Our results provide mechanistic insights of MGL's role in diet-induced obesity, lipid metabolic disorder, and regulation of appetite.-Yoshida, K., Kita, Y., Tokuoka, S. M., Hamano, F., Yamazaki, M., Sakimura, K., Kano, M., Shimizu, T. Monoacylglycerol lipase deficiency affects diet-induced obesity, fat absorption, and feeding behavior in CB<sub>1</sub> cannabinoid receptor-deficient mice.
Genome-wide association studies (GWAS) have detected association between variants in or near the <i>Lysophospholipase-like 1</i> (<i>LYPLAL1</i>) locus and metabolic traits, including central obesity, fatty liver and waist-to-hip ratio.
Pre-existing maternal obesity and GDM are associated with decreased expression in genes involved in fatty acid uptake and intracellular transport (LPL, FATP2, FATP6, FABPpm and ASCL1), triacylglyceride (TAG) biosynthesis (MGAT1,7 MGAT2 and DGAT1), lipogenesis (FASN) and lipolysis (PNPLA2, HSL and MGLL).
In contrast, the HFD produced pronounced reductions in skeletal muscle CB1-R and MAGL mRNA expression, whereas obesity did not affect muscular gene expression.
Moreover, in an obesity data study, we identified using the qMSAT two functional regions (MGLL promoter and MGLL 3'-untranslated region) where rare variants are associated with extreme obesity.