Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation

Open Access via the Elsevier Agreement L.K.H. designed the experiments with input from F.M., G.S.H.Y., and J.J.R.; F.M. and J.I. created the CRISPR-Cas9-deleted Gpr75 mouse line with input from A.M.; A.L.-P., C.M., B.Y.H.L., G.K.C.D., N.S., P.B.M.d.M., R.C., K.K., E.J.G., J.R.B.P., F.G., J.R.S., and J.J.R. performed experiments and/or data analysis; D.T. provided reagents and intellectual contributions; and L.K.H. and A.L.-P. wrote the manuscript with input from all other authors.Peer reviewe

Tide model accuracy in the Amundsen Sea, Antarctica, from radar interferometry observations of ice shelf motion

This study assesses the accuracy of tide model predictions in the Amundsen Sea sector of West Antarctica. Tide model accuracy in this region is poorly constrained, yet tide models contribute to simulations of ocean heat transfer and to the removal of tidal signals from satellite observations of ice shelves. We use two satellite-based interferometric synthetic aperture radar (InSAR) methods to measure the tidal motion of the Dotson Ice Shelf at multiple epochs: a single-difference technique that measures tidal displacement and a double-difference technique that measures changes in tidal displacement. We use these observations to evaluate predictions from three tide models (TPXO7.1, CATS2008a-opt, and FES2004). All three models perform comparably well, exhibiting root-mean-square deviations from the observations of ∼9 cm (single-difference technique) and ∼10 cm (double-difference technique). Care should be taken in generalizing these error statistics because (1) the Dotson Ice Shelf experiences relatively small semidiurnal tides and (2) our observations are not sensitive to all tidal constituents. An error analysis of our InSAR-based methods indicates measurement errors of 7 and 4 cm for the single-and double-difference techniques, respectively. A model-based correction for the effect of fluctuations in atmospheric pressure yields an ∼6% improvement in the agreement between tide model predictions and observations. This study suggests that tide model accuracy in the Amundsen Sea is comparable to other Antarctic regions where tide models are better constrained. These methods can be used to evaluate tide models in other remote Antarctic waters

Loss of GPR75 protects against non-alcoholic fatty liver disease and body fat accumulation

Approximately 1 in 4 people worldwide have non-alcoholic fatty liver disease (NAFLD); however, there are currently no medications to treat this condition. This study investigated the role of adiposity-associated orphan G protein-coupled receptor 75 (GPR75) in liver lipid accumulation. We profiled Gpr75 expression and report that it is most abundant in the brain. Next, we generated the first single-cell-level analysis of Gpr75 and identified a subpopulation co-expressed with key appetite-regulating hypothalamic neurons. CRISPR-Cas9-deleted Gpr75 mice fed a palatable western diet high in fat adjusted caloric intake to remain in energy balance, thereby preventing NAFLD. Consistent with mouse results, analysis of whole-exome sequencing data from 428,719 individuals (UK Biobank) revealed that variants in GPR75 are associated with a reduced likelihood of hepatic steatosis. Here, we provide a significant advance in understanding of the expression and function of GPR75, demonstrating that it is a promising pharmaceutical target for NAFLD treatment