{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T05:24:27Z","timestamp":1782451467963,"version":"3.54.5"},"reference-count":56,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T00:00:00Z","timestamp":1735603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Japanese Ministry of Health, Labour, and Welfare","award":["22K08661"],"award-info":[{"award-number":["22K08661"]}]},{"name":"Daiwa Securities Health Foundation","award":["22K08661"],"award-info":[{"award-number":["22K08661"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background\/Objectives: Endothelial peroxisome proliferator-activated receptor gamma (PPAR\u03b3) 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 PPAR\u03b3 revealed that ghrelin\/GHSR signaling in endothelial cells promoted lipid uptake via endothelial PPAR\u03b3. Conclusions: Endothelial GHSR is key for regulating lipid metabolism via PPAR\u03b3 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.<\/jats:p>","DOI":"10.3390\/nu17010146","type":"journal-article","created":{"date-parts":[[2024,12,31]],"date-time":"2024-12-31T07:00:37Z","timestamp":1735628437000},"page":"146","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Ghrelin Promotes Lipid Uptake into White Adipose Tissue via Endothelial Growth Hormone Secretagogue-Receptor in Mice"],"prefix":"10.3390","volume":"17","author":[{"given":"Hidenori","family":"Urai","sequence":"first","affiliation":[{"name":"Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiko","family":"Azegami","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Motoaki","family":"Komatsu","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rina","family":"Takahashi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshiaki","family":"Kubota","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Hasegawa","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Tokushima University School of Medicine, Tokushima-shi 770-8503, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hirofumi","family":"Tokuyama","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Tokyo Dental University Ichikawa General Hospital, Ichikawa-shi 272-8513, Chiba, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu","family":"Wakino","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Department of Internal Medicine, Tokushima University School of Medicine, Tokushima-shi 770-8503, Tokushima, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaori","family":"Hayashi","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kanda","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"},{"name":"Division of Nephrology, Department of Internal Medicine, Faculty of Medicine, Shimane University, Matsue 693-8501, Shimane, Japan"},{"name":"The Center for Integrated Kidney Research and Advance (IKRA), Faculty of Medicine, Shimane University, Matsue 693-8501, Shimane, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2514-4919","authenticated-orcid":false,"given":"Hiroshi","family":"Itoh","sequence":"additional","affiliation":[{"name":"Division of Nephrology, Endocrinology and Metabolism, Department of Internal Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo 160-8582, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Emerging Risk Factors Collaboration (2022). 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