Pleiotrophin Deficiency Induces Browning of Periovarian Adipose Tissue and Protects against High-Fat Diet-Induced Hepatic Steatosis

(1) Background: Pleiotrophin preserves insulin sensitivity, regulates adipose tissue lipid turnover and plasticity, energy metabolism and thermogenesis. The aim of this study was to determine the role of pleiotrophin in hepatic lipid metabolism and in the metabolic crosstalk between the liver and br...

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Main Authors: Agata Zuccaro, Begoña Zapatería, María Gracia Sánchez-Alonso, María Haro, María Limones, Gloria Terrados, Adriana Izquierdo, Patricia Corrales, Gema Medina-Gómez, Gonzalo Herradón, Julio Sevillano, María del Pilar Ramos-Álvarez
Format: Article
Language:English
Published: MDPI AG 2021-08-01
Series:International Journal of Molecular Sciences
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Online Access:https://www.mdpi.com/1422-0067/22/17/9261
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Summary:(1) Background: Pleiotrophin preserves insulin sensitivity, regulates adipose tissue lipid turnover and plasticity, energy metabolism and thermogenesis. The aim of this study was to determine the role of pleiotrophin in hepatic lipid metabolism and in the metabolic crosstalk between the liver and brown and white adipose tissue (AT) in a high-fat diet-induced (HFD) obesity mice model. (2) Methods: We analyzed circulating variables, lipid metabolism (hepatic lipid content and mRNA expression), brown AT thermogenesis (UCP-1 expression) and periovarian AT browning (brown adipocyte markers mRNA and immunodetection) in <i>Ptn</i><sup>−/−</sup> mice either fed with standard-chow diet or with HFD and in their corresponding <i>Ptn</i><sup>+/+</sup> counterparts. (3) Results: HFD-<i>Ptn<sup>−/−</sup></i> mice are protected against the development of HFD-induced insulin resistance, had lower liver lipid content and lower expression of the key enzymes involved in triacylglycerides and fatty acid synthesis in liver. HFD-<i>Ptn</i><sup>−/−</sup> mice showed higher UCP-1 expression in brown AT. Moreover, <i>Ptn</i> deletion increased the expression of specific markers of brown/beige adipocytes and was associated with the immunodetection of UCP-1 enriched multilocular adipocytes in periovarian AT. (4) Conclusions: <i>Ptn</i> deletion protects against the development of HFD-induced insulin resistance and liver steatosis, by increasing UCP-1 expression in brown AT and promoting periovarian AT browning.
ISSN:1661-6596
1422-0067