Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro

Neumeier, Markus; Weigert, Johanna; Schäffler, Andréas; Weiss, Thomas S.; Schmidl, Christian; Büttner, R.; Bollheimer, Cornelius; Aslanidis, Charalampos; Schölmerich, Jürgen; Buechler, Christa

doi:10.1016/j.bbrc.2006.09.101

Cited by 67 publications

(54 citation statements)

References 27 publications

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“…Also, liver production and plasma levels of TNF-α may be reduced [90] . Adiponectin downregulated aldehyde oxidase 1 in vivo [91] . This enzyme produces reactive oxygen species that promote cell damage and fibrogenesis [91] .…”

Section: Mechanistic Implicationsmentioning

confidence: 99%

“…Adiponectin downregulated aldehyde oxidase 1 in vivo [91] . This enzyme produces reactive oxygen species that promote cell damage and fibrogenesis [91] . Its activity is high in obesityrelated hepatic steatosis [91] .…”

Section: Mechanistic Implicationsmentioning

confidence: 99%

“…This enzyme produces reactive oxygen species that promote cell damage and fibrogenesis [91] . Its activity is high in obesityrelated hepatic steatosis [91] . Adiponectin also inhibited hepatic fibrosis by downregulating connective tissue growth factor in vitro [92] .…”

Section: Mechanistic Implicationsmentioning

confidence: 99%

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Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

131

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Non-alcoholic fatty liver disease (NAFLD) is a common health problem with a high mortality burden due to its liver-and vascular-specific complications. It is associated with obesity, high-fat diet as well as with type 2 diabetes mellitus (T2DM) and metabolic syndrome (MetS). Impaired hepatic fatty acid (FA) turnover together with insulin resistance are key players in NAFLD pathogenesis. Peroxisome proliferator-activated receptors (PPARs) are involved in lipid and glucose metabolic pathways. The novel concept is that the activation of the PPARα subunit may protect from liver steatosis. Fenofibrate, by activating PPARα, effectively improves the atherogenic lipid profile associated with T2DM and MetS. Experimental evidence suggested various protective effects of the drug against liver steatosis. Namely, fenofibraterelated PPARα activation may enhance the expression of genes promoting hepatic FA β-oxidation. Furthermore, fenofibrate reduces hepatic insulin resistance. It also inhibits the expression of inflammatory mediators involved in non-alcoholic steatohepatitis pathogenesis. These include tumor necrosis factor-α, intercellular cell adhesion molecule-1, vascular cell adhesion molecule-1 and monocyte chemoattractant protein-1. Consequently, fenofibrate can limit hepatic macrophage infiltration. Other liver-protective effects include decreased oxidative stress and improved liver microvasculature function. Experimental studies showed that fenofibrate can limit liver steatosis associated with high-fat diet, T2DM and obesity-related insulin resistance. Few studies showed that these benefits are also relevant even in the clinical setting. However, these have certain limitations. Namely, these were uncontrolled, their sample size was small, fenofibrate was used as a part of multifactorial approach, while histological data were absent. In this context, there is a need for large prospective studies, including proper control groups and full assessment of liver histology.

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Section: Mechanistic Implicationsmentioning

confidence: 99%

Section: Mechanistic Implicationsmentioning

confidence: 99%

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Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Kostapanos

Kei²,

Elisaf³

2013

WJH

131

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“…Adiponectin and fenofibrate activate PPARα (Neumeier et al, 2006) but 0.5 μM and 1 μM fenofibrate did not reduce annexin A6 levels ( Figure 2B). Similarly, IL-6 (20 ng/ml) ( Figure 2B) and IL-8 (100, 200 and 300 ng/ml, data not shown) that are both induced by adiponectin had no effect.…”

Section: Resultsmentioning

confidence: 95%

“…Annexin A6 levels also remain unchanged in cholesterol-loaded monocytic cells (Grewal et al, 2000;Pons et al, 2001;de Diego et al, 2002;Cubells et al, 2007) further excluding that cellular cholesterol content regulates annexin A6. Beside AMPK, PPARα is also activated by adiponectin (Yamauchi et al, 2007) but a PPARα antagonist (Neumeier et al, 2006) does not inhibit adiponectin mediated suppression of annexin A6 (own unpublished observation). Therefore, the adiponectin-stimulated pathways that downregulate annexin A6 levels have still to be identified in further studies.…”

Section: Discussionmentioning

confidence: 97%

Annexin A6 is highly abundant in monocytes of obese and type 2 diabetic individuals and is downregulated by adiponectin in vitro

et al. 2009

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Adiponectin stimulates cholesterol efflux in macrophages and low adiponectin may in part contribute to disturbed reverse cholesterol transport in type 2 diabetes. Monocytes express high levels of annexin A6 that could inhibit cholesterol efflux and it was investigated whether the atheroprotective effects of adiponectin are accompanied by changes in annexin A6 levels. Adiponectin reduces annexin A6 protein whereas mRNA levels are not affected. Adiponectin-mediated activation of peroxisome proliferator-activated receptor α (PPARα) and AMP-activated protein kinase (AMPK) does not account for reduced annexin A6 expression. Further, fatty acids and lipopolysaccharide that are elevated in obesity do not influence annexin A6 protein levels. Annexin A6 in monocytes from overweight probands or type 2 diabetic patients is significantly elevated compared to monocytes of normal-weight controls. Monocytic annexin A6 positively correlates with body mass index and negatively with systemic adiponectin of the blood donors. Therefore, the current study demonstrates that adiponectin reduces annexin A6 in monocytes and thereby may enhance cholesterol efflux. In agreement with these in vitro finding an increase of monocytic annexin A6 in type 2 diabetes monocytes was observed.

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Activation of peroxisome proliferator-activated receptor-α inhibits the injurious effects of adiponectin in rat steatotic liver undergoing ischemia–reperfusion

Zaoualí²,

et al. 2008

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Aldehyde oxidase 1 is highly abundant in hepatic steatosis and is downregulated by adiponectin and fenofibric acid in hepatocytes in vitro

Cited by 67 publications

References 27 publications

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Current role of fenofibrate in the prevention and management of non-alcoholic fatty liver disease

Annexin A6 is highly abundant in monocytes of obese and type 2 diabetic individuals and is downregulated by adiponectin in vitro

Activation of peroxisome proliferator-activated receptor-α inhibits the injurious effects of adiponectin in rat steatotic liver undergoing ischemia–reperfusion

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