Potential role of GPCRs as signal transducers in early programming of metabolic syndrome

Potential mechanisms of early programming of metabolic syndrome (MetS). This figure represents some of the proposed mechanisms by which GPCR may participate in the early programming of metabolic syndrome (MetS). Background colors represent different stages in growth and development when the programming-inducing insults occur (prenatal and early childhood stages), when the preclinical manifestations of MetS are manifested (childhood and early adulthood) and when the components of MetS can be detected (adult and aged population). Letter A represent GPCRs involved in appetite regulation (such as receptors for ghrelin, the hypocretins/orexins (hypocretin 1/orexin A, hypocretin 2/orexin B), melanin-concentrating hormone (MCH), neuropeptide B (NPB)/neuropeptide W (NPW), Galanin and GPR162, oxerins (which bind to the two GPCRs, OX1 and OX2), neuropeptide Y and endocannabinoid receptors CB1 and CB2. Letter B represents certain free fatty acids (FFA)-activated GPCRs (such as GPR120) as well as phospholipid-activated GPCRs (such as LPA1-5, GPR87 and P2Y5) that have been involved in adipocyte differentiation, maturation and paracrine release of growth factors. Letter C represents GPCRs affecting traditional insulin secretion and signaling in different organs such as β-arrestin-2 signal complex, GPR54, GPR40, GPR43, GPR84, and GPR119. Letter D represents the receptors for prostacyclin, angiotensin II receptors, sphingosine 1-phosphate, endothelin-1, thrombin and thromboxane A2, all of which are ligands of GPCRs and are involved in vascular function, proliferation and remodeling.