Adiponectin and its receptors in non-alcoholic steatohepatitis

Published on Jan 1, 2005in Gut17.94
· DOI :10.1136/gut.2003.037010
Susanne Kaser30
Estimated H-index: 30
Alexander R. Moschen41
Estimated H-index: 41
+ 6 AuthorsHerbert Tilg71
Estimated H-index: 71
Background: Adiponectin, an adipocyte derived polypeptide, has been shown to alleviate steatosis and inflammation in mice with non-alcoholic fatty liver disease. Aim: In the present study, we wished to define liver expression of adiponectin and its receptors in morbidly obese patients undergoing bariatric surgery. Patients with non-alcoholic steatohepatitis (NASH) or simple steatosis were investigated to test whether dysregulation of this system might be involved in these disorders. Patients and methods: Liver mRNA expression of adiponectin and its recently cloned receptors RI and RII (adipoRI and adipoRII) were analysed by fluorescence based real time polymerase chain reaction in 13 patients with NASH and nine with simple steatosis. Adiponectin and adipoRII protein expression were assessed by immunohistochemistry in a subgroup of patients. Results: Adiponectin and adipoRII mRNA expression were significantly reduced in liver biopsies of patients with NASH compared with simple steatosis while no difference was found in adipoRI mRNA expression. In NASH, adipoRII mRNA expression was negatively correlated with serum aspartate aminotransferase levels, serum alanine aminotransferase levels, and grade of fibrosis. Liver adiponectin protein expression was mainly found in endothelial cells of portal vessels and liver sinusoids whereas adipoRII expression was seen in hepatocytes only. Adiponectin and adipoRII staining were lower in biopsies of subjects with NASH compared with simple steatosis. Conclusion: Reduced hepatic expression of adiponectin and adipoRII might be of pathophysiological relevance in non-alcoholic fatty liver diseases.
  • References (16)
  • Citations (331)
Published on May 1, 2004in Diabetologia7.11
Cyrille Debard23
Estimated H-index: 23
Martine Laville49
Estimated H-index: 49
+ 5 AuthorsHubert Vidal69
Estimated H-index: 69
Aims/hypothesis Defective oxidation of long-chain fatty acids is a feature of insulin resistance and Type 2 diabetes. Our aim was to compare the expression levels of the genes encoding the major proteins and enzymes of this pathway in skeletal muscle of healthy subjects and Type 2 diabetic patients.
Published on Oct 1, 2003in Hepatology14.97
Brent A. Neuschwander-Tetri3
Estimated H-index: 3
(SLU: Saint Louis University),
Elizabeth M. Brunt71
Estimated H-index: 71
(SLU: Saint Louis University)
+ 2 AuthorsBruce R. Bacon69
Estimated H-index: 69
(SLU: Saint Louis University)
Insulin resistance (IR) commonly is associated with nonalcoholic steatohepatitis (NASH). To establish whether IR causes NASH, this study was undertaken to determine if improving IR would improve the histologic features that define NASH. Thirty adults with prior biopsy evidence of NASH were enrolled to receive rosiglitazone, 4 mg twice daily for 48 weeks. All patients were overweight (body mass index [BMI] > 25 kg/m2) and 23% were severely obese (BMI > 35 kg/m2); 50% had impaired glucose toleranc...
Published on Jul 1, 2003in Journal of Clinical Investigation12.28
Aimin Xu68
Estimated H-index: 68
(University of Auckland),
Yu Wang54
Estimated H-index: 54
(University of Auckland)
+ 3 AuthorsGarth J. S. Cooper56
Estimated H-index: 56
(University of Auckland)
Adiponectin has recently been shown to be a promising candidate for the treatment of obesity-associated metabolic syndromes. Replenishment of recombinant adiponectin in mice can decrease hyperglycemia, reverse insulin resistance, and cause sustained weight loss without affecting food intake. Here we report its potential roles in alcoholic and nonalcoholic fatty liver diseases in mice. Circulating concentrations of adiponectin decreased significantly following chronic consumption of high-fat etha...
Published on Jul 1, 2003in Diabetes7.20
Masanori Iwaki5
Estimated H-index: 5
Morihiro Matsuda45
Estimated H-index: 45
+ 4 AuthorsIichiro Shimomura9
Estimated H-index: 9
Adiponectin is a fat-derived hormone with antidiabetic and antiatherogenic properties. Hypoadiponectinemia seen in obesity is associated with insulin-resistant diabetes and atherosclerosis. Thiazolidinediones, peroxisome proliferator-activated receptor-γ (PPAR-γ) agonists, have been shown to increase plasma adiponectin levels by the transcriptional induction in adipose tissues. However, the precise mechanism of such action is unknown. In this study, we have identified a functional PPAR-responsiv...
