However, contrary to the above studies, MEG3 knockdown by intravenous delivery of locked nucleic acid-modified antisense oligonucleotides against MEG3, which led to 94.8%, 89.8% and 68.9% reduction of MEG3 expression in the liver, skeletal muscle and epididymal white adipose tissue (eWAT), respectively, did not improve insulin sensitivity but exacerbated overall glucose intolerance and IR in mice fed on HFD for 10 weeks. This evidence concerns the gene INS and Glucose intolerance.