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Genetic predispositions and environmental exposures are regarded as the main predictors of respiratory disease development. Although the impact of dietary essential nutrient deficiencies on cardiovascular disease, obesity, and type II diabetes has been widely studied, it remains poorly explored in chronic respiratory diseases. Dietary choline and methionine deficiencies are common in the population, and their impact on pulmonary homeostasis is currently unknown. Mice were fed choline- and/or methionine-deficient diets while being exposed to room-air or cigarette smoke for up to 4 wk. Lung functions were assessed using the FlexiVent. Pulmonary transcriptional activity was assessed using gene expression microarrays and quantitative PCR. Immune cells, cytokines, and phosphatidylcholine were quantified in the bronchoalveolar lavage. In this study, we found that short-term dietary choline and/or methionine deficiencies significantly affect lung function in mice in a reversible manner. It also reduced transcriptional levels of collagens and elastin as well as pulmonary surfactant phosphatidylcholine levels. We also found that dietary choline and/or methionine deficiencies markedly interfered with the pulmonary response to cigarette smoke exposure, modulating lung function and dampening inflammation. These findings clearly show that dietary choline and/or methionine deficiencies can have dramatic pathophysiological effects on the lungs and can also affect the pathobiology of cigarette smoke-induced pulmonary alterations. Expanding our knowledge in the field of “nutri-respiratory research” may reveal a crucial role for essential nutrients in pulmonary health and disease, which may prove to be as relevant as genetic predispositions and environmental exposures.

To identify candidate causal genes of asthma, we performed a genome-wide association study (GWAS) in UK Biobank on a broad asthma definition (n = 56,167 asthma cases and 352,255 controls). We then carried out functional mapping through transcriptome-wide association studies (TWAS) and Mendelian randomization in lung (n = 1,038) and blood (n = 31,684) tissues. The GWAS reveals 72 asthma-associated loci from 116 independent significant variants (PGWAS, Kim Valette et al. perform a genomic study on asthma integrating genome-wide association study, functional mapping using lung and blood transcriptome-wide profiles, as well as Mendelian randomization. They show candidate causal genes expressed in lung and blood tissues that are putative therapeutic targets for asthma.

Objectives Hepatokines are proteins secreted by the liver that impact the functions of the liver and various tissues through autocrine, paracrine, and endocrine signaling. Recently, Tsukushi (TSK) was identified as a new hepatokine that is induced by obesity and cold exposure. It was proposed that TSK controls sympathetic innervation and thermogenesis in brown adipose tissue (BAT) and that loss of TSK protects against diet-induced obesity and improves glucose homeostasis. Here we report the impact of deleting and/or overexpressing TSK on BAT thermogenic capacity, body weight regulation, and glucose homeostasis. Methods We measured the expression of thermogenic genes and