{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:31:18Z","timestamp":1789605078540,"version":"build-2803163510"},"reference-count":46,"publisher":"American Diabetes Association","issue":"11","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100019210","name":"UHN Foundation","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100019210","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2025,11,1]]},"abstract":"<jats:sec>\n                    <jats:title\/>\n                    <jats:p>Growth differentiation factor 15 (GDF15) is an anorectic and weight loss\u2013inducing hormone that responds to stimuli such as endoplasmic reticulum stress, exercise, metformin, and, more recently, dietary lipids. Given its potential as an antiobesogenic agent, we examined how endogenous GDF15 responds to an Intralipid infusion in different organs to regulate food intake in\u00a0vivo. We found that an acute Intralipid infusion into the upper small intestine (USI) inhibited food intake and increased plasma GDF15, as well as kidney and hepatic Gdf15 expression in chow-fed but not high-fat (HF)\u2013induced hyperphagic male rats. Kidney Gdf15 knockdown blunted Intralipid-induced increases in kidney and plasma GDF15 levels as well as its feeding-lowering effects, while hepatic Gdf15 expression remained unaffected. Lastly, we knocked down GDNF family receptor \u03b1-like (Gfral) in the area postrema, which negated the feeding-lowering effect of Intralipid despite a rise in plasma GDF15 levels in chow rats. In summary, we report that kidney GDF15 is necessary for USI intralipid sensing to trigger an area postrema axis to inhibit food intake. We propose that HF feeding impairs acute lipid sensing to lower feeding by negating the lipid-regulatory effect on kidney GDF15.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Article Highlights<\/jats:title>\n                    <jats:p>Upper small intestine lipid infusion increases kidney, hepatic, and plasma growth differentiation factor 15 (GDF15) levels in chow but not high-fat rats. Upper small intestine lipid infusion lowers food intake in chow but not high-fat rats. Knockdown of kidney Gdf15 negates lipids to increase plasma GDF15 and lower feeding. Knockdown of GDNF family receptor \u03b1-like (Gfral) in the area postrema negates lipid anorectic effect.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.2337\/db25-0174","type":"journal-article","created":{"date-parts":[[2025,8,29]],"date-time":"2025-08-29T02:42:01Z","timestamp":1756435321000},"page":"1918-1928","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":5,"title":["Lipids Engage a Kidney-Brain GDF15 Axis to Suppress Food Intake"],"prefix":"10.2337","volume":"74","author":[{"given":"Ameth N.","family":"Garrido","sequence":"first","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network 1 , Toronto, Ontario, Canada"},{"name":"Department of Physiology, University of Toronto 2 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Song-Yang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network 1 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyla","family":"Bruce","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network 1 , Toronto, Ontario, Canada"},{"name":"Institute of Medical Science, University of Toronto 3 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charmaine S.H.","family":"Lai","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network 1 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeyu","family":"Yang","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network 1 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa T.","family":"Wang","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network 1 , Toronto, Ontario, Canada"},{"name":"Department of Physiology, University of Toronto 2 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2908-3324","authenticated-orcid":false,"given":"Tony K.T.","family":"Lam","sequence":"additional","affiliation":[{"name":"Toronto General Hospital Research Institute, University Health Network 1 , Toronto, Ontario, Canada"},{"name":"Department of Physiology, University of Toronto 2 , Toronto, Ontario, Canada"},{"name":"Institute of Medical Science, University of Toronto 3 , Toronto, Ontario, Canada"},{"name":"Department of Medicine, University of Toronto, Toronto 4 , Ontario, Canada"},{"name":"Banting and Best Diabetes Centre, University of Toronto 5 , Toronto, Ontario, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1167","published-online":{"date-parts":[[2025,8,28]]},"reference":[{"key":"2026061115073827900_B1","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.tem.2024.09.002","article-title":"GDF15 is still a mystery hormone","volume":"36","author":"Sigvardsen","year":"2025","journal-title":"Trends Endocrinol Metab"},{"key":"2026061115073827900_B2","doi-asserted-by":"crossref","first-page":"13760","DOI":"10.1074\/jbc.273.22.13760","article-title":"Cloning and characterization of a novel member of the transforming growth factor-beta\/bone morphogenetic protein family","volume":"273","author":"Paralkar","year":"1998","journal-title":"J Biol Chem"},{"key":"2026061115073827900_B3","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1016\/j.cmet.2018.12.016","article-title":"GDF15 provides an endocrine signal of nutritional stress in mice and 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