1. Seipin Deficiency Leads to Energy Dyshomeostasis via Inducing Hypothalamic Neuroinflammation and Aberrant Expression of Neuropeptides.
- Author
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Cui W, Chen H, Lei L, Wang W, Lim KL, Zhang C, and Lu L
- Subjects
- Animals, Mice, Male, Neuroinflammatory Diseases etiology, Mice, Inbred C57BL, Hypoglycemic Agents pharmacology, Hypoglycemic Agents therapeutic use, Neuropeptides genetics, Neuropeptides deficiency, Gene Expression Regulation drug effects, Hypothalamus metabolism, Energy Metabolism drug effects, Pro-Opiomelanocortin genetics, Pro-Opiomelanocortin biosynthesis, Agouti-Related Protein genetics, Mice, Knockout, Homeostasis, GTP-Binding Protein gamma Subunits genetics, Rosiglitazone pharmacology
- Abstract
Seipin is a key regulator of lipid metabolism, the deficiency of which leads to severe lipodystrophy. Hypothalamus is the pivotal center of brain that modulates appetite and energy homeostasis, where Seipin is abundantly expressed. Whether and how Seipin deficiency leads to systemic metabolic disorders via hypothalamus-involved energy metabolism dysregulation remains to be elucidated. In the present study, we demonstrated that Seipin-deficiency induced hypothalamic inflammation, reduction of anorexigenic pro-opiomelanocortin (POMC), and elevation of orexigenic agonist-related peptide (AgRP). Importantly, administration of rosiglitazone, a thiazolidinedione antidiabetic agent, rescued POMC and AgRP expression, suppressed hypothalamic inflammation, and restored energy homeostasis in Seipin knockout mice. Our findings offer crucial insights into the mechanism of Seipin deficiency-associated energy imbalance and indicates that rosiglitazone could serve as potential intervening agent towards metabolic disorders linked to Seipin., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2024
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