S1PR1 and Insulin resistance: Our observations that either S1P1 activation or S1P2 blockage ameliorated adipocyte hypertrophy, glucose intolerance, and inflammation in the VAT of obese mice [1,2] were consistent with previous results showing that apoM-carrying S1P worked through S1P1/3 to improve insulin resistance, whereas albumin-carrying S1P activated S1P2 to exacerbate it in obese adipocytes (Figure 2) [110,132] and the liver [106].