Next Article in Journal
DAG-MAG-ΒHB: A Novel Ketone Diester Modulates NLRP3 Inflammasome Activation in Microglial Cells in Response to Beta-Amyloid and Low Glucose AD-like Conditions
Previous Article in Journal
Diet and Lifestyle Factors and Incident Acute Mesenteric Ischemia—A Prospective Cohort Study
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Nutrients
Volume 17
Issue 1
10.3390/nu17010146
nutrients-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Article

Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice

by
Hidenori Urai
1,
Tatsuhiko Azegami
1,*,
Motoaki Komatsu
1,
Rina Takahashi
1,
Yoshiaki Kubota
2,
Kazuhiro Hasegawa
3,
Hirofumi Tokuyama
4,
Shu Wakino
3,
Kaori Hayashi
1,
Takeshi Kanda
1,5,6,* and
Hiroshi Itoh
1
1
Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
2
Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan
3
Division of Nephrology, Department of Internal Medicine, Tokushima University School of Medicine, Tokushima-shi 770-8503, Tokushima, Japan
4
Department of Internal Medicine, Tokyo Dental University Ichikawa General Hospital, Ichikawa-shi 272-8513, Chiba, Japan
5
Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Shimane University, Matsue 693-8501, Shimane, Japan
6
The Center for Integrated Kidney Research and Advance (IKRA), Faculty of Medicine, Shimane University, Matsue 693-8501, Shimane, Japan
*
Authors to whom correspondence should be addressed.
Nutrients 2025, 17(1), 146; https://doi.org/10.3390/nu17010146
Submission received: 14 December 2024 / Revised: 28 December 2024 / Accepted: 30 December 2024 / Published: 31 December 2024
(This article belongs to the Section Lipids)
Browse Figures
Versions Notes

Abstract

Background/Objectives: Endothelial peroxisome proliferator-activated receptor gamma (PPARγ) regulates adipose tissue by facilitating lipid uptake into white adipocytes, but the role of endothelial lipid transport in systemic energy balance remains unclear. Ghrelin conveys nutritional information through the central nervous system and increases adiposity, while deficiency in its receptor, growth hormone secretagogue-receptor (GHSR), suppresses adiposity on a high-fat diet. This study aims to examine the effect of ghrelin/GHSR signaling in the endothelium on lipid metabolism. Methods: We compared the effects of ghrelin on adiposity and lipid uptake into adipocytes in wild-type and GHSR-null mice. Transgenic mice expressing GHSR selectively in endothelial cells were also generated and compared with global GHSR-null and wild-type mice. The impact of ghrelin on lipid uptake-related genes was assessed in cultured endothelial cells. Results: Ghrelin increased adiposity and triglyceride clearance in wild-type but not in GHSR-null mice. GHSR-null mice showed higher serum triglyceride after olive oil gavage and lower white adipose tissue (WAT) weight on a high-fat diet, suggesting impaired lipid uptake. Restoring GHSR expression in endothelial cells increased lipoprotein lipase activity, lipid uptake into WAT, and WAT weight. Ghrelin enhanced free fatty acid uptake and the expression of lipid uptake genes in cultured endothelial cells, whereas these effects were absent in GHSR-null mice-derived endothelial cells. Knockdown of PPARγ revealed that ghrelin/GHSR signaling in endothelial cells promoted lipid uptake via endothelial PPARγ. Conclusions: Endothelial GHSR is key for regulating lipid metabolism via PPARγ in response to ghrelin and for the role of endothelium in regulating white adipocyte metabolism. Targeting endothelial ghrelin signaling may be a promising therapeutic approach for managing excessive adiposity and associated metabolic disorders.
Keywords: endothelial cells; ghrelin; growth hormone secretagogue-receptor; obesity; triglyceride endothelial cells; ghrelin; growth hormone secretagogue-receptor; obesity; triglyceride
Graphical Abstract

Share and Cite

MDPI and ACS Style

Urai, H.; Azegami, T.; Komatsu, M.; Takahashi, R.; Kubota, Y.; Hasegawa, K.; Tokuyama, H.; Wakino, S.; Hayashi, K.; Kanda, T.; et al. Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice. Nutrients 2025, 17, 146. https://doi.org/10.3390/nu17010146

AMA Style

Urai H, Azegami T, Komatsu M, Takahashi R, Kubota Y, Hasegawa K, Tokuyama H, Wakino S, Hayashi K, Kanda T, et al. Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice. Nutrients. 2025; 17(1):146. https://doi.org/10.3390/nu17010146

Chicago/Turabian Style

Urai, Hidenori, Tatsuhiko Azegami, Motoaki Komatsu, Rina Takahashi, Yoshiaki Kubota, Kazuhiro Hasegawa, Hirofumi Tokuyama, Shu Wakino, Kaori Hayashi, Takeshi Kanda, and et al. 2025. "Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice" Nutrients 17, no. 1: 146. https://doi.org/10.3390/nu17010146

APA Style

Urai, H., Azegami, T., Komatsu, M., Takahashi, R., Kubota, Y., Hasegawa, K., Tokuyama, H., Wakino, S., Hayashi, K., Kanda, T., & Itoh, H. (2025). Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice. Nutrients, 17(1), 146. https://doi.org/10.3390/nu17010146

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop