{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:21:46Z","timestamp":1770394906929,"version":"3.49.0"},"reference-count":55,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T00:00:00Z","timestamp":1770163200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Cancer is a multifactorial disease influenced not only by genetic and epigenetic alterations but also by interactions with the surrounding microenvironment. Among the hallmarks of cancer, metabolic reprogramming enables tumor cells to adapt and survive under adverse conditions. These metabolic alterations also induce changes in stromal cells. In clear cell renal cell carcinoma (ccRCC), adipocytes are among the most abundant stromal components. We have previously shown that ccRCC progression depends on the bidirectional crosstalk between tumor epithelial cells and neighboring adipocytes. Here, we investigated the effects of ccRCC on na\u00efve human adipose tissue (hRAN). Human retroperitoneal adipose tissue fragments from two distinct donors (n = 2) were incubated with conditioned media (CMs) derived from ccRCC tumors (T-CM) or renal epithelial cells (Tc-CM). We analyzed the expression of adipocytokines, differentiation and browning markers, metabolic parameters, and steroid hormone receptor profiles. The exposure of hRAN to T-CM or Tc-CM led to significant alterations in the expression of adiponectin and leptin, as well as markers associated with differentiation and browning, including PLIN1, HSL, PGC1\u03b1, PPAR\u03b3, and UCP1. Adipocytes from treated hRAN were smaller than those from controls, suggesting dedifferentiation. Moreover, expression of FABP4 and MCT1 was significantly increased in explants treated with T-CM compared to control media. Conditioned media from these treated hRAN samples showed elevated lactate secretion, indicating enhanced lactatogenesis. Given the role of sex hormones in metabolic regulation, we examined the expression of estrogen (ER), androgen (AR), and progesterone (PR) receptors. While AR and PR levels remained unchanged, both ER\u03b1 and ER\u03b2 were significantly upregulated after T-CM treatment. Metabolic reprogramming in renal tumors induces profound adaptive changes in adjacent adipose tissue. The dedifferentiation and browning of adipocytes, altered adipocytokine expression, and increased lactate production observed in hRAN reflect the metabolic stress imposed by the tumor environment. Here, we provide evidence, using an ex vivo model, of a dynamic partnership between human adipose tissue and ccRCC tumors.<\/jats:p>","DOI":"10.3390\/ijms27031528","type":"journal-article","created":{"date-parts":[[2026,2,4]],"date-time":"2026-02-04T12:51:56Z","timestamp":1770209516000},"page":"1528","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adipose Tissue and Renal Carcinoma: A Protumor Metabolic and Endocrine Alliance"],"prefix":"10.3390","volume":"27","author":[{"given":"Mat\u00edas","family":"Ferrando","sequence":"first","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daiana Lorena Moya","family":"Moya Morales","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1312-9498","authenticated-orcid":false,"given":"Leonardo Rafael","family":"Romeo","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"},{"name":"Urocuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mauro Agust\u00edn","family":"Carrillo","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Roc\u00edo Yasmin","family":"Cano","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvina Esther","family":"G\u00f3mez","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0772-0153","authenticated-orcid":false,"given":"Constanza Matilde","family":"L\u00f3pez-Fontana","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rub\u00e9n Walter","family":"Car\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2309-0398","authenticated-orcid":false,"given":"Flavia Alejandra","family":"Bruna","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"},{"name":"Centro de Investigaciones Odontol\u00f3gicas, Facultad de Odontolog\u00eda, Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Virginia","family":"Pistone-Creydt","sequence":"additional","affiliation":[{"name":"Instituto de Medicina y Biolog\u00eda Experimental de Cuyo (IMBECU), Centro Cient\u00edfico y Tecnol\u00f3gico Mendoza, Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Cuyo, Mendoza M5500, Argentina"},{"name":"Instituto de Fisiolog\u00eda, Facultad de Ciencias M\u00e9dicas, Universidad Nacional de Cuyo, Mendoza M5500, Argentina"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/j.cell.2011.02.013","article-title":"Hallmarks of cancer: The next generation","volume":"144","author":"Hanahan","year":"2011","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1016\/j.canlet.2018.08.006","article-title":"Fatty acid oxidation: An emerging facet of metabolic transformation in cancer","volume":"435","author":"Ma","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1126\/science.123.3191.309","article-title":"On the origin of cancer 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