{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T10:04:34Z","timestamp":1789985074027,"version":"4.0.1"},"reference-count":30,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes for Health Research","doi-asserted-by":"publisher","award":["PJT-1665850"],"award-info":[{"award-number":["PJT-1665850"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"award":["PJT-1665850"],"award-info":[{"award-number":["PJT-1665850"]}],"id":[{"id":"https:\/\/ror.org\/01gavpb45","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Fondation de l\u2019Institut universitaire de cardiologie et de pneumologie de Qu\u00e9bec","id":[{"id":"https:\/\/ror.org\/01dq1at09","id-type":"ROR","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/01dq1at09","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biomolecules"],"abstract":"<jats:p>Background. White adipose tissue (WAT) is increasingly recognized as an endocrine organ involved in cardiovascular physiology. However, the specific contributions of distinct adipose depots to cardiac homeostasis and adaptation to pathological stress remain poorly understood. We investigated the consequences of visceral (VAT) or subcutaneous (SAT) lipectomy (Lpx) on cardiac phenotype in male and female C57BL\/6J mice and evaluated its impact on the response to a stress-inducing heart failure with preserved ejection fraction-like phenotype. Methods. VAT or SAT depot removal was performed in young adult mice. Ten weeks later, we assessed cardiac morphology, function, circulating adipokines, and left ventricular (LV) gene expression. We then exposed separate cohorts to angiotensin II infusion combined with a high-fat diet. We also conducted experiments in ovariectomized (Ovx) females to evaluate the contribution of ovarian hormones. Results. Lpx induced marked depot- and sex-specific effects on body composition, cardiac morphology, and echocardiographic parameters. Changes in LV mass, atrial size, and diastolic indices were observed despite the absence of overt pathology. These alterations were accompanied by substantial modulation of genes involved in cardiac hypertrophy, calcium handling, extracellular matrix remodelling, and energy metabolism. VAT and SAT removal also differentially affected circulating adiponectin, leptin, and MCP-1 levels. Lpx modified the cardiac hypertrophic response to cardiometabolic stress in a sex- and depot-dependent manner. Ovx altered several of these responses and was associated with evidence of increased pulmonary congestion in VAT-lipectomized females. Conclusions. These findings show that WAT contributes to maintaining cardiac homeostasis and influences adaptation to pathological stress through mechanisms highly dependent on adipose depot location, biological sex, and ovarian hormone status.<\/jats:p>","DOI":"10.3390\/biom16091364","type":"journal-article","created":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:01:38Z","timestamp":1789981298000},"page":"1364","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["White Adipose Tissue Contributes to Cardiac Homeostasis and Adaptation to Cardiometabolic Stress in a Sex- and Depot-Specific Manner"],"prefix":"10.3390","volume":"16","author":[{"given":"Sara-\u00c8ve","family":"Thibodeau","sequence":"first","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-1840-330X","authenticated-orcid":false,"given":"Nicolas","family":"Le Bos","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c9lisabeth","family":"Walsh-Wilkinson","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emylie-Ann","family":"Labb\u00e9","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audrey","family":"Morin-Grandmont","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emmy","family":"Trahan","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mathias","family":"Zakrzewski","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-8689","authenticated-orcid":false,"given":"Jacques","family":"Couet","sequence":"additional","affiliation":[{"name":"D\u00e9partement de M\u00e9decine, Facult\u00e9 de M\u00e9decine, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 0A6, Canada"},{"name":"Groupe de Recherche sur les Valvulopathies, Centre de Recherche de l\u2019Institut Universitaire de Cardiologie et de Pneumologie de Qu\u00e9bec, Universit\u00e9 Laval, Qu\u00e9bec City, QC G1V 4G5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1810","DOI":"10.1016\/j.jacc.2023.01.049","article-title":"Heart