scholarly journals Myeloid Heme Oxygenase-1 Haploinsufficiency Reduces High Fat Diet-Induced Insulin Resistance by Affecting Adipose Macrophage Infiltration in Mice

PLoS ONE ◽  
2012 ◽  
Vol 7 (6) ◽  
pp. e38626 ◽  
Author(s):  
Jun-Yuan Huang ◽  
Ming-Tsai Chiang ◽  
Shaw-Fang Yet ◽  
Lee-Young Chau
2014 ◽  
Vol 92 (10) ◽  
pp. 805-812 ◽  
Author(s):  
Yıldız Öner-İyidoğan ◽  
Sevda Tanrıkulu-Küçük ◽  
Muhammed Seyithanoğlu ◽  
Hikmet Koçak ◽  
Semra Doğru-Abbasoğlu ◽  
...  

High fat diet (HFD) is associated with oxidative stress induced fatty liver. Curcumin, an extract of Curcuma longa, has been shown to possess potent antioxidant and hypolipidemic properties. In this study, we investigated the effect of curcumin treatment on hepatic heme oxygenase-1 (HO-1) expression along with pro-oxidant–antioxidant status and lipid accumulation in rats fed an HFD. Male Sprague–Dawley rats were distributed among 4 groups: Group 1, which was fed the control diet (10% of total calories from fat); Group 2, which was fed the HFD (60% of total calories from fat); and groups 3 and 4, which received the HFD supplemented with curcumin and the control diet supplemented with curcumin (1 g/kg diet; w/w), respectively, for 16 weeks. HFD caused increases in hepatic lipid levels, production of reactive oxygen species, and lipid peroxidation. Further, HO-1 expression was significantly decreased. Histopathological examination showed hepatic fat accumulation and slight fibrotic changes. Curcumin treatment reduced hepatic lipids and oxidative stress parameters, and HO-1 expression was significantly increased. These findings suggest that increased HO-1 expression, along with suppressed oxidative stress as well as reduced hepatic fat accumulation and fibrotic changes, contribute to the beneficial effects of curcumin in attenuating the pathogenesis of fatty liver induced metabolic diseases.


2017 ◽  
Vol 87 ◽  
pp. 375-380 ◽  
Author(s):  
Tomasz Szkudelski ◽  
Kamila Dłużewicz ◽  
Jan Sadoch ◽  
Katarzyna Szkudelska

2021 ◽  
Author(s):  
Jiyoon Ryu ◽  
Jason T. Hadley ◽  
Zhi Li ◽  
Feng Dong ◽  
Huan Xu ◽  
...  

Adiponectin is an adipokine that exerts insulin sensitizing and anti-inflammatory roles in insulin target tissues including liver. While the insulin sensitizing function of adiponectin has been extensively investigated, the precise mechanism by which adiponectin alleviates diet-induced hepatic inflammation remains elusive. Here, we report that hepatocyte-specific knockout of the adaptor protein APPL2 enhanced adiponectin sensitivity and prevented mice from high fat diet-induced inflammation, insulin resistance, and glucose intolerance, although it caused fatty liver. The improved anti-inflammatory and insulin sensitizing effects in the APPL2 hepatocyte-specific knockout mice were largely reversed by knocking out adiponectin. Mechanistically, hepatocyte APPL2 deficiency enhances adiponectin signaling in the liver, which blocks TNF-a-stimulated MCP-1 expression via inhibiting the mTORC1 signaling pathway, leading to reduced macrophage infiltration and thus reduced inflammation in the liver. Taken together, our study uncovers a mechanism underlying the anti-inflammatory role of adiponectin in the liver and reveals the hepatic APPL2-mTORC1-MCP-1 axis as a potential target for treating overnutrition-induced inflammation in the liver.


2021 ◽  
Author(s):  
Jiyoon Ryu ◽  
Jason T. Hadley ◽  
Zhi Li ◽  
Feng Dong ◽  
Huan Xu ◽  
...  

Adiponectin is an adipokine that exerts insulin sensitizing and anti-inflammatory roles in insulin target tissues including liver. While the insulin sensitizing function of adiponectin has been extensively investigated, the precise mechanism by which adiponectin alleviates diet-induced hepatic inflammation remains elusive. Here, we report that hepatocyte-specific knockout of the adaptor protein APPL2 enhanced adiponectin sensitivity and prevented mice from high fat diet-induced inflammation, insulin resistance, and glucose intolerance, although it caused fatty liver. The improved anti-inflammatory and insulin sensitizing effects in the APPL2 hepatocyte-specific knockout mice were largely reversed by knocking out adiponectin. Mechanistically, hepatocyte APPL2 deficiency enhances adiponectin signaling in the liver, which blocks TNF-a-stimulated MCP-1 expression via inhibiting the mTORC1 signaling pathway, leading to reduced macrophage infiltration and thus reduced inflammation in the liver. Taken together, our study uncovers a mechanism underlying the anti-inflammatory role of adiponectin in the liver and reveals the hepatic APPL2-mTORC1-MCP-1 axis as a potential target for treating overnutrition-induced inflammation in the liver.


2016 ◽  
Author(s):  
Ann-Kristin Picke ◽  
Lykke Sylow ◽  
Lisbeth L V Moller ◽  
Rasmus Kjobsted ◽  
Erik Richter ◽  
...  

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