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Adiponectin, C1Q and collagen domain containing
PDB rendering based on 1c28.
Available structures: 1c28, 1c3h
Identifiers
Symbol(s)	ADIPOQ; ACDC; ACRP30; APM-1; APM1; GBP28; adiponectin
External IDs	OMIM: 605441 MGI: 106675 HomoloGene: 3525
Gene Ontology Molecular Function: • hormone activity Cellular Component: • extracellular region • extracellular space • cytoplasm • endoplasmic reticulum Biological Process: • glucose metabolic process • generation of precursor metabolites and energy • fatty acid beta-oxidation • phosphate transport • response to glucose stimulus • glucose homeostasis • positive regulation of I-kappaB kinase/NF-kappaB cascade • negative regulation of gluconeogenesis • positive regulation of fatty acid metabolic process • positive regulation of glucose import • protein homooligomerization
RNA expression pattern
Image File history File links Question_book-3. ... For the file format that describes the 3D structures of molecules found in the Protein Data Bank, see Protein Data Bank (file format). ... Look up Hugo in Wiktionary, the free dictionary. ... The Mouse Genome Informatics (MGI) website is run by The Jackson Laboratory. ... HomoloGene[1], a tool of the National Center for Biotechnology Information (NCBI)[2], is a system for automated detection of homologs (similarity attributable to descent from a common ancestor) among the annotated genes of several completely sequenced eukaryotic genomes. ... The Gene Ontology project, or GO, provides a controlled vocabulary to describe gene and gene product attributes in any organism. ... More reference expression data
Orthologs
	Human	Mouse
Entrez	9370	11450
Ensembl	ENSG00000181092	ENSMUSG00000022878
Uniprot	Q15848	Q6GTX4
Refseq	NM_004797 (mRNA) NP_004788 (protein)	NM_009605 (mRNA) NP_033735 (protein)
Location	Chr 3: 188.04 - 188.06 Mb	Chr 16: 23.06 - 23.07 Mb
Pubmed search	[1]	[2]

Adiponectin (also referred to as Acrp30, apM1) is a protein hormone that modulates a number of metabolic processes, including glucose regulation and fatty acid catabolism. Adiponectin is exclusively secreted from adipose tissue into the bloodstream and is very abundant in plasma relative to many hormones. Levels of the hormone are inversely correlated with body fat percentage in adults, while the association in infants and young children is more unclear. The hormone plays a role in the suppression of the metabolic derangements that may result in type 2 diabetes, obesity, atherosclerosis and non-alcoholic fatty liver disease (NAFLD). The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Ensembl is a bioinformatics research project aiming to develop a software system which produces and maintains automatic annotation on selected eukaryotic genomes. It is run in a collaboration between the Wellcome Trust Sanger Institute and the European Bioinformatics Institute, an outstation of the European Molecular Biology Laboratory. ... UniProt is the universal protein database, a central repository of protein data created by combining Swiss-Prot, TrEMBL and PIR. This makes it the worlds most comprehensive resource on protein information. ... Medline is a comprehensive literature database of life sciences and biomedical information. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... Short and long arms Chromosome. ... Chromosome 1 is, by convention, the designation for the largest human chromosome. ... The Entrez logo The Entrez Global Query Cross-Database Search System allows access to databases at the National Center for Biotechnology Information (NCBI) website. ... Look up Hugo in Wiktionary, the free dictionary. ... The Mendelian Inheritance in Man project is a database that catalogues all the known diseases with a genetic component, and - when possible - links them to the relevant genes in the human genome. ... National Center for Biotechnology Information logo The National Center for Biotechnology Information (NCBI) is part of the United States National Library of Medicine (NLM), a branch of the National Institutes of Health. ... Swiss-Prot is a curated biological database of protein sequences created in 1986 by Amos Bairoch during his PhD and developed by the Swiss Institute of Bioinformatics and the European Bioinformatics Institute. ... Short and long arms Chromosome. ... Chromosome 12 is one of the 23 pairs of chromosomes in humans. ... For other uses, see Hormone (disambiguation). ... Glucose (Glc), a monosaccharide (or simple sugar), is an important carbohydrate in biology. ... Not to be confused with fats. ... Anabolism is the aspect of metabolism that contributes to growth. ... Adipose tissue is one of the main types of connective tissue. ... For other uses, see Blood (disambiguation). ... Blood plasma is the liquid component of blood, in which the blood cells are suspended. ... Diabetes mellitus type 2 or Type 2 Diabetes (formerly called non-insulin-dependent diabetes (NIDDM), obesity-related diabetes, or adult-onset diabetes) is a metabolic disorder that is primarily characterized by insulin resistance, relative insulin deficiency, and hyperglycemia. ... Non-alcoholic fatty liver disease (NAFLD) is fatty inflammation of the liver when this is not due to excessive alcohol use. ...

Research history

Adiponectin was first characterised in mice as a transcript overexpressed in preadipocytes (precursors of fat cells) differentiating into adipocytes. The human homologue was identified as the most abundant transcript in adipose tissue. Contrary to expectations, despite being produced in adipose tissue, adiponectin was found to be decreased in obesity. This downregulation has not been fully explained. The gene was localised to chromosome 3p27, a region highlighted as affecting genetic susceptibility to type 2 diabetes and obesity. Supplementation by differing forms of adiponectin were able to improve insulin control, blood glucose and triglyceride levels in mouse models. The interaction of mRNA in a eukaryote cell. ... Adipose tissue is an anatomical term for loose connective tissue composed of energy in the form of fat, although it also cushions and insulates the body. ... Adipose tissue is one of the main types of connective tissue. ... Not to be confused with inulin. ...