Failure with Preserved Ejection Fraction: JACC Scientific Statement","volume":"81","author":"Borlaug","year":"2023","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"200","DOI":"10.1016\/j.jacc.2016.05.019","article-title":"The HFpEF Obesity Phenotype: The Elephant in the Room","volume":"68","author":"Kitzman","year":"2016","journal-title":"J. Am. Coll. Cardiol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1648","DOI":"10.1194\/jlr.R094060","article-title":"Beyond adiponectin and leptin: Adipose tissue-derived mediators of inter-organ communication","volume":"60","author":"Funcke","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1537","DOI":"10.2337\/db06-0263","article-title":"Adipose tissue: From lipid storage compartment to endocrine organ","volume":"55","author":"Scherer","year":"2006","journal-title":"Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1038\/s41569-018-0097-6","article-title":"The role of adipose tissue in cardiovascular health and disease","volume":"16","author":"Oikonomou","year":"2019","journal-title":"Nat. Rev. Cardiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1467-789X.2009.00623.x","article-title":"Subcutaneous and visceral adipose tissue: Structural and functional differences","volume":"11","author":"Ibrahim","year":"2010","journal-title":"Obes. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1186\/s12944-018-0856-8","article-title":"Localization of fat depots and cardiovascular risk","volume":"17","author":"Gruzdeva","year":"2018","journal-title":"Lipids Health Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"758","DOI":"10.5534\/wjmh.250126","article-title":"Sex and Gender Differences in Obesity: Biological, Sociocultural, and Clinical Perspectives","volume":"43","author":"Kim","year":"2025","journal-title":"World J. Men\u2019s Health"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/j.trsl.2022.05.004","article-title":"Epididymal white adipose tissue promotes angiotensin II-induced cardiac fibrosis in an exosome-dependent manner","volume":"248","author":"Su","year":"2022","journal-title":"Transl. Res."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2951","DOI":"10.2337\/diabetes.51.10.2951","article-title":"Removal of visceral fat prevents insulin resistance and glucose intolerance of aging: An adipokine-mediated process?","volume":"51","author":"Gabriely","year":"2002","journal-title":"Diabetes"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"e00015","DOI":"10.1002\/phy2.15","article-title":"Subcutaneous adipose tissue transplantation in diet-induced obese mice attenuates metabolic dysregulation while removal exacerbates it","volume":"1","author":"Foster","year":"2013","journal-title":"Physiol. Rep."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1161\/CIRCRESAHA.121.320470","article-title":"Brown Adipocyte ADRB3 Mediates Cardioprotection via Suppressing Exosomal iNOS","volume":"131","author":"Lin","year":"2022","journal-title":"Circ. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"H1017","DOI":"10.1152\/ajpheart.00462.2023","article-title":"Cardiac reverse remodelling in a mouse model with many phenotypical features of heart failure with preserved ejection fraction: Effects of modifying lifestyle","volume":"326","author":"Aidara","year":"2024","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"e11085","DOI":"10.7717\/peerj.11085","article-title":"Segmental analysis by speckle-tracking echocardiography of the left ventricle response to isoproterenol in male and female mice","volume":"9","author":"Arsenault","year":"2021","journal-title":"PeerJ"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e17434","DOI":"10.7717\/peerj.17434","article-title":"A murine model of hypertensive heart disease in older women","volume":"12","author":"Thibodeau","year":"2024","journal-title":"PeerJ"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"H51","DOI":"10.1152\/ajpheart.00092.2025","article-title":"Relative contribution of correcting the diet and voluntary exercise to myocardial recovery in a two-hit murine model of heart failure with preserved ejection fraction","volume":"329","author":"Thibodeau","year":"2025","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1404","DOI":"10.1002\/oby.22511","article-title":"A Systematic Scoping Review of Surgically Manipulated Adipose Tissue and the Regulation of Energetics and Body Fat in Animals","volume":"27","author":"Murillo","year":"2019","journal-title":"Obes. (Silver Spring)"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2734","DOI":"10.2337\/diabetes.51.9.2734","article-title":"Androgens decrease plasma adiponectin, an insulin-sensitizing adipocyte-derived protein","volume":"51","author":"Nishizawa","year":"2002","journal-title":"Diabetes"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"136","DOI":"10.1161\/CIRCRESAHA.120.314458","article-title":"Adiponectin, Leptin and Cardiovascular Disorders","volume":"128","author":"Zhao","year":"2021","journal-title":"Circ. