Figure 5 Mechanisms of adiponectin actions in the kidney

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Figure 5 Mechanisms of adiponectin actions in the kidney Figure 5 | Mechanisms of adiponectin actions in the kidney. Adipocytes are the major source of circulating adiponectin, although the kidneys might also produce it. Adiponectin acts upon its receptors, ADIPOR1 and ADIPOR2, to activate 5′-AMP-activated protein kinase catalytic subunit α-1 (PRKAA1; also known as AMPK) and peroxisome proliferator-activated receptor-α (PPARα) signalling, respectively. Adiponectin receptors also possess ceramidase activity, which enables ceramides to be converted to sphingosines and fatty acids. Combined, these actions of adiponectin coordinately regulate energy metabolism, cellular oxidative stress and inflammation. Dysregulation of these cellular events can lead to various renal abnormalities, including fibrosis, glomerulosclerosis and albuminuria. Some compounds such as 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR), resveratrol (RSV) and berberine (BBR) elevate circulating adiponectin levels and thus improve kidney dysfunction by enhancing adiponectin signalling. In addition, direct activation of AMPK by compounds such as PF-06409577 and PF-249 also ameliorate kidney disease. CaMKK 2, calcium/calmodulin-dependent protein kinase kinase 2; LBK1 (also known as STK11), serine/threonine-protein kinase STK11. Zhu, Q. & Scherer, P. E. (2017) Immunologic and endocrine functions of adipose tissue: implications for kidney disease Nat. Rev. Nephrol. doi:10.1038/nrneph.2017.157