The mTORC1 complex in pre-osteoblasts regulates whole-body energy metabolism independently of osteocalcin

Overnutrition causes hyperactivation of mTORC1-dependent negative feedback loops leading to the downregulation of insulin signaling and development of insulin resistance.In osteoblasts(OBs),insulin signaling plays a crucial role in the control of systemic glucose homeostasis.We utilized mice with conditional deletion of Rptor to investigate how the loss of mTORC1 function in OB affects glucose metabolism under normal and overnutrition dietary states.Compared to the controls,chow-fed Rptorob−/−mice had substantially less fat mass and exhibited adipocyte hyperplasia.Remarkably,upon feeding with high-fat diet,mice with pre-and post-natal deletion of Rptor in OBs were protected from diet-induced obesity and exhibited improved glucose metabolism with lower fasting glucose and insulin levels,increased glucose tolerance and insulin sensitivity.This leanness and resistance to weight gain was not attributable to changes in food intake,physical activity or lipid absorption but instead was due to increased energy expenditure and greater whole-body substrate flexibility.RNA-seq revealed an increase in glycolysis and skeletal insulin signaling pathways,which correlated with the potentiation of insulin signaling and increased insulin-dependent glucose uptake in Rptorknockout osteoblasts.Collectively,these findings point to a critical role for the mTORC1 complex in the skeletal regulation of wholebody glucose metabolism and the skeletal development of insulin resistance.

Tissue and regional expression patterns of dicistronic tRNA–mRNA transcripts in grapevine (Vitis vinifera) and their evolutionary co-appearance with vasculature in land plants

Transfer RNAs(tRNA)are crucial adaptor molecules between messenger RNA(mRNA)and amino acids.Recent evidence in plants suggests that dicistronic tRNA-like structures also act as mobile signals for mRNA transcripts to move between distant tissues.Co-transcription is not a common feature in the plant nuclear genome and,in the few cases where polycistronic transcripts have been found,they include non-coding RNA species,such as small nucleolar RNAs and microRNAs.It is not known,however,the extent to which dicistronic transcripts of tRNA and mRNAs are expressed in field-grown plants,or the factors contributing to their expression.We analysed tRNA–mRNA dicistronic transcripts in the major horticultural crop grapevine(Vitis vinifera)using a novel pipeline developed to identify dicistronic transcripts from high-throughput RNA-sequencing data.We identified dicistronic tRNA–mRNA in leaf and berry samples from 22 commercial vineyards.Of the 124 tRNA genes that were expressed in both tissues,18 tRNA were expressed forming part of 19 dicistronic tRNA–mRNAs.The presence and abundance of dicistronic molecules was tissue and geographic sub-region specific.In leaves,the expression patterns of dicistronic tRNA–mRNAs significantly correlated with tRNA expression,suggesting that their transcriptional regulation might be linked.We also found evidence of syntenic genomic arrangements of tRNAs and protein-coding genes between grapevine and Arabidopsis thaliana,and widespread prevalence of dicistronic tRNA–mRNA transcripts among vascular land plants but no evidence of these transcripts in non-vascular lineages.This suggests that the appearance of plant vasculature and tRNA–mRNA occurred concurrently during the evolution of land plants.