Epiregulin induces leptin secretion and energy expenditure in high-fat diet-fed mice
| Autor: | Ouliana Ziouzenkova, David DiSilvestro, Rumana Yasmeen, Andrei Maiseyeu, Paolo Fadda, Kefeng Yang, Naresh C. Bal, Lu Xu, Muthu Periasamy, Qiwen Shen, Jacob H. Leung, Devan Kowdley, Aejin Lee |
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| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Leptin Male medicine.medical_specialty Endocrinology Diabetes and Metabolism medicine.medical_treatment Adipose Tissue White Adipokine White adipose tissue Intra-Abdominal Fat Diet High-Fat Epiregulin Article Cachexia 03 medical and health sciences Mice 0302 clinical medicine Endocrinology Internal medicine medicine Animals Secretion Obesity Chemistry Insulin digestive oral and skin physiology medicine.disease 030104 developmental biology Female Energy Metabolism Thermogenesis 030217 neurology & neurosurgery hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of endocrinology. 239(3) |
| ISSN: | 1479-6805 |
| Popis: | Adipokine leptin regulates neuroendocrine circuits that control energy expenditure, thermogenesis and weight loss. However, canonic regulators of leptin secretion, such as insulin and malonyl CoA, do not support these processes. We hypothesize that epiregulin (EREG), a growth factor that is secreted from fibroblasts under thermogenic and cachexia conditions, induces leptin secretion associated with energy dissipation. The effects of EREG on leptin secretion were studied ex vivo, in the intra-abdominal white adipose tissue (iAb WAT) explants, as well as in vivo, in WT mice with diet-induced obesity (DIO) and in ob/ob mice. These mice were pair fed a high-fat diet and treated with intraperitoneal injections of EREG. EREG increased leptin production and secretion in a dose-dependent manner in iAb fat explants via the EGFR/MAPK pathway. After 2 weeks, the plasma leptin concentration was increased by 215% in the EREG-treated group compared to the control DIO group. EREG-treated DIO mice had an increased metabolic rate and core temperature during the active dark cycle and displayed cold-induced thermogenesis. EREG treatment reduced iAb fat mass, the major site of leptin protein production and secretion, but did not reduce the mass of the other fat depots. In the iAb fat, expression of genes supporting mitochondrial oxidation and thermogenesis was increased in EREG-treated mice vs control DIO mice. All metabolic and gene regulation effects of EREG treatment were abolished in leptin-deficient ob/ob mice. Our data revealed a new role of EREG in induction of leptin secretion leading to the energy expenditure state. EREG could be a potential target protein to regulate hypo- and hyperleptinemia, underlying metabolic and immune diseases. |
| Databáze: | OpenAIRE |
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