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Hence, defects in PPAR\u03b3 have been associated to the development of metabolic disorders. Sex hormone-binding globulin (SHBG) is a glycoprotein primarily produced in the liver that regulates the bioavailability of sex hormones. Alike PPAR\u03b3, low SHBG levels have been correlated with insulin resistance and associated endocrine abnormalities. Therefore, this study aimed to verify whether SHBG may restore depleted PPAR\u03b3 functions and thus serve as a new candidate for the management of metabolic conditions. A model of equine adipose-derived stromal cells (EqASCs) has been used, in which a PPAR\u03b3 silencing and SHBG treatment have been achieved to determine the changes in cell viability, premature senescence, oxidative stress, and mitochondrial functions. Obtained data demonstrated that loss in PPAR\u03b3 triggers cell apoptosis which is not reversed by SHBG application. Moreover, PPAR\u03b3 knockdown cells exhibited premature senescence, which has been substantially alleviated by SHBG concomitantly to increased BAX\/BCL2 ratio, suggesting a possible effect on senescence-induced apoptosis resistance. Interestingly, PPAR\u03b3 silencing induced a significant alteration in mitochondrial membrane potential as well as the expression of dynamics and metabolism-related markers. SHBG treatment enabled to ameliorate the transmembrane potential, to normalize the expression levels of key dynamics and metabolism mediators, and to restore the protein levels of PINK, which is critically involved in mitochondria recycling machinery. Presented data suggest that SHBG may provide new mechanistic insights into the regulation of PPAR\u03b3 functions, and thus offers a preliminary picture on a possible SHBG-PPAR\u03b3 metabolic crosstalk.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>\n                           <jats:bold>Key messages<\/jats:bold>\n                        <\/jats:title>\n                <jats:p><jats:list list-type=\"bullet\">\n                  <jats:list-item>\n                    <jats:p>PPAR\u03b3 is a transcription factor that tightly regulates cell metabolism.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>Low SHBG levels correlate with insulin resistance and associated endocrine abnormalities.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>PPAR\u03b3 silencing reduces cell viability, triggers premature senescence and profound mitochondrial failure in equine ASCs.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>SHBG protein reverses senescent phenotype and apoptosis resistance of PPAR\u03b3- ASCs.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>SHBG improves mitochondrial dynamics and metabolism following PPAR\u03b3 knockdown.<\/jats:p>\n                  <\/jats:list-item>\n                  <jats:list-item>\n                    <jats:p>SHBG might serve as a PPAR\u03b3 potential mimicking agent for the modulation of ASCs metabolic processes. <\/jats:p>\n                  <\/jats:list-item>\n                <\/jats:list><\/jats:p>\n              <\/jats:sec>","DOI":"10.1007\/s00109-024-02459-z","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T12:02:09Z","timestamp":1718366529000},"page":"1015-1036","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Sex hormone binding globulin (SHBG) modulates mitochondrial dynamics in PPAR\u03b3-depleted equine adipose derived stromal cells"],"prefix":"10.1007","volume":"102","author":[{"given":"Krzysztof","family":"Marycz","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benita","family":"Wiatrak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer M.","family":"Irwin-Houston","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Klaudia","family":"Marcinkowska","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Malwina","family":"Mularczyk","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9914-2903","authenticated-orcid":false,"given":"Lynda","family":"Bourebaba","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"2459_CR1","doi-asserted-by":"publisher","first-page":"423","DOI":"10.1089\/met.2015.0095","volume":"13","author":"P Manna","year":"2015","unstructured":"Manna P, Jain SK (2015) Obesity, oxidative stress, adipose tissue dysfunction, and the associated health risks: causes and therapeutic strategies. 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