Published on Jun 1, 2003in Nature43.07
Toshimasa Yamauchi62
Estimated H-index: 62
(UTokyo: University of Tokyo),
Junji Kamon19
Estimated H-index: 19
(UTokyo: University of Tokyo)
+ 23 AuthorsTakashi Kadowaki121
Estimated H-index: 121
(UTokyo: University of Tokyo)
Corrigendum (2004) Adiponectin (also known as 30-kDa adipocyte complement-related protein; Acrp30)1,2,3,4 is a hormone secreted by adipocytes that acts as an antidiabetic5,6,7,8,9,10,11,12 and anti-atherogenic8,12,13 adipokine. Levels of adiponectin in the blood are decreased under conditions of obesity, insulin resistance and type 2 diabetes2. Administration of adiponectin causes glucose-lowering effects and ameliorates insulin resistance in mice5,6,7. Conversely, adiponectin-deficient mice exh...
Published on May 1, 2003in Diabetes7.20
Fredrik Pellmé4
Estimated H-index: 4
Ulf Smith83
Estimated H-index: 83
+ 5 AuthorsPer-Anders Jansson42
Estimated H-index: 42
Adiponectin, one of the most abundant gene transcript proteins in human fat cells, has been shown to improve insulin action and is also suggested to exert antiatherogenic effects. We measured circulating adiponectin levels and risk factors for atherosclerosis in 45 healthy first-degree relatives of type 2 diabetic subjects (FDR) as well as 40 healthy control subjects (CON) without a known family history of diabetes. Insulin sensitivity ( S i ) was studied with the minimal model, and measurements...
Published on Feb 1, 2003in Diabetes7.20
Otto Tschritter32
Estimated H-index: 32
Andreas Fritsche71
Estimated H-index: 71
+ 7 AuthorsMichael Stumvoll85
Estimated H-index: 85
In animals, the adipocyte-derived hormone adiponectin has been shown to improve insulin sensitivity, a key factor in the pathogenesis of type 2 diabetes. In Pima Indians, high plasma adiponectin levels are associated with increased insulin sensitivity and reduced risk of type 2 diabetes. It is unclear whether this is also the case in white individuals and whether an additional beneficial effect on lipid metabolism exists. We therefore analyzed in nondiabetic individuals the associations between ...
Published on Mar 1, 2002in Trends in Endocrinology and Metabolism9.78
Anders H Berg A H31
Estimated H-index: 31
(Yeshiva University),
Terry P. Combs26
Estimated H-index: 26
(Yeshiva University),
Philipp E. Scherer111
Estimated H-index: 111
(Albert Einstein College of Medicine)
In recent years, we have learned that adipocytes are not merely inert storage depots for triglycerides but rather highly active cells with potent autocrine, paracrine and endocrine functions. Adipose tissue secretes a large number of physiologically active polypeptides. Although leptin remains one of the best-studied examples of an adipocyte-specific secretory factor, recent reports describe potent physiological activities for another adipocyte-specific secreted protein, adipocyte complement-rel...
Published on Jan 1, 2002in Trends in Endocrinology and Metabolism9.78
Claire M. Steppan21
Estimated H-index: 21
(UPenn: University of Pennsylvania),
Mitchell A. Lazar113
Estimated H-index: 113
(UPenn: University of Pennsylvania)
Abstract Obesity is a major risk factor for insulin resistance and type 2 diabetes mellitus. Adipocytes secrete numerous substances that might contribute to peripheral insulin sensitivity. These include leptin, tumor necrosis factor α, Acrp30/adiponectin/adipoQ and interleukin 6, the potential roles of which are briefly reviewed here. Thiazolidinedione (TZD) antidiabetic drugs regulate gene transcription by binding to peroxisome proliferator activated receptor γ, a nuclear hormone receptor found...
Published on Dec 1, 2001in Hepatology14.97
Javier Crespo30
Estimated H-index: 30
A. Cayon8
Estimated H-index: 8
+ 5 AuthorsF. Pons-Romero22
Estimated H-index: 22
The main objective of this study was to analyze the pathogenic role of the tumor necrosis factor [alpha ] (TNF-[alpha ]) system in the development of nonalcoholic steatohepatitis (NASH). Fifty-two obese patients were studied. We investigated: (1) the expression of mRNA of TNF-[alpha ] and their p55 and p75-receptors by quantitative reverse-transcriptase polymerase chain reaction (RT-PCR) in hepatic and adipose tissues; and (2) the relationship between TNF-[alpha ], p55, and p75 and the severity ...
Cited By331
Published on Jul 1, 2019in Physiological Reports
Xin-Hua Liu15
Estimated H-index: 15
(ISMMS: Icahn School of Medicine at Mount Sinai),
Jiang Ping Pan + 1 AuthorsChristopher Cardozo30
Estimated H-index: 30
(ISMMS: Icahn School of Medicine at Mount Sinai)
Published on May 1, 2019in Medical Hypotheses1.32
Abstract Type-II Endometrial Cancer (EMC) is one of the most common types of gynaecological cancer affecting more than 2.7 million people worldwide. Clinical evidence shows that adipokines levels are abnormally altered in Type-II EMC and reported to be one of the major responsible factor for uncontrolled proliferation and metastasis in Type-II EMC. Reversing the altered adipokine levels, therefore, help to control Type-II EMC proliferation and metastasis. In the present hypothesis we focus on th...
Published on Apr 30, 2019in International Journal of Molecular Sciences4.18
Luca Gelsomino8
Estimated H-index: 8
Giuseppina Daniela Naimo3
Estimated H-index: 3
+ 2 AuthorsSebastiano Andò49
Estimated H-index: 49
Obesity, characterized by excess body weight, is now accepted as a hazardous health condition and an oncogenic factor. In different epidemiological studies obesity has been described as a risk factor in several malignancies. Some biological mechanisms that orchestrate obesity–cancer interaction have been discovered, although others are still not completely understood. The unbalanced secretion of biomolecules, called “adipokines”, released by adipocytes strongly influences obesity-related cancer ...
Published on Mar 1, 2019in Journal of Clinical Laboratory Analysis1.73
Hongmei Zhang7
Estimated H-index: 7
(SJTU: Shanghai Jiao Tong University),
Hongmei Zhang21
Estimated H-index: 21
(SJTU: Shanghai Jiao Tong University)
+ 6 AuthorsLi Qin8
Estimated H-index: 8
(SJTU: Shanghai Jiao Tong University)
Published on Jan 1, 2019in Cellular and Molecular Life Sciences7.01
Fernando Bessone15
Estimated H-index: 15
María Valeria Razori2
Estimated H-index: 2
Marcelo G. Roma23
Estimated H-index: 23
Nonalcoholic fatty liver disease (NAFLD) is a main hepatic manifestation of metabolic syndrome. It represents a wide spectrum of histopathological abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with or without fibrosis and, eventually, cirrhosis and hepatocellular carcinoma. While hepatic simple steatosis seems to be a rather benign manifestation of hepatic triglyceride accumulation, the buildup of highly toxic free fatty acids associated with insulin resistan...
Published on May 16, 2018in PLOS ONE2.78
Konstantin Rozenberg4
Estimated H-index: 4
(Ariel University),
Tovit Rosenzweig10
Estimated H-index: 10
(Ariel University)
Background The glucose lowering properties of Sarcopoterium spinosum, a traditional medicinal plant, were previously validated by us using KK-Ay mice as a genetic model for type 2 diabetes (T2D). Objective To clarify the effects of Sarcopoterium spinosum extract (SSE) on diet-induced glucose intolerance and to investigate SSE effects on carbohydrate and lipid metabolism in target tissues of both high-fat-diet (HFD)-fed and KK-Ay mice. Results Mice were given SSE (70 mg/day) for 6 weeks. SSE impr...
Published on May 7, 2018in Biomedicines
Tania Gamberi13
Estimated H-index: 13
Francesca Magherini16
Estimated H-index: 16
+ 1 AuthorsTania Fiaschi24
Estimated H-index: 24
In the liver, adiponectin regulates both glucose and lipid metabolism and exerts an insulin-sensitizing effect. The binding of adiponectin with its specific receptors induces the activation of a proper signaling cascade that becomes altered in liver pathologies. This review describes the different signaling pathways in healthy and diseased hepatocytes, also highlighting the beneficial role of adiponectin in autophagy activation and hepatic regeneration.
Published on May 1, 2018in American Journal of Men's Health
Uriel A. López-Lemus2
Estimated H-index: 2
(University of Colima),
Raquel Garza-Guajardo7
Estimated H-index: 7
(Universidad Autónoma de Nuevo León)
+ 12 AuthorsMargarita L. Martinez-Fierro10
Estimated H-index: 10
(UAZ: Autonomous University of Zacatecas)
Metabolic syndrome (MS) has been associated with testicular damage. Nonalcoholic fatty liver disease (NAFLD) is a multisystemic disease that affects different organs, but its effect on the testes is unknown. A study analyzing germ cell involvement on BALB/c mice was carried out. A parallel comparative study was conducted that investigated alterations in the germinal epithelium of male humans that died from an unrelated acute event. The complete medical histories and histologic samples of the tho...
Published on Apr 1, 2018in Molecular Nutrition & Food Research4.65
Cheng Chung Li1
Estimated H-index: 1
(Tufts University),
Chun Liu22
Estimated H-index: 22
(Tufts University)
+ 7 AuthorsXiang-Dong Wang36
Estimated H-index: 36
(Tufts University)
One of the consequences of the obesity epidemic is an increased prevalence of nonalcoholic fatty liver disease (NAFLD). This study demonstrates that dietary TP effectively inhibits high fat diet (HFD)‐induced NAFLD independent of carotenoid cleavage enzymes.