8.A.94.  The Adiponectin (Adiponectin) Family 

Adiponectin is an important adipokine involved in the control of fat metabolism and insulin sensitivity, with direct anti-diabetic, anti-atherogenic and anti-inflammatory activities (Yamauchi et al. 2001). It stimulates AMPK phosphorylation and activation in the liver and skeletal muscle, enhancing glucose utilization and fatty-acid consumption. It antagonizes TNF-alpha by negatively regulating its expression in various tissues such as liver and macrophages, and also by counteracting its effects. It inhibits endothelial NF-kappa-B signaling through a cAMP-dependent pathway. It may also play a role in cell growth, angiogenesis and tissue remodeling by binding and sequestering various growth factors with distinct binding affinities, depending on the type of complex, LMW, MMW or HMW (Yamauchi et al. 2001)

Obesity is a major risk factor for liver fibrosis, associated with low levels of adiponectin. Adiponectin has antifibrogenic activity protecting from liver fibrosis, which is mainly driven by activated hepatic stellate cells (HSC). Aquaporins allow the movement of water and, in cases of aquaglyceroporins (AQPs), of glycerol that is needed in quiescent HSC for lipogenesis. Expression of various AQPs in liver is altered by obesity. Tardelli et al. 2017 identified obesity-associated factors that are related to HSC AQP expressional activation and lipid storage. Correlations between serum adipokine levels and hepatic AQP gene expression were analyzed from a cohort of obese patients. AQP and fibrotic gene expression was determined in a HSC line (LX2) and in a hepatocyte cell line (HepG2) after stimulation with adiponectin using quantitative real-time polymerase chain reaction. It was found that serum adiponectin correlated with liver AQP3, AQP7, AQP9 gene expression. In vitro, adiponectin induced upregulation of AQP3 gene and AQP3 protein expression in human HSCs, but not in hepatocytes, while AQP7, AQP9 remained undetectable. Accordingly, HSC stimulated with adiponectin increased glycerol uptake, lipogenic gene expression, and lipid storage while downregulating activation/fibrosis markers. Thus, adiponectin is a potent inhibitor of HSC activation and induces AQPs expression.




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TC#NameOrganismal TypeExample

Adiponectin of 244 aas and possibly one N-terminal TMS. Description and significance of the human protein can be found in the family description.  Regulates expression of aquaporins, particularly Aqp3, which transports water and glycerol (TC# 1.A.8.9.1 for the rat ortholog) (Tardelli et al. 2017).

Adiponectin of Homo sapiens


Secreted complement C1q and tumor necrosis factor-related protein 9 of 333 aas and possibly 1 or 2 TMSs. It is a probable adipokine that activates AMPK, AKT, and p44/42 MAPK signaling pathways (Xin et al. 2014). It may have a protective role in cirrhosis progression (Hicks et al. 2017).

C1q or CTRP9 of Homo sapiens


Complement C1q tumor necrosis factor-related protein 9, CTRP9, of 302 aas and 1 N-terminal TMS. AjCTRP9 is a novel adipokine with pleiotropic functions in immunity and metabolism (Shao et al. 2017).

CTRP9 of Apostichopus japonicus


Complement C1q tumor necrosis factor-related protein 3 isoform X5 of 357 aas and 1 N-terminal TMS.

C1q protein 3 isoform X5 of Papio anubis


Complement C1q tumor necrosis factor-related protein 1-like of 245 aas and 1 N-terminal TMS.

C1QTNF6A of Nothobranchius furzeri (Turquois hillifish)


C1QL2 of 287 aas and 1 N-terminal TMS as well as several C-terminal moderate peaks of hydrophobicity that might be TMSs. It may regulate the number of excitatory synapses that are formed on hippocampus neurons but has no effect on inhibitory synapses. May also be a subunit of AMPA receptors (Matthews et al. 2021).

C1QL2 of Homo sapiens