The gene was investigated for variants that predispose to type 2 diabetes. Several single nucleotide polymorphisms in the coding region and surrounding sequence were identified from several different populations, with varying prevalences, degrees of association and strength of effect on type 2 diabetes. DNA strand 1 differs from DNA strand 2 at a single base-pair location (a C/T polymorphism). ...

Structure and function

Adiponectin is a 244-amino-acid-long polypeptide. There are four distinct regions of adiponectin. The first is a short signal squence that targets the hormone for secretion outside the cell; next is a short region that varies between species; the third is a 65-amino acid region with similarity to collagenous proteins; the last is a globular domain. Overall this gene shows similarity to the complement 1Q factors. However, when the 3-dimensional structure of the globular region was determined, a striking similarity to TNFα was observed, despite unrelated protein sequences. In medicine, tumor necrosis factor alpha (TNFα, cachexin or cachectin) is an important cytokine involved in systemic inflammation and the acute phase response. ...

Adiponectin is secreted into the bloodsteam where it accounts for approximately 0.01% of all plasma protein at around 5-10 μg/mL. Plasma concentrations reveal a sexual dimorphism, with females having higher levels than males. Levels of adiponectin are reduced in diabetics compared to non-diabetics. Weight reduction significantly increases circulating levels. Female (left) and male Common Pheasant, illustrating the dramatic difference in both color and size, between the sexes Sexual dimorphism is the systematic difference in form between individuals of different sex in the same species. ...

Adiponectin automatically self-associates into larger structures. Initially, three adiponectin molecules bind together to form a homotrimer. The trimers continue to self-associate and form hexamers or dodecamers. Like the plasma concentration, the relative levels of the higher-order structures are sexually dimorphic, where females have increased proportions of the high-molecular weight forms. Questions remain about what the physiologically active forms of the protein are and how they carry out their action. Trimer might refer to: trimer (chemistry), a reaction product composed of three identical molecules trimer (biochemistry), a compound of three macromolecules non-covalently bound This is a disambiguation page: a list of articles associated with the same title. ...

Adiponectin binds to a number of receptors. So far, two receptors have been identified, with homology to G protein-coupled receptors. These have distinct tissue specificities within the body and have different affinities to the various forms of adiponectin. The receptors affect the downstream target AMP kinase, an important cellular metabolic rate control point. Expression of the receptors are correlated with insulin levels, as well as reduced in mouse models of diabetes, particularly in skeletal muscle and adipose tissue. In biochemistry, a receptor is a protein on the cell membrane or within the cytoplasm or cell nucleus that binds to a specific molecule (a ligand), such as a neurotransmitter, hormone, or other substance, and initiates the cellular response to the ligand. ... In biology, homology is any similarity between structures that is due to their shared ancestry. ... A Mu-opioid G protein-coupled receptor with its agonist Figure 1. ... 5AMP-activated protein kinase or AMPK consists of three proteins (subunits) that together make a functional enzyme, conserved from yeast to humans, that plays a role in cellular energy homeostasis. ... A top-down view of skeletal muscle Skeletal muscle is a type of striated muscle, usually attached to the skeleton. ...

Adiponectin exerts some of its weight reduction effects via the brain. This is similar to the action of leptin, but the two hormones perform complementary actions, and can have additive effects. For other uses, see Brain (disambiguation). ... RNA expression pattern Orthologs Human Mouse Entrez Ensembl Uniprot Refseq Location Pubmed search Leptin (from the Greek word leptos, meaning thin) is a 16 kDa protein hormone that plays a key role in regulating energy intake and energy expenditure, including the regulation (decrease) of appetite and (increase) of metabolism. ...

Metabolic effects

Adiponectin affects:

• glucose flux
  • gluconeogenesis
  • glucose uptake
• lipid catabolism
  • β-oxidation
  • triglyceride clearance
• protection from endothelial dysfunction (important facet of atherosclerotic formation)
• insulin sensitivity
• weight loss

Pyruvic acid Oxaloacetic acid Phosphoenolpyruvate Fructose 1,6-bisphosphate Fructose 6-phosphate Glucose-6-phosphate Glucose Gluconeogenesis is the generation of glucose from non-sugar carbon substrates like pyruvate, lactate, glycerol, and amino acids (primarily alanine and glutamine). ... Beta oxidation is the process by which fats, in the form of Acyl-CoA molecules, are broken down in the mitochondria to generate Acetyl-CoA, the entry molecule for the Krebs Cycle. ... The endothelium is the layer of thin, flat cells that lines the interior surface of blood vessels, forming an interface between circulating blood in the lumen and the rest of the vessel wall. ... Insulin sensitivity is the opposite of insulin resistance. ...

Pharmaceutical therapy

Because adiponectin is a novel hormone, no therapy has yet been developed with adiponectin and it may be some years before clinical trials commence. One obvious pharmaceutical treatment would be the administration of adiponectin; in mouse models such administration has shown positive effects. Problems to be overcome prior to human administration include establishing what the biologically active molecule is, what role post-translational modifications have upon the function and associated difficulties in generating biologically active molecules on a large scale. However, this remains a promising area of research for clinical therapy in diseases such as obesity, type 2 diabetes and fatty liver disease. This box:      In health care, a clinical trial is a comparison test of a medication or other medical treatment (such as a medical device), versus a placebo (inactive look-a-like), other medications or devices, or the standard medical treatment for a patients condition. ... Posttranslational modification means the chemical modification of a protein after its translation. ...

Further reading