Acrp30, familiarly known as adiponectin, is a member of the adipocytokine family – cytokines expressed specifically in the adipose tissue. Our antibody catalogue contains 24 adiponectin antibodies, proteins and lysates, which have come under the spotlight recently with respect to mitochondrial biogenesis.
Acrp30 is known to positively regulate lipid and glucose metabolism. Adiponectin deficiency is connected to obesity resulting from dyslipidemia, insulin resistance and mitochondrial dysfunction. In 2003, Yamauchi et al identified two binding receptors, Adiponectin Receptor 1and 2 (Adipo R1/R2, also known as Adipor1/2). Further research revealed Adipo R1 is predominantly expressed in skeletal muscle, the body’s main site for the utilising of glucose.
Recently, M. Iwabu et al published a paper confirming Adipor1 was integral to glucose tolerance and insulin sensitivity, using an Adipo R1-deficient mouse model (the muscle-Adipo R1KO strain). Exceptionally high levels of plasma glucose and insulin were revealed in vivo, while antibody assays revealed significant alterations in signalling molecules phosphorylated by insulin stimulation, among them p70 S6 kinase, IRS-1, Akt and JNK. Decreased activity of mitochondria-specific proteins, including the transcription factor PGC1, a regulator of mitochondrial biogenesis, were also noted. Other effects included enhanced oxidative stress in the muscle tissue, and impaired fatty acid oxidation. Despite the absence of Adipor1, some of these effects were partially overcome when muscle-Adipo R1KO mice were subjected to exercise, indicating exercise as a possible therapeutic tool in humans deficient in adiponectin.
A number of in vitro knockdown studies, involving a number of antibodies, siRNAs and specific inhibitors, were then performed on normal mouse myocyes. It was seen that Adiponectin-induced mitochondrial biogenesis was reduced when Adipo R1, CAMKK beta, PGC1 alpha and AMPK alpha1/alpha 2 were inhibited. Also, PGC1 alpha expression was blocked when CAMKK beta and Adipo R1 were inhibited by siRNAs.
The studies showed Adiponectin mediated extracellular calcium influx in normal cells. In the absence of Adipo R1 this mechanism was defective. It was suggested that Adiponectin-induced calcium influx is essential for activation of a signalling cascade, involving CaMKK beta, PGC1 alpha, AMPK and SIRT1, which ultimately promotes transcription of mitochondrial biogenesis proteins via the transcription factor PGC1.
Studies continue into Adipor1 signalling and the calcium influx. We at Novus Biologicals have an extensive antibody catalog covering this area of research.
