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

Figures

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  Figure 1. Effects of Ptn deletion and HFD feeding on body weight and periovarian and brown adipose tissue weights. (a) Body weight and increase in body weight (insert), (b) periovarian white adipose tissue weight and (c) brown adipose tissue weight of Ptn+/+ and Ptn−/− mice fed with a standard chow diet (STD) or with a high-fat diet (HFD). Data are expressed as mean ± SEM of n = 12 mice/group. * p < 0.05; ** p < 0.01 for differences in the effect of HFD feeding within Ptn+/+ or Ptn−/− mice. # p < 0.05; ### p < 0.001 for differences between Ptn+/+ and Ptn−/−.

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  Figure 2. Ptn−/− mice show reduced liver weight and altered lipid profile when fed with a high-fat diet. (a) Liver weight, (b) total hepatic lipid content, (c) hematoxylin-eosin staining of formalin-fixed paraffin embedded liver tissue sections, (d) hepatic triacylglycerides, (e) hepatic phospholipids, (f) hepatic cholesteryl esters, and (g) hepatic cholesterol of Ptn+/+ and Ptn−/− mice fed with a standard chow diet (STD) or with a high-fat diet (HFD). Data are mean ± SEM of n = 6–12 mice/group. * p < 0.05; ** p < 0.01; *** p < 0.001 for differences in the effect of HFD feeding within Ptn+/+ or Ptn−/− mice. # p < 0.05, ## p < 0.01, ### p < 0.001 for differences between Ptn+/+ versus Ptn−/−.

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  Figure 3. Circulating lipid profile and insulin sensitivity is impaired with high-fat diet and Ptn deletion after 6 h fasting. (a) Triacylglycerides, (b), cholesterol, (c) NEFA (d) glycerol, (e) glucose, (f) insulin and (g) HOMA-IR index of Ptn+/+ and Ptn−/− mice fed with a standard chow diet (STD) or with a high-fat diet (HFD). Data are mean ± SEM of n = 8–12 mice/group. *p < 0.05; ** p < 0.01; *** p < 0.001 for differences in the effect of HFD feeding within Ptn+/+ or Ptn−/− mice. # p < 0.05; ## p < 0.01 for differences between Ptn+/+ and Ptn−/−.

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  Figure 4. High-fat diet feeding and Ptn deletion effects on lipid metabolism in liver. (a) Aqp9 (aquaporin 9) mRNA, (b) Acly (ATP citrate lyase) mRNA, (c) Acc (acetyl-CoA carboxylase) mRNA, (d) Fas (fatty acid synthase) mRNA, (e) Gpat (glycerol 3-phosphate acyltransferase) mRNA, (f) Lpin2 (lipin 2) mRNA, (g) Dgat1 (diacylglycerol O-acyltransferase 1) mRNA, (h) Dgat2 (diacylglycerol O-acyltransferase 2) mRNA, and (i) Cpt1α (carnitine palmitoyl transferase 1α) mRNA in the liver of Ptn+/+ and Ptn−/− mice fed with a standard chow diet (STD) or with a high-fat diet (HFD). Data are mean ± SEM of n = 5–6 mice/group. *p < 0.05, ** p < 0.01, *** p < 0.001 for differences in the effect of HFD feeding within Ptn+/+ or Ptn−/− mice. # p < 0.05, ## p < 0.01, ### p < 0.001 for differences between Ptn+/+ and Ptn−/−.

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  Figure 5. High-fat diet and Ptn deletion effects on brown adipose tissue UCP-1. Ucp1 (uncoupling protein-1) (a) mRNA and(b) protein in brown adipose tissue of Ptn+/+ and Ptn−/− mice fed with a standard chow diet (STD) or with a high-fat diet (HFD). Data are mean ± SEM of n = 5–6 mice/group. * p < 0.05; ** p < 0.01 for differences in the effect of HFD feeding within Ptn+/+ or Ptn−/− mice. # p < 0.05 for differences between Ptn+/+ and Ptn−/−.

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  Figure 6. Deletion of pleiotrophin is associated with white adipose tissue browning. (a) Adipocyte cell size distribution from the periovarian AT of Ptn+/+ (upper histogram) and Ptn−/− mice, (bottom histogram). (b) Representative immunohistochemistry for UCP-1 in periovarian adipose tissue sections. (c) Pparγ1 (peroxisome proliferator-activated receptor-γ1) mRNA, (d) Pgc1α (peroxisome proliferator-activated receptor-γ coactivator 1-α) mRNA, (e) Cidea (cell death-inducing DNA fragmentation factor, alpha subunit-like effector A) mRNA, (f) Ucp1 (Uncoupling protein-1) mRNA in periovarian AT of Ptn+/+ and Ptn−/− mice fed with a standard chow diet (STD) or with a high-fat diet (HFD). Data are mean ± SEM of n = 4–6 mice/group. * p < 0.05, *** p < 0.001 for differences in the effect of HFD feeding within Ptn+/+ or Ptn−/− mice. # p < 0.05; ### p < 0.001 for differences between Ptn+/+ and Ptn−/−. The arrow in panel (b) indicates immunoreactivity with UCP-1 antibody.