Silva Mori;
Eduardo Rochete Ropelle;
Francemilson Goulart da Silva
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| Advisor: | José Donato Júnior |
| Abstract | |
The objective of this study was to investigate the effects of leptin sensitivity on food intake, energy balance and modulation of glycemic homeostasis. We produced mice lacking SOCS3 only in leptin receptor-expressing cells (LepR SOCS3 KO mice). Mice received high-fat diet to induce obesity. Inactivation of SOCS3 only in LepR-expressing cells protected against leptin resistance induced by diet-induced obesity (DIO), but did not prevent weight gain. However, LepR SOCS3 KO mice were protected from insulin resistance induced by DIO. Next, another group of animals were subjected to a 48 hours fasting, followed by refeeding. LepR SOCS3 KO mice showed attenuated food intake and weight regain after a 48 h fasting. Post-restriction hyperleptinemia was also prevented in LepR SOCS3 KO mice. Remarkably, LepR SOCS3 KO mice showed impaired glucose control during fasting, leading to hypoglycemia. To investigate the mechanisms of action, we showed that increased leptin sensibility modulates the sympathetic nervous system and can be harmful to glucose homeostasis during fasting. In conclusion, our results help to understand the effects of leptin to prevent obesity, but also highlight possible side effects from strategies that increase leptin sensitivity. (AU) | |
| FAPESP's process: | 13/25032-2 - The role of SOCS3 in the control of hyperphagia, body weight regain and gluconeogenesis after a period of food restriction |
| Grantee: | João Alfredo Bolivar Pedroso |
| Support Opportunities: | Scholarships in Brazil - Doctorate |