Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesitya
| Autor: | Angela M. Ramos-Lobo, Daniella do Carmo Buonfiglio, Carol F. Elias, Lais I. Cardinali, João A.B. Pedroso, Isadora C. Furigo, Jose Donato, Julio Tirapegui |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
HFD high-fat diet SOCS3 suppressor of cytokine signaling-3 Leptin resistance NTS nucleus of the solitary tract Hypothalamus Type 2 diabetes Biology Insulin resistance POMC proopiomelanocortin VMH ventromedial nucleus of the hypothalamus Internal medicine Type 2 diabetes mellitus PKC protein kinase C medicine Glucose homeostasis SOCS3 Molecular Biology ITT insulin tolerance test Glucose tolerance test Suppressor of cytokine signaling-3 Leptin receptor KO knockout medicine.diagnostic_test Leptin PTPs protein-tyrosine phosphatases Insulin tolerance test digestive oral and skin physiology POMC ARH arcuate nucleus of the hypothalamus PI3K phosphatidylinositol 3-kinase Cell Biology DIO diet-induced obesity T2DM type 2 diabetes mellitus medicine.disease AP area postrema Endocrinology High-fat diet DMV dorsal motor nucleus of the vagus LepR leptin receptor GTT glucose tolerance test Original Article hormones hormone substitutes and hormone antagonists |
| Zdroj: | Molecular Metabolism |
| ISSN: | 2212-8778 |
| Popis: | Therapies that improve leptin sensitivity have potential as an alternative treatment approach against obesity and related comorbidities. We investigated the effects of Socs3 gene ablation in different mouse models to understand the role of SOCS3 in the regulation of leptin sensitivity, diet-induced obesity (DIO) and glucose homeostasis. Neuronal deletion of SOCS3 partially prevented DIO and improved glucose homeostasis. Inactivation of SOCS3 only in LepR-expressing cells protected against leptin resistance induced by HFD, but did not prevent DIO. However, inactivation of SOCS3 in LepR-expressing cells protected mice from diet-induced insulin resistance by increasing hypothalamic expression of Katp channel subunits and c-Fos expression in POMC neurons. In summary, the regulation of leptin signaling by SOCS3 orchestrates diet-induced changes on glycemic control. These findings help to understand the molecular mechanisms linking obesity and type 2 diabetes, and highlight the potential of SOCS3 inhibitors as a promising therapeutic approach for the treatment of diabetes. |
| Databáze: | OpenAIRE |
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