Role of Meltrin α (ADAM12) in Obesity Induced by High- Fat Diet

Masaki, Megumi; Kurisaki, Tomohiro; Shirakawa, Kamon; Sehara-Fujisawa, Atsuko

doi:10.1210/en.2004-1082

Cited by 45 publications

(38 citation statements)

References 37 publications

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“…Meltrin alpha (Adam12) is a metalloprotease-disintegrin that belongs to the ADAM (for “a disintegrin and metalloprotease”) family. Compared with wild-type mice, meltrin alpha(-/-) mice displayed moderate resistance to weight gain induced by a high-fat diet, mainly because of an increase in the number of adipocytes [24]. Another QTL is significantly associated with mouse liver weight after 8 weeks on an atherogenic diet (-log(P) = 8.2) and is located on chromosome 18, spanning less than 100 kb, where Cdh2 is the only candidate gene ( Figure 5B ).…”

Section: Resultsmentioning

confidence: 99%

Large-Scale In Silico Mapping of Complex Quantitative Traits in Inbred Mice

Liu¹,

Vikis²,

Lü³

et al. 2007

PLoS ONE

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Understanding the genetic basis of common disease and disease-related quantitative traits will aid in the development of diagnostics and therapeutics. The processs of gene discovery can be sped up by rapid and effective integration of well-defined mouse genome and phenome data resources. We describe here an in silico gene-discovery strategy through genome-wide association (GWA) scans in inbred mice with a wide range of genetic variation. We identified 937 quantitative trait loci (QTLs) from a survey of 173 mouse phenotypes, which include models of human disease (atherosclerosis, cardiovascular disease, cancer and obesity) as well as behavioral, hematological, immunological, metabolic, and neurological traits. 67% of QTLs were refined into genomic regions <0.5 Mb with ∼40-fold increase in mapping precision as compared with classical linkage analysis. This makes for more efficient identification of the genes that underlie disease. We have identified two QTL genes, Adam12 and Cdh2, as causal genetic variants for atherogenic diet-induced obesity. Our findings demonstrate that GWA analysis in mice has the potential to resolve multiple tightly linked QTLs and achieve single-gene resolution. These high-resolution QTL data can serve as a primary resource for positional cloning and gene identification in the research community.

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Section: Resultsmentioning

confidence: 99%

Large-Scale In Silico Mapping of Complex Quantitative Traits in Inbred Mice

Liu¹,

Vikis²,

Lü³

et al. 2007

PLoS ONE

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“…Indeed, there is increasing evidence that obesity and T2D are associated with a chronic inflammatory state and the important role of metalloproteinases in this inflammatory paradigm is being increasingly recognized [9,28,29]. We have previously documented several mechanisms by which the metalloproteinase and disintegrin domains of ADAM28 may promote inflammation and ultimately metabolic dysfunction [9].…”

Section: Discussionmentioning

confidence: 99%

The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice

Herat

Rudnicka

Okada

et al. 2017

IJMS

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Obesity and diabetes are major causes of morbidity and mortality globally. The current study builds upon our previous association studies highlighting that A Disintegrin And Metalloproteinase 28 (ADAM28) appears to be implicated in the pathogenesis of obesity and type 2 diabetes in humans. Our novel study characterised the expression of ADAM28 in mice with the metabolic syndrome and used molecular inhibition approaches to investigate the functional role of ADAM28 in the pathogenesis of high fat diet-induced obesity. We identified that ADAM28 mRNA and protein expression was markedly increased in the livers of mice with the metabolic syndrome. In addition, noradrenaline, the major neurotransmitter of the sympathetic nervous system, results in elevated Adam28 mRNA expression in human monocytes. Downregulation of ADAM28 with siRNA technology resulted in a lack of weight gain, promotion of insulin sensitivity/glucose tolerance and decreased liver tumour necrosis factor-α (TNF-α) levels in our diet-induced obesity mouse model as well as reduced blood urea nitrogen, alkaline phosphatase and aspartate aminotransferase. In addition, we show that ADAM28 knock-out mice also displayed reduced body weight, elevated high density lipoprotein cholesterol levels, and reductions in blood urea nitrogen, alkaline phosphatase, and aspartate aminotransferase. The results of this study provide important insights into the pathogenic role of the metalloproteinase ADAM28 in the metabolic syndrome and suggests that downregulation of ADAM28 may be a potential therapeutic strategy in the metabolic syndrome.

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“…The complex but conserved structure of ADAM family members endows these proteins with various abilities leading to their key contribution to various physiological functions such as, for instance, fertilization [15,32], neurogenesis [33], adipogenesis [34,35] and myogenesis [36]. ADAMs and ADAMTSs are involved in a complex molecular network of reciprocal interactions.…”

Section: Implication Of Adams and Adamtss In Physiology And Pathologymentioning

confidence: 99%

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

et al. 2008

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A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions.

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Role of Meltrin α (ADAM12) in Obesity Induced by High- Fat Diet

Cited by 45 publications

References 37 publications

Large-Scale In Silico Mapping of Complex Quantitative Traits in Inbred Mice

Large-Scale In Silico Mapping of Complex Quantitative Traits in Inbred Mice

The Metalloproteinase ADAM28 Promotes Metabolic Dysfunction in Mice

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

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