Expression of adiponectin and its receptors in livers of morbidly obese patients with non‐alcoholic fatty liver disease

Ma, Hong; Gómez, Victoria; Lü, Liang; Yang, Xiao; Wu, Xiaoyan; Xiao, Shu Yuan

doi:10.1111/j.1440-1746.2008.05548.x

Cited by 70 publications

(48 citation statements)

References 25 publications

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“…This leads us to hypothesize the existence of proteins with reductase activity acting on adiponectin multimeric isoforms. Another plausible hypothesis on adiponectin distribution in plasma is that the subcutaneous AT secretes primarily HMW adiponectin and MMW and LMW isoforms in plasma can proceed from different sources other than the AT itself (42)(43)(44)(45). The differences between adiponectin production in subcutaneous and visceral fat depot may also contribute to the above-mentioned differences between secretion in subcutaneous AT and plasma as both fat depots contribute to the circulating levels of adiponectin.…”

Section: Discussionmentioning

confidence: 99%

Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

Kováčová

Vítková

Kováčiková

et al. 2009

European Journal of Endocrinology

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Objective: Adiponectin is a protein abundantly secreted by the adipose tissue (AT). Plasma adiponectin levels are decreased in obese, insulin-resistant, and type 2 diabetic patients. Various multimeric complexes, i.e. high-, middle-, and low-molecular weight isoforms (HMW, MMW and LMW), are present in plasma. Here, we investigated the effect of weight reducing diet on the distribution of adiponectin isoforms in plasma and on their secretion in AT explants from obese subjects. Design: A total of 20 obese subjects (age 37.8G7.3 years, body mass index 33.9G5.0 kg/m 2 ) underwent eight weeks of very low-calorie diet (VLCD). A needle biopsy of subcutaneous abdominal AT and blood samples were taken before and after dietary intervention. AT explants were incubated in culture medium for 4 h. ELISA assay and western blot analyses were used to identify adiponectin complexes in culture media and in plasma. Results: The distribution of adiponectin polymers in plasma was different from that secreted in human AT explants. Before VLCD, the relative amount of HMW isoform was 75.5G9.1% of total adiponectin in culture media and 52.2G11.2% in plasma. Despite the diet-induced weight loss and improvement of insulin sensitivity, VLCD neither induced change in total adiponectin level nor in the ratio of HMW to total adiponectin in plasma and in culture media of AT explants. Conclusions: The profile of adiponectin polymeric isoforms secreted by AT explants into culture media differs from the plasma profile. A dietary intervention leading to weight loss and improvement of insulin sensitivity was not associated with modifications of AT secretion of total or HMW adiponectin.

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Section: Discussionmentioning

confidence: 99%

Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

Kováčová

Vítková

Kováčiková

et al. 2009

European Journal of Endocrinology

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“…Except for adiponectin, its liver-specific R2 receptor (AdipoR2) appears to play a role in steatosis and inflammation. At the cellular/molecular level AdipoR2 mRNA was reduced in liver samples of patients with NASH [95,96] . It was suggested that AdipoR2 may be protective against steatosis-related hepatic insulin resistance [97] .…”

Section: Mechanistic Implicationsmentioning

confidence: 99%

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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“…4 Adiponectin has been suggested to play an important role in the pathogenesis of liver fibrosis. [7][8][9][10][11][12][13][14][15] Notably, in addition to adipose tissue, adiponectin is expressed in stellate cells. 16 Previous studies have shown that adiponectin has important effects specifically on stellate cells, and the mechanism of these effects remains an area of active investigation.…”

mentioning

confidence: 99%

Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

Shafiei

Shetty

Scherer

et al. 2011

The American Journal of Pathology

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In this study, we elucidated the mechanism by which adiponectin modulates hepatic stellate cell activation and fibrogenesis. Adiponectin-overexpressing transgenic mice receiving thioacetamide were resistant to fibrosis, compared with controls. In contrast, adiponectin-null animals developed severe fibrosis. Expression of collagen ␣1(I) and ␣-smooth muscle actin (␣-SMA) mRNAs were significantly lower in adiponectin-overexpressing mice, compared with controls. In wild-type stellate cells exposed to a lentivirus encoding adiponectin, expression of peroxisome proliferator-activated receptor-␥ (PPAR␥), SREBP1c, and CEBP␣ mRNAs was significantly increased (3.2-, 4.1-, and 2.2-fold, respectively; n ‫؍‬ 3; P < 0.05, adiponectin virus versus control), consistent with possible activation of an adipogenic transcriptional program. Troglitazone, a PPAR␥ agonist, strongly suppressed upregulation of collagen ␣1(I) and ␣-SMA mRNA in stellate cells isolated from wild-type mice; however, stellate cells from adiponectin-null animals failed to respond to troglitazone. Furthermore, in isolated stellate cells in which PPAR␥ was depleted using an adenovirus-Cre-recombinase system and in which adiponectin was also overexpressed, collagen ␣1(I) and ␣-SMA were significantly inhibited. We conclude that the PPAR␥ effect on stellate cell activation and the fibrogenic cascade appears to be adiponectin-dependent; however, the inhibitory effect of adiponectin on stellate cell activation was not dependent on PPAR␥, suggesting the presence of PPAR␥-dependent as well as independent pathways in stellate cells.

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Expression of adiponectin and its receptors in livers of morbidly obese patients with non‐alcoholic fatty liver disease

Abstract: These findings indicate that decreased liver adiponectin expression may play a role in the development and progression of NAFLD, from simple steatosis to NASH, in morbidly obese patients.

Cited by 70 publications

References 25 publications

Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

Secretion of adiponectin multimeric complexes from adipose tissue explants is not modified by very low calorie diet

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

Adiponectin Regulation of Stellate Cell Activation via PPARγ-Dependent and -Independent Mechanisms

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