Pleiotrophin deletion alters glucose homeostasis, energy metabolism and brown fat thermogenic function in mice

dc.contributor.authorSevillano, julio
dc.contributor.authorSánchez-Alonso, Maria Gracia
dc.contributor.authorZapateria, begoña
dc.contributor.authorcalderon, maria
dc.contributor.authoralcala, maria
dc.contributor.authorlimones, maria
dc.contributor.authorpita, jimena
dc.contributor.authorgramage, esther
dc.contributor.authorvivente-rodriguez, marta
dc.contributor.authorHorrillo, Daniel
dc.contributor.authorMedina-gomez, Gema
dc.contributor.authorObregon, maria jesus
dc.contributor.authorviana, marta
dc.contributor.authorvalladoliz-acebes, Ismael
dc.contributor.authorherradon, gonzalo
dc.contributor.authorRamos-alvarez, pilar
dc.date.accessioned2024-01-25T05:41:30Z
dc.date.available2024-01-25T05:41:30Z
dc.date.issued2019-08-22
dc.description.abstractAbstract Aims/hypothesis Pleiotrophin, a developmentally regulated and highly conserved cytokine, exerts different functions including regulation of cell growth and survival. Here, we hypothesise that this cytokine can play a regulatory role in glucose and lipid homeostasis. Methods To test this hypothesis, we performed a longitudinal study characterising the metabolic profile (circulating variables and tissue mRNA expression) of gene-targeted Ptn-deficient female mice and their corresponding wild-type counterparts at different ages from young adulthood (3 months) to older age (15 months). Metabolic cages were used to investigate the respiratory exchange ratio and energy expenditure, at both 24ºC and 30ºC. Undifferentiated immortalised mouse brown adipocytes (mBAs) were treated with 0.1 µg/ml pleiotrophin until day 6 of differentiation, and markers of mBA differentiation were analysed by quantitative real-time PCR (qPCR). Results Ptn deletion was associated with a reduction in total body fat (20.2% in Ptn +t+ vs 13.9% in Ptn -I- mice) and an enhanced lipolytic response to isoprenaline in isolated adipocytes from 15-month-old mice (189% in Ptn+t+ vs 273% in Ptn _1_ mice). We found that Ptn -t- mice exhibited a significantly lower QUICK.l value and an altered lipid profile; plasma triacylglycerols and NEFA did not increase with age, as happens in Ptn+t+ mice. Furthermore, the contribution of cold-induced thermogenesis to energy expenditure was greater in Ptn -I- than Ptn +!+ mice ( 42.6% and 33.6%, respectively). Body temperature and the activity and expression of deiodinase, T 3 and mitochondrial uncoupling protein-1 in the brown adipose tissue of Ptn _,_ mice were higher than in wild-type controls. Finally, supplementing brown pre-adipocytes with pleiotrophin decreased the expression ofthe brown adipocyte markers Cidea (20% reduction), Prdml 6 (21 % reduction), and Pgcl-a (also known as Ppargcl a, 11 % reduction). Conclusions/interpretation Our results revea] for the first time that pleiotrophin is a key player in preserving insulin sensitivity, driving the dynarnics of adipose tissue lipid turnover and plasticity, and regulating energy metabolism and thermogenesis. These findings open therapeutic avenues for the treatrnent of metabolic disorders by targeting pleiotrophin in the crosstalk between white and brown adipose tissue.es
dc.identifier.citationSevillano, J., Sánchez-Alonso, M.G., Zapatería, B. et al. Pleiotrophin deletion alters glucose homeostasis, energy metabolism and brown fat thermogenic function in mice. Diabetologia 62, 123–135 (2019). https://doi.org/10.1007/s00125-018-4746-4es
dc.identifier.doi10.1007/s00125-018-4746-4es
dc.identifier.issn0012-186X
dc.identifier.urihttps://hdl.handle.net/10115/28868
dc.language.isoenges
dc.publisherSpringer-Verlages
dc.rights.accessRightsinfo:eu-repo/semantics/restrictedAccesses
dc.subjectAdipose tissuees
dc.subjectGlucose homeostasises
dc.subjectnsulin resistance • Metabolismes
dc.titlePleiotrophin deletion alters glucose homeostasis, energy metabolism and brown fat thermogenic function in micees
dc.typeinfo:eu-repo/semantics/articlees

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