Diabetes and pulmonary infection:how hyperglycaemia shapes the immune system

In a recent study published in Nature,Nobs and colleagues aimed to identify novel mechanisms that may explain why diabetes is associated with an increased susceptibility to viral respiratory infections.Their analyses revealed a central role of lung dendritic cells(DC)which exhibited several functional defects induced by hyperglycaemia and consequently result in impaired antiviral immune responses.

Cellular precision modulation of JAK1:tailoring therapies for allergic lung inflammation

In a recent publication published in Cell,Tamari et al.unraveled a previously unrecognized role of JAK1 signaling in vagal sensory neurons regulating the immune response to allergic lung inflammation.1 The authors show that sensory neuromodulation could be an important therapeutic avenue for the treatment of lung inflammation.It is now well established that the number of patients suffering from allergic disorders,like those suffering from obesity and the metabolic syndrome,is rapidly increasing world-wide,accelerating the burden on individual health and healthcare systems.Thus,basic and clinical researchers urgently need to develop novel therapeutics and approaches to limit or prevent disease development or progression.

Type 2 diabetes across populations of different ancestry: deconstructing the genomic landscape

In a recent study published in Nature Medicine,Smith and colleagues used data from 1.4 million individuals across 37 genome-wide association studies(GWAS)reflecting different genetic ancestral populations to identify 12 genetic clusters,mostly shared among the different populations,and associated the weighted sums of genetic variants of each cluster—termed as partitioned polygenic scores(pPSs)—with various lab-based,anthropometric and cardiometabolic traits.Their analyses extended previous studies on biological mechanisms linking genetics to type 2 diabetes(T2D)risk and pointed to both similarities of genetic clusters across multiple populations and differences regarding their contributions to overall T2D risk among different ethnicities.

Dysfunction of the adhesion G protein-coupled receptor latrophilin 1(ADGRL1/LPHN1)increases the risk of obesity

Obesity is one of the diseases with severe health consequences and rapidly increasing worldwide prevalence.Understanding the complex network of food intake and energy balance regulation is an essential prerequisite for pharmacological intervention with obesity.G protein-coupled receptors(GPCRs)are among the main modulators of metabolism and energy balance.They,for instance,regulate appetite and satiety in certain hypothalamic neurons,as well as glucose and lipid metabolism and hormone secretion from adipocytes.Mutations in some GPCRs,such as the melanocortin receptor type 4(MC4R),have been associated with early-onset obesity.Here,we identified the adhesion GPCR latrophilin 1(ADGRL1/LPHN1)as a member of the regulating network governing food intake and the maintenance of energy balance.Deficiency of the highly conserved receptor in mice results in increased food consumption and severe obesity,accompanied by dysregulation of glucose homeostasis.Consistently,we identified a partially inactivating mutation in human ADGRL1/LPHN1 in a patient suffering from obesity.Therefore,we propose that LPHN1 dysfunction is a risk factor for obesity development.

Highlights of the 2nd International Symposium on Tribbles and Diseases: tribbles tremble in therapeutics for immunity, metabolism, fundamental cell biology and cancer

The Tribbles(TRIB) family of pseudokinase proteins has been shown to play key roles in cell cycle, metabolic diseases, chronic inflammatory disease, and cancer development. A better understanding of the mechanisms of TRIB pseudokinases could provide new insights for disease development and help promote TRIB proteins as novel therapeutic targets for drug discovery. At the 2 nd International Symposium on Tribbles and Diseases held on May 7–9, 2018 in Beijing, China, a group of leading Tribbles scientists reported their findings and ongoing studies about the effects of the different TRIB proteins in the areas of immunity, metabolism, fundamental cell biology and cancer. Here, we summarize important and insightful overviews from 4 keynote lectures, 13 plenary lectures and 8 short talks that took place during this meeting. These findings may offer new insights for the understanding of the roles of TRIB pseudokinases in the development of various diseases.

The sugar-free paradox:cardiometabolic consequences of erythritol

In a recent study published in Nature Medicine,Witkowski and colleagues applied untargeted metabolomics studies in 1157 people at high risk for cardiovascular disease,comprising 22%with diabetes mellitus,followed by quantitative targeted analyses to identify circulating metabolites associated with an increased cardiovascular risk.