Osmotin Is a Homolog of Mammalian Adiponectin and Controls Apoptosis in Yeast through a Homolog of Mammalian Adiponectin Receptor

Narasimhan, Meena L.; Coca, María; Jin, Jingbo; Yamauchi, Toshimasa; Ito, Yusuke; Kadowaki, Takashi; Kim, Kyeong Kyu; Pardo, José Manuel; Damsz, Barbara; Hasegawa, Paul M.; Yun, Dae‐Jin; Bressan, Ray A.

doi:10.1016/j.molcel.2005.02.007

Cited by 32 publications

(61 citation statements)

References 35 publications

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“…For example, osmotin is a tobacco PR-5 family protein and the homolog of adiponectin. This protein has a three-dimensionally overlapping domain with adiponectin, and activate AMP kinases via adiponectin receptors [16]. We also found that the extracellular domain of feline AD-R1 was almost identical to that of human AD-R1, suggesting that the AD-R1 agonists for human diabetes medication would also be effective for the cat.…”

Section: Discussionmentioning

confidence: 60%

Feline Adiponectin: Molecular Structures and Plasma Concentrations in Obese Cats

et al. 2009

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ABSTRACT. Adiponectin is an adipokine that is specifically expressed in adipose tissues, directly sensitizes the body to insulin via specific receptors and its decreased plasma concentration is responsible for insulin resistance in obese humans. Diabetes is an important problem also in veterinary medicine, and feline diabetes is very similar to human type 2 diabetes, in which obesity is an important risk factor. In the present study, We obtained cDNA clones corresponding to feline adiponectin and adiponectin receptor 1 (AD-R1), whose nucleotide and deduced amino acid sequences were highly identical to those of other species, especially, the extra-cellular domain of feline AD-R1 was almost identical to that of human AD-R1. Adiponectin mRNA was exclusively detected in the adipose tissue, but AD-R1 was in all tissues tested in this study. Next, plasma samples were collected from 22 cats visiting veterinary practices. They were divided to 2 groups based on a five-point scale body condition score (BCS), such as normal group (BCS ranged from 2.5 through 3.5) and obese group (BCS ranged from 4.0 through 5.0). Plasma adiponectin in obese cats (7.2 ± 1.5 µg/ml) was significantly lower than that of normal cats (18.0 ± 3.2 µg/ml). These results suggest that adiponectin may be responsible for insulin function also in the cat, and it can be a target molecule for treatment of obesity and diabetes in cats. KEY WORDS: adiponectin, AD-R1, diabetes, feline, obesity.J. Vet. Med. Sci. 71(2): 189-194, 2009 The adipose tissue has long been thought to be the site for energy storage and a target of various hormones, which regulate energy metabolism. However, recent studies have revealed that the adipose tissue itself is an active endocrine organ, which produces and secretes many polypeptides, collectively called as adipokines, such as leptin, tumor necrosis factor (TNF)-α, plasminogen activator inhibitor-1 and resistin [1]. For example, leptin is secreted from adipose tissues in response to changes in energy balance, acts on hypothalamus to regulate food intake and the neuroendocrine mechanisms controlling energy expenditure [4]. Adiponectin is an adipokine found at almost three-order higher concentrations in blood than other adipokines [6], and its plasma concentration decreases with body fat accumulation [2]. It is now recognized as one of the key adipokines responsible for obesity-associated atherosclerosis and insulin resistance (diabetes mellitus of type 2) in humans [2,3]. Recently, two isoforms of adiponectin receptors (AD-R1 and AD-R2) were determined by expression cloning, and they showed different tissue distributions. AD-R1 is expressed ubiquitously in most organs including skeletal muscle, and thought to be important to keep the insulin sensitivity. In obese people, it is suggested that reduced adiponectin induces insulin resistance, and it is the major pathophysiological factor of diabetes [12,21].In companion animal medicine, as in human medicine, obesity and diabetes mellitus are the most common nutritional/endocrinol...

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Section: Discussionmentioning

confidence: 60%

Feline Adiponectin: Molecular Structures and Plasma Concentrations in Obese Cats

et al. 2009

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“…More importantly, suppression of AdipoRs expression by siRNA markedly reduced phosphorylation of AMPK induced by osmotin. These data suggested that osmotin seemed to activate AMPK through AdipoRs in mammalian C2C12 myocytes 27 (Figure 4).…”

Section: Development Of Novel Therapeutic Strategy Targeting Adiporsmentioning

confidence: 79%

“…22 Moreover, we showed that osmotin, which is present in fruits and vegetables, activated AMPK through AdipoRs in myocytes. 27 We are now screening for low molecular compounds, and for confirming the clinical effectiveness and usefulness of HMW measurement (Figure 4). …”

Section: Discussionmentioning

confidence: 96%

“…A group at Purdue University found that the receptor for osmotin was the yeast homolog of AdipoR1 (PHO36). 27 X-ray crystallographic studies revealed that domain I of osmotin can be overlapped with globular adiponectin. These data prompted us to examine whether osmotin could activate AdipoRs in mammalian cells.…”

Section: Development Of Novel Therapeutic Strategy Targeting Adiporsmentioning

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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“…Three therapeutic strategies targeting adiponectin and its receptors have been currently contemplated to tackle the metabolic and cardiovascular abnormalities commonly linked to obesity: (i) to increase adiponectin expression in white adipose tissue and plasma adiponectin levels using PPAR␥ agonists (54), (ii) to up-regulate AdipoR expression using PPAR␣ agonists (55), and (iii) to characterize novel AdipoR agonists to counteract obesity-associated reduced adiponectin sensitivity (56). In the present study, we have demonstrated that AdipoR1 and AdipoR2 interact to form homomers and heteromers that exhibit distinct adiponectin binding affinities and intracellular signaling properties.…”

Section: Discussionmentioning

confidence: 99%

Adiponectin Receptors Form Homomers and Heteromers Exhibiting Distinct Ligand Binding and Intracellular Signaling Properties

Almabouada

Díaz‐Ruiz

Rabanal-Ruíz

et al. 2013

Journal of Biological Chemistry

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Background: Adiponectin receptors (AdipoR1 and 2) mediate the effects of adiponectin, which possesses insulin sensitizing and anti-inflammatory properties. Results: AdipoRs organize into oligomers exhibiting distinct interaction and signaling properties. Conclusion:The cellular response to adiponectin depends on the specific AdipoR repertoire. Significance: To envisage novel therapeutic strategies, the capacity of AdipoRs to form oligomeric complexes must be taken into consideration.

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Osmotin Is a Homolog of Mammalian Adiponectin and Controls Apoptosis in Yeast through a Homolog of Mammalian Adiponectin Receptor

Cited by 32 publications

References 35 publications

Feline Adiponectin: Molecular Structures and Plasma Concentrations in Obese Cats

Feline Adiponectin: Molecular Structures and Plasma Concentrations in Obese Cats

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

Adiponectin Receptors Form Homomers and Heteromers Exhibiting Distinct Ligand Binding and Intracellular Signaling Properties

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