Figure 2.

Adiponectin receptor signaling regulates lipid metabolism through PPAR nuclear hormone receptors. The adiponectin receptor AdipoR2 senses membrane rigidification and converts ceramide (Cer) to sphingosine (Sph) via its intrinsic ceramidase activity. Sphingosine is phosphorylated by sphingosine kinases (Sphks) to generate sphingosine 1-phosphate (S1P), which acts as a signaling molecule and induces PPARγ. PPARγ transcriptionally activates stearoyl-CoA desaturases (SCDs) to increase fatty acid desaturation and membrane fluidity. In addition, AdipoR2 can promote PPARα function to enhance fatty acid (FA) catabolism. Upon treatment with saturated fatty acids, AdipoR2 affects the expression of enzymes involved in acyl chain remodeling, UFA synthesis and cholesterol biosynthesis. However, it is not known yet whether these processes are regulated indirectly or by signaling pathways and transcriptional regulators downstream of AdipoR2. P, phosphate; PPARα, peroxisome proliferator-activated receptor-α; PPARγ, peroxisome proliferator-activated receptor-γ; SREBP1, sterol regulatory element-binding protein-1; TF, transcription factor; UFA, unsaturated fatty acid.