leptin and Ciliopathies
leptin has been researched along with Ciliopathies* in 2 studies
Reviews
1 review(s) available for leptin and Ciliopathies
Article | Year |
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Cilia signaling and obesity.
An emerging number of rare genetic disorders termed ciliopathies are associated with pediatric obesity. It is becoming clear that the mechanisms associated with cilia dysfunction and obesity in these syndromes are complex. In addition to ciliopathic syndromic forms of obesity, several cilia-associated signaling gene mutations also lead to morbid obesity. While cilia have critical and diverse functions in energy homeostasis including their roles in centrally mediated food intake as well as in peripheral tissues, many questions remain. Here, we briefly discuss the syndromic ciliopathies and monoallelic cilia signaling gene mutations associated with obesity. We also describe potential ways cilia may be involved in common obesity. We discuss how neuronal cilia impact food intake potentially through leptin signaling and changes in ciliary G protein-coupled receptor (GPCR) signaling. We highlight several recent studies that have implicated the potential for cilia in peripheral tissues such as adipose and the pancreas to contribute to metabolic dysfunction. Then we discuss the potential for cilia to impact energy homeostasis through their roles in both development and adult tissue homeostasis. The studies discussed in this review highlight how a comprehensive understanding of the requirement of cilia for the regulation of diverse biological functions will contribute to our understanding of common forms of obesity. Topics: Adaptor Proteins, Signal Transducing; Adipose Tissue; Adult; Alpha-Ketoglutarate-Dependent Dioxygenase FTO; Animals; Child; Cilia; Ciliopathies; Eating; Gene Expression Regulation; Humans; Hypothalamus; Leptin; Neurons; Obesity, Morbid; Pancreas; Pediatric Obesity; Signal Transduction | 2021 |
Other Studies
1 other study(ies) available for leptin and Ciliopathies
Article | Year |
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MetAP2 inhibition reduces food intake and body weight in a ciliopathy mouse model of obesity.
The ciliopathies Bardet-Biedl syndrome and Alström syndrome are genetically inherited pleiotropic disorders with hyperphagia and obesity as primary clinical features. Methionine aminopeptidase 2 inhibitors (MetAP2i) have been shown in preclinical and clinical studies to reduce food intake, body weight, and adiposity. Here, we investigated the effects of MetAP2i administration in a mouse model of ciliopathy produced by conditional deletion of the Thm1 gene in adulthood. Thm1 conditional knockout (cko) mice showed decreased hypothalamic proopiomelanocortin expression as well as hyperphagia, obesity, metabolic disease, and hepatic steatosis. In obese Thm1-cko mice, 2-week administration of MetAP2i reduced daily food intake and reduced body weight 17.1% from baseline (vs. 5% reduction for vehicle). This was accompanied by decreased levels of blood glucose, insulin, and leptin. Further, MetAP2i reduced gonadal adipose depots and adipocyte size and improved liver morphology. This is the first report to our knowledge of MetAP2i reducing hyperphagia and body weight and ameliorating metabolic indices in a mouse model of ciliopathy. These results support further investigation of MetAP2 inhibition as a potential therapeutic strategy for ciliary-mediated forms of obesity. Topics: Adaptor Proteins, Signal Transducing; Animals; Blood Glucose; Body Weight; Ciliopathies; Disease Models, Animal; Eating; Enzyme Inhibitors; Fatty Liver; Leptin; Liver; Male; Methionyl Aminopeptidases; Mice; Mice, Inbred C57BL; Mice, Knockout; Mice, Obese; Obesity; Transcriptome | 2020 |