{"id":107432,"date":"2024-03-25T20:37:08","date_gmt":"2024-03-26T00:37:08","guid":{"rendered":"https:\/\/med.virginia.edu\/cell-biology\/?p=107432"},"modified":"2026-07-09T12:55:34","modified_gmt":"2026-07-09T16:55:34","slug":"obesogenic-diet-disrupts-tissue-specific-mitochondrial-gene-signatures-in-the-artery-and-capillary-endothelium","status":"publish","type":"post","link":"https:\/\/med.virginia.edu\/cell-biology\/2024\/03\/25\/obesogenic-diet-disrupts-tissue-specific-mitochondrial-gene-signatures-in-the-artery-and-capillary-endothelium\/","title":{"rendered":"Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium"},"content":{"rendered":"<p><strong>UVA Author:<\/strong> Nicholas Chavkin<br \/>\n<strong>Citation:<\/strong> Dunaway LS, Luse MA, Nyshadham S, Bulut G, Alencar GF, Chavkin NW, Cortese-Krott M, Hirschi KK, Isakson BE. Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium. Physiol Genomics. 2024 Feb 1;56(2):113-127. doi: 10.1152\/physiolgenomics.00109.2023. Epub 2023 Nov 20. PMID: 37982169.<\/p>\n<p><strong>DOI:<\/strong> <a>https:\/\/journals.physiology.org\/doi\/full\/10.1152\/physiolgenomics.00109.2023<\/a><br \/>\n<strong>Pub-Med Number<\/strong>: 37982169<\/p>\n<hr \/>\n<p>Endothelial cells (ECs) adapt to the unique needs of their resident tissue and metabolic perturbations, such as obesity. We sought to understand how obesity affects EC metabolic phenotypes, specifically mitochondrial gene expression. We investigated the mesenteric and adipose endothelium because these vascular beds have distinct roles in lipid homeostasis. Initially, we performed bulk RNA sequencing on ECs from mouse adipose and mesenteric vasculatures after a normal chow (NC) diet or high-fat diet (HFD) and found higher mitochondrial gene expression in adipose ECs compared with mesenteric ECs in both NC and HFD mice. Next, we performed single-cell RNA sequencing and categorized ECs as arterial, capillary, venous, or lymphatic. We found mitochondrial genes to be enriched in adipose compared with mesentery under NC conditions in artery and capillary ECs. After HFD, these genes were decreased in adipose ECs, becoming like mesenteric ECs. Transcription factor analysis revealed that peroxisome proliferator-activated receptor-\u03b3 (PPAR-\u03b3) had high specificity in NC adipose artery and capillary ECs. These findings were recapitulated in single-nuclei RNA-sequencing data from human visceral adipose. The sum of these findings suggests that mesenteric and adipose arterial ECs metabolize lipids differently, and the transcriptional phenotype of the vascular beds converges in obesity due to downregulation of PPAR-\u03b3 in adipose artery and capillary ECs.NEW &amp; NOTEWORTHY Using bulk and single-cell RNA sequencing on endothelial cells from adipose and mesentery, we found that an obesogenic diet induces a reduction in adipose endothelial oxidative phosphorylation gene expression, resulting in a phenotypic convergence of mesenteric and adipose endothelial cells. Furthermore, we found evidence that PPAR-\u03b3 drives this phenotypic shift. Mining of human data sets segregated based on body mass index supported these findings. These data point to novel mechanisms by which obesity induces endothelial dysfunction.<\/p>\n","protected":false},"excerpt":{"rendered":"<p>UVA Author: Nicholas Chavkin Citation: Dunaway LS, Luse MA, Nyshadham S, Bulut G, Alencar GF, Chavkin NW, Cortese-Krott M, Hirschi KK, Isakson BE. Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium. Physiol Genomics. 2024 Feb 1;56(2):113-127. doi: 10.1152\/physiolgenomics.00109.2023. Epub 2023 Nov 20. PMID: 37982169. DOI: https:\/\/journals.physiology.org\/doi\/full\/10.1152\/physiolgenomics.00109.2023 Pub-Med Number: 37982169 Endothelial [&hellip;]<\/p>\n","protected":false},"author":1740,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":"","_members_access_role":[],"_members_access_error":"","_links_to":"","_links_to_target":""},"categories":[13],"tags":[23],"class_list":["post-107432","post","type-post","status-publish","format-standard","hentry","category-featured-publications","tag-department-news"],"acf":false,"yoast_head":"<!-- This site is optimized with the Yoast SEO plugin v28.1 - https:\/\/yoast.com\/product\/yoast-seo-wordpress\/ -->\n<title>Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium - Department of Cell Biology<\/title>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/med.virginia.edu\/cell-biology\/2024\/03\/25\/obesogenic-diet-disrupts-tissue-specific-mitochondrial-gene-signatures-in-the-artery-and-capillary-endothelium\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium - Department of Cell Biology\" \/>\n<meta property=\"og:description\" content=\"UVA Author: Nicholas Chavkin Citation: Dunaway LS, Luse MA, Nyshadham S, Bulut G, Alencar GF, Chavkin NW, Cortese-Krott M, Hirschi KK, Isakson BE. Obesogenic diet disrupts tissue-specific mitochondrial gene signatures in the artery and capillary endothelium. Physiol Genomics. 2024 Feb 1;56(2):113-127. doi: 10.1152\/physiolgenomics.00109.2023. Epub 2023 Nov 20. PMID: 37982169. 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