Dataset Information

Endospanin1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling.

ABSTRACT: The hypothalamic arcuate nucleus (ARC) is a major integration center for energy and glucose homeostasis that responds to leptin. Resistance to leptin in the ARC is an important component of the development of obesity and type 2 diabetes. Recently, we showed that Endospanin1 (Endo1) is a negative regulator of the leptin receptor (OBR) that interacts with OBR and retains the receptor inside the cell, leading to a decreased activation of the anorectic STAT3 pathway. Endo1 is up-regulated in the ARC of high fat diet (HFD)-fed mice, and its silencing in the ARC of lean and obese mice prevents and reverses the development of obesity.

Objective

Herein we investigated whether decreased Endo1 expression in the hypothalamic ARC, associated with reduced obesity, could also ameliorate glucose homeostasis accordingly.

Methods

We studied glucose homeostasis in lean or obese mice silenced for Endo1 in the ARC via stereotactic injection of shRNA-expressing lentiviral vectors.

Results

We observed that despite being leaner, Endo1-silenced mice showed impaired glucose homeostasis on HFD. Mechanistically, we show that Endo1 interacts with p85, the regulatory subunit of PI3K, and mediates leptin-induced PI3K activation.

Conclusions

Our results thus define Endo1 as an important hypothalamic integrator of leptin signaling, and its silencing differentially regulates the OBR-dependent functions.

SUBMITTER: Vauthier V

PROVIDER: S-EPMC5220283 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature

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Publications

Endospanin1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling.

Vauthier Virginie V Roujeau Clara C Chen Patty P Sarkis Chamsy C Migrenne Stéphanie S Hosoi Toru T Ozawa Koichiro K Rouillé Yves Y Foretz Marc M Mallet Jacques J Launay Jean-Marie JM Magnan Christophe C Jockers Ralf R Dam Julie J

Molecular metabolism 20161103 1

The hypothalamic arcuate nucleus (ARC) is a major integration center for energy and glucose homeostasis that responds to leptin. Resistance to leptin in the ARC is an important component of the development of obesity and type 2 diabetes. Recently, we showed that Endospanin1 (Endo1) is a negative regulator of the leptin receptor (OBR) that interacts with OBR and retains the receptor inside the cell, leading to a decreased activation of the anorectic STAT3 pathway. Endo1 is up-regulated in the ARC ...[more]

PMID: 28123946

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Project description:BackgroundObesity is defined as abnormal or excessive fat accumulation, provoking many different diseases, such as obesity and type 2 diabetes. Type 2 diabetes is a chronic-degenerative disease characterized by increased blood glucose levels. Obesity and type 2 diabetes are currently considered public health problems, and their prevalence has increased over the last few years. Because of the high cost involved in the treatment of both diseases, different alternatives have been sought. However, the general population uses medicinal plants, in the form of tea or infusions, to treat different diseases. Therefore, traditional medicine using medicinal plants has been investigated as a possible treatment for type 2 diabetes and body weight control.Aim of the studyThe purpose of this review is to find medicinal plants used in Mexico that could exert their beneficial effect by regulating insulin secretion and body weight control.Material and methodFor the development of this review, Mexican plants used in traditional medicine to treat type 2 diabetes and body weight control were searched in PubMed, Google Scholar, and Scopus. The inclusion criteria include plants that presented a significant reduction in blood glucose levels and/or an increase in insulin secretion.ResultsWe found 306 Mexican plants with hypoglycemic effects. However, plants that did not show evidence of an increase in insulin secretion were eliminated. Finally, only five plants were included in this review: Momordica charantia L. (melón amargo), Cucurbita ficifolia bouché (chilacayote), Coriandrum sativum L. (cilantro), Persea americana Mill. (aguacate) Bidens pilosa (amor seco), including 39 articles in total. Here, we summarized the plant extracts (aqueous and organic) that have previously been reported to present hypoglycemic effects, body weight control, increased secretion and sensitivity of insulin, improvement of pancreatic β cells, and glucose tolerance. Additionally, these effects may be due to different bioactive compounds present in the plants' extracts.ConclusionBoth in vivo and in vitro studies are required to understand the mechanism of action of these plant extracts regarding insulin secretion to be used as a possible treatment for type 2 diabetes and body weight control in the future.

Dataset Information

Endospanin1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling.

Objective

Methods

Results

Conclusions

Publications

Endospanin1 affects oppositely body weight regulation and glucose homeostasis by differentially regulating central leptin signaling.

Similar Datasets

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