Glial Fatty Acid-Binding Protein 7 (FABP7) Regulates Neuronal Leptin Sensitivity in the Hypothalamic Arcuate Nucleus

  • Yuki Yasumoto
  • Hirofumi Miyazaki
  • Masaki Ogata
  • Yoshiteru Kagawa
  • Yui Yamamoto
  • Ariful Islam
  • Tetsuya Yamada
  • Hideki Katagiri
  • Yuji Owada
Article
  • 104 Downloads

Abstract

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.

Keywords

Glia Hypothalamus Arcuate nucleus Leptin Obesity Fatty acid-binding protein 

Notes

Acknowledgments

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.

Supplementary material

12035_2018_1033_Fig7_ESM.gif (54 kb)
Supplemental Fig. 1

WAT and T-CHO were significantly lower in FABP7 KO mice than in WT mice fed a HFD for 12 weeks. (a) Weight of EWAT (g), (b-f) Serum blood glucose (mg/dL), TG (mg/dL), FFA (mg/dL), T-CHO (mg/dL), and ALT (mg/dL) levels in WT and FABP7 KO mice fed a control diet or HFD. The data are presented as the mean ± SEM (n = 5) and are representative of three independent experiments. *p < 0.05, analyzed using Student’s t tests. (GIF 54 kb)

12035_2018_1033_MOESM1_ESM.tif (920 kb)
High resolution image (TIFF 919 kb)
12035_2018_1033_Fig8_ESM.gif (89 kb)
Supplemental Fig. 2

HFD did not alter FABP7 levels in the ARC and ME. (a) qPCR results showing the expression of FABP7 in the ARC and ME. The data are presented as the mean ± SEM (n = 4) and were analyzed using Student’s t tests. STD: standard diet, HFD: high fat diet (b) The total number of FABP7+ cells in the ARC. The data are presented as the mean ± SEM in 4 sections (n = 4) and were analyzed using Student’s t tests. (c) Representative images of FABP7 labeling in the ARC and ME. Scale bars = 50 μm. (GIF 89 kb)

12035_2018_1033_MOESM2_ESM.tif (1.1 mb)
High resolution image (TIFF 1173 kb)

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Authors and Affiliations

  1. 1.Department of Organ AnatomyTohoku University Graduate School of MedicineSendaiJapan
  2. 2.Department of Metabolism and DiabetesTohoku University Graduate School of MedicineSendaiJapan

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