Glial Fatty Acid-Binding Protein 7 (FABP7) Regulates Neuronal Leptin Sensitivity in the Hypothalamic Arcuate Nucleus
The hypothalamus is involved in the regulation of food intake and energy homeostasis. The arcuate nucleus (ARC) and median eminence (ME) are the primary hypothalamic sites that sense leptin and nutrients in the blood, thereby mediating food intake. Recently, studies demonstrating a role for non-neuronal cell types, including astrocytes and tanycytes, in these regulatory processes have begun to emerge. However, the molecular mechanisms involved in these activities remain largely unknown. In this study, we examined in detail the localization of fatty acid-binding protein 7 (FABP7) in the hypothalamic ARC and sought to determine its role in the hypothalamus. We performed a phenotypic analysis of diet-induced FABP7 knockout (KO) obese mice and of FABP7 KO mice treated with a single leptin injection. Immunohistochemistry revealed that FABP7+ cells are NG2+ or GFAP+ in the ARC and ME. In mice fed a high-fat diet, weight gain and food intake were lower in FABP7 KO mice than in wild-type (WT) mice. FABP7 KO mice also had lower food intake and weight gain after a single injection of leptin, and we consistently confirmed that the number of pSTAT3+ cells in the ARC indicated that the leptin-induced activation of neurons was significantly more frequent in FABP7 KO mice than in WT mice. In FABP7 KO mice-derived primary astrocyte cultures, the level of ERK phosphorylation was lower after leptin treatment. Collectively, these results indicate that in hypothalamic astrocytes, FABP7 might be involved in sensing neuronal leptin via glia-mediated mechanisms and plays a pivotal role in controlling systemic energy homeostasis.
KeywordsGlia Hypothalamus Arcuate nucleus Leptin Obesity Fatty acid-binding protein
We thank Professor W. Stallcup for gifting the anti-NG2 and anti-PDGFRα antibodies. This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 16K12735, 16H06616 and Tohoku University Center for the Gender Equality Promotion Start-up Grant.
Compliance with Ethical Standards
All experimental procedures involving mice were approved by the Institute of Laboratory Animals of Tohoku University Graduate School of Medicine and carried out according to the Guidelines for Animal Experimentation of the Tohoku University Graduate School of Medicine and according to the laws and notification requirements of the Japanese government.
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