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1161\/CIRCULATIONAHA.118.034271","article-title":"Sex Differences in Cardiovascular Pathophysiology: Why Women Are Overrepresented in Heart Failure With Preserved Ejection Fraction","volume":"138","author":"Beale","year":"2018","journal-title":"Circulation"},{"key":"ref_21","first-page":"1","article-title":"Mechanistic Pathways of Sex Differences in Cardiovascular Disease","volume":"97","author":"Kararigas","year":"2017","journal-title":"Physiol. Rev."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6022601","DOI":"10.1155\/2022\/6022601","article-title":"Angiotensin II Promotes White Adipose Tissue Browning and Lipolysis in Mice","volume":"2022","author":"Cai","year":"2022","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Thibodeau, S.\u00c8., Labb\u00e9, E.A., Walsh-Wilkinson, \u00c9., Morin-Grandmont, A., Arsenault, M., and Couet, J. (2024). Plasma and Myocardial miRNomes Similarities and Differences during Cardiac Remodelling and Reverse Remodelling in a Murine Model of Heart Failure with Preserved Ejection Fraction. Biomolecules, 14.","DOI":"10.20944\/preprints202406.1909.v1"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"510","DOI":"10.1093\/cvr\/cvag030","article-title":"Small extracellular vesicle-mediated adipocyte-cardiomyocyte crosstalk exacerbates heart failure with preserved ejection fraction","volume":"122","author":"Pan","year":"2026","journal-title":"Cardiovasc. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e12325","DOI":"10.1111\/cpr.12325","article-title":"Inhibition of adipose tissue PPAR\u03b3 prevents increased adipocyte expansion after lipectomy and exacerbates a glucose-intolerant phenotype","volume":"50","author":"Booth","year":"2017","journal-title":"Cell Prolif."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"115732","DOI":"10.1016\/j.celrep.2025.115732","article-title":"Exploring adipose tissue-derived extracellular vesicles in inter-organ crosstalk: Implications for metabolic regulation and adipose tissue function","volume":"44","author":"Scherer","year":"2025","journal-title":"Cell Rep."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"D\u2019Oria, R., Genchi, V.A., Caccioppoli, C., Calderoni, I., Marrano, N., Biondi, G., Borrelli, A., Di Gioia, L., Giorgino, F., and Laviola, L. (2022). Impact of Dysfunctional Adipose Tissue Depots on the Cardiovascular System. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms232214296"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1002\/oby.23601","article-title":"Metabolic effects of lipectomy and of adipose tissue transplantation","volume":"31","author":"Davis","year":"2023","journal-title":"Obesity (Silver Spring)"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"McFadden, S.A., Fang, Y., Quinn, K., Peck, M.R., Chapman, J.E., Hill, T., Bartke, A., Hascup, E.R., and Hascup, K.N. (2026). Surgical removal of visceral adipose tissue has therapeutic benefit in male APPNL-F mice. Front. Endocrinol., 17.","DOI":"10.3389\/fendo.2026.1681801"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2854","DOI":"10.1007\/s11695-025-08000-6","article-title":"Reductions in Epicardial Adipose Tissue and Mediastinal Fat Are Associated with Improved Cardiac Function","volume":"35","author":"Tanahashi","year":"2025","journal-title":"Obes. Surg."}],"container-title":["Biomolecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1364\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T09:58:01Z","timestamp":1789984681000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2218-273X\/16\/9\/1364"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":30,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["biom16091364"],"URL":"https:\/\/doi.org\/10.3390\/biom16091364","relation":{},"ISSN":["2218-273X"],"issn-type":[{"value":"2218-273X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]}}}