{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T09:04:47Z","timestamp":1784192687841,"version":"3.55.0"},"reference-count":71,"publisher":"The Endocrine Society","issue":"8","license":[{"start":{"date-parts":[[2026,7,3]],"date-time":"2026-07-03T00:00:00Z","timestamp":1783036800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01DK142092"],"award-info":[{"award-number":["R01DK142092"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P30DK127984"],"award-info":[{"award-number":["P30DK127984"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The transcriptional landscape of the gastric mucosa in response to opposing nutritional states remains poorly defined. Here, we profiled gastric mucosal gene expression changes induced by diet-induced obesity (DIO) and calorie restriction (CR) in mice and investigated the physiological role of Decidual Protein Induced by Progesterone 1 (Depp1) using newly generated Depp1-knockout (KO) mice. RNA sequencing revealed that DIO elicits a predominantly proinflammatory transcriptional program in the gastric mucosa, whereas CR upregulates genes involved in peptide transport and extracellular matrix organization while downregulating immunity-related pathways. Among CR-induced genes, Depp1 exhibited the strongest positive correlation with expression of gene encoding the gastric hormone ghrelin. qRT-PCR confirmed enrichment of Depp1 in gastric ghrelin cells and demonstrated CR-induced upregulation of Depp1 in additional tissues, including liver, kidney, and pancreas; notably, hepatic induction by CR was absent in ghrelin-KO mice. Despite this association, Depp1-KO mice displayed normal metabolic responses to CR, including preserved glucose homeostasis. In contrast, following 16 weeks of ad libitum high-fat diet feeding, male Depp1-KO mice exhibited greater weight gain, hyperphagia, increased fat and lean mass, and impaired glucose tolerance compared with wild-type littermates. These phenotypes were accompanied by selective hepatic gene expression changes affecting Pgc1a, Pck1, and Igf1. Collectively, these findings identify Depp1 as a CR-induced, ghrelin-associated gene that influences hepatic transcriptional responses yet is dispensable for short-term adaptation to CR, while also implicating Depp1 as a protective factor against metabolic dysfunction during DIO through mechanisms that remain to be defined.<\/jats:p>","DOI":"10.1210\/endocr\/bqag075","type":"journal-article","created":{"date-parts":[[2026,7,2]],"date-time":"2026-07-02T11:37:58Z","timestamp":1782992278000},"source":"Crossref","is-referenced-by-count":0,"title":["Loss of the calorie restriction response protein DEPP1 worsens diet-induced obesity"],"prefix":"10.1210","volume":"167","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-8094","authenticated-orcid":false,"given":"Sepideh","family":"Sheybani-Deloui","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Center for Hypothalamic Research, University of Texas Southwestern Medical Center , Dallas, TX 75390-9030 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