Selective purification and characterization of adiponectin multimer species from human plasma

Hada, Yusuke; Yamauchi, Toshimasa; Waki, Hironori; Tsuchida, Atsushi; Hara, Kazuo; Yago, Hirokazu; Miyazaki, Osamu; Ebinuma, Hiroyuki; Kadowaki, Takashi

doi:10.1016/j.bbrc.2007.03.004

Cited by 132 publications

(88 citation statements)

References 25 publications

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“…[8][9][10][11] Moreover, human adiponectin mutation analysis 20 led to the identification of HMW adiponectin as the most active form. 21 We then developed an enzyme-linked immunosorbent assay system and showed that measurement of HMW is useful for the prediction of insulin resistance and metabolic syndrome. 24 Recently, we showed that adiponectin also centrally regulates energy expenditure and food intake.…”

Section: Discussionmentioning

confidence: 99%

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Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases

2008

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Adiponectin and adiponectin receptors (AdipoRs) have been found to play significant roles in the etiology of obesity-related chronic disease. Their discovery has been a long and complicated path, with many challenges. Developing methods to unravel the molecular secrets has been an informative process in itself. However, with both functional and genetic studies confirming adiponectin as a therapeutic target adipokine, many roles and interactions with certain other biomolecules have been clearly defined. We have found that decreased high molecular weight (HMW) adiponectin plays a crucial and causal role in obesitylinked insulin resistance and metabolic syndrome; that AdipoR1 and AdipoR2 serve as the major AdipoRs in vivo; and that AdipoR1 activates the AMP kinase (AMPK) pathway and AdipoR2, the peroxisome proliferator-activated receptor alpha (PPARa) pathway in the liver, to increase insulin sensitivity and decrease inflammation. Further conclusions are that decreased adiponectin action and increased monocyte chemoattractant protein-1 (MCP-1) form a vicious adipokine network causing obesity-linked insulin resistance and metabolic syndrome; PPARg upregulates HMW adiponectin and PPARa upregulates AdipoRs; that dietary osmotin can serve as a naturally occurring adiponectin receptor agonist; and finally, that under starvation conditions, MMW adiponectin activates AMPK in hypothalamus, and promotes food intake, and at the same time HMW adiponectin activates AMPK in peripheral tissues, such as skeletal muscle, and stimulates fatty-acids combustion. Importantly, under pathophysiological conditions, such as obesity and diabetes, only HMW adiponectin was decreased; therefore, strategies to increase only HMW adiponectin may be a logical approach to provide a novel treatment modality for obesity-linked diseases, such as insulin resistance and type 2 diabetes. It is hoped that these data will be helpful in developing treatments to counteract the destructive, expensive and painful effects of obesity.

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Section: Discussionmentioning

confidence: 99%

“…Indeed, HMW adiponectin from human plasma had the highest binding activity to the membrane fraction of C2C12 myocytes, and activated AMPK most potently 21 (Figure 4).…”

Section: High Molecular Weight (Hmw) Adiponectin As a Novel Biomarkermentioning

confidence: 99%

Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases

2008

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“…Adiponectin activates AMPK and stimulates fatty acid oxidation and glucose uptake in skeletal muscle (500, 561) and adipose tissue (554). Purification and characterization of adiponectin multimers from human plasma suggest that highmolecular-weight adiponectin most potently stimulates AMPK activity, at least in C2C12 cells (178). The activation of AMPK signaling is dependent on signaling through the adiponectin receptor 1 (AdipoR1) (563) and requires the adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPL1); however, it is still unknown how AAPL1 regulates AMPK signaling (312).…”

Section: Adiponectinmentioning

confidence: 99%

AMPK in Health and Disease

Steinberg¹,

Kemp²

2009

Physiological Reviews

1,418

1,404

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The function and survival of all organisms is dependent on the dynamic control of energy metabolism, when energy demand is matched to energy supply. The AMP-activated protein kinase (AMPK) αβγ heterotrimer has emerged as an important integrator of signals that control energy balance through the regulation of multiple biochemical pathways in all eukaryotes. In this review, we begin with the discovery of the AMPK family and discuss the recent structural studies that have revealed the molecular basis for AMP binding to the enzyme's γ subunit. AMPK's regulation involves autoinhibitory features and phosphorylation of both the catalytic α subunit and the β-targeting subunit. We review the role of AMPK at the cellular level through examination of its many substrates and discuss how it controls cellular energy balance. We look at how AMPK integrates stress responses such as exercise as well as nutrient and hormonal signals to control food intake, energy expenditure, and substrate utilization at the whole body level. Lastly, we review the possible role of AMPK in multiple common diseases and the role of the new age of drugs targeting AMPK signaling.

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“…Adiponectin is a 244-amino acid-long polypeptide that circulates as homotrimers, low-molecular-weight (LMW) oligomers, and high-molecular-weight (HMW) complexes (25). It has been suggested that the HMW adiponectin complex is the major source of the active form (47), representing ϳ70% of circulating adiponectin in healthy subjects (42).…”

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confidence: 99%

Transcriptome profiling in response to adiponectin in human cancer-derived cells

Berger

Rome

Véga

et al. 2010

Physiological Genomics

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The adipocyte-derived hormone adiponectin exerts protective actions in several disorders, including some cancers. However, while growing data suggest that adiponectin could be an effective anticancer agent, its mechanism of action in cancer cells is still poorly known. Here, using microarrays, we identified a set of 1,301 genes commonly modulated in three cancer-derived cell lines in response to short-term stimulation with full-length recombinant human adiponectin. Most of these genes are involved in translation regulation, immune or stress responses, and cell proliferation. Furthermore, among genes linked to disease that were retrieved by functional enrichment tests using text mining based on PubMed analysis, we found that 66% are involved in malignant neoplasms, further supporting the link between adiponectin and cancer mechanisms. Bioinformatic analysis demonstrated the diversity of signaling pathways and transcription factors potentially mediating adiponectin effects on gene expression, illustrating the complexity of adiponectin mechanisms of action in cancer cells.

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Selective purification and characterization of adiponectin multimer species from human plasma

Cited by 132 publications

References 25 publications

Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases

Physiological and pathophysiological roles of adiponectin and adiponectin receptors in the integrated regulation of metabolic and cardiovascular diseases

AMPK in Health and Disease

Transcriptome profiling in response to adiponectin in human cancer-derived cells

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