Since increased circulating lipids and ensuing cardiomyocyte lipotoxicity and insulin resistance contribute to obesity-related cardiac complications [36], we examined whether incubation of HL-1 cardiomyocytes with 1.2 mM palmitate for 16 h, which led to impaired insulin-stimulated Akt phosphorylation at Ser473 (S1 Fig), can recapitulate changes in LPA receptor expression detected in ventricles and cardiomyocytes from obese-insulin resistant mice (Fig 2A and 2B). Here, INS is linked to obesity due to melanocortin 4 receptor deficiency.