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

Agata Zuccaro,Begoña Zapatería,María Gracia Sánchez-Alonso,María Limones,Adriana Izquierdo,Julio Sevillano,Gonzalo Herradón,María Haro,Gloria Terrados,María Del Pilar Ramos-Álvarez,Gema Medina-Gómez,Patricia Corrales

doi:10.3390/ijms22179261

Abstract

(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 Ptn−/− mice either fed with standard-chow diet or with HFD and in their corresponding Ptn+/+ counterparts. (3) Results: HFD-Ptn−/− 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-Ptn−/− mice showed higher UCP-1 expression in brown AT. Moreover, Ptn 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: Ptn 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.

Highlights

Obesity is a chronic disease associated with the regulation of both lipidic and glycemic metabolism and is defined by a body mass index (BMI) > 30 kg/m2 [1]
Recent studies have indicated that the increased metabolic activity of brown adipose tissue (BAT) may represent a novel therapeutical approach to prevent the development of nonalcoholic fatty liver disease (NAFLD) [5,6] and to reduce circulating lipids [7] due to the metabolic crosstalk between liver and BAT [8]
We provide evidence that Ptn deletion protects against the development of high-fat diet (HFD)-induced insulin resistance and liver steatosis, by increasing UCP-1 expression in BAT and inducing periovarian adipose tissue browning

Summary

Introduction

Obesity is a chronic disease associated with the regulation of both lipidic and glycemic metabolism and is defined by a body mass index (BMI) > 30 kg/m2 [1]. A high-fat diet, usually observed in obesity, increases the risk of developing primary hepatic steatosis, as overnutrition and lack of exercise cause the liver and other tissues to store the excess of energy as a short-term protective mechanism [2,3]. This protective mechanism in the liver is long-term associated with the development of NAFLD [4]. In the last decade, several studies have highlighted the emergence of brown adipocytes in the white adipose depots in response to exercise [9], cold exposure [10], dietary factors [11] and cytokines or pharmaceuticals [12,13]; these brown cells within white adipose tissue can contribute to increase energy expenditure and improve metabolic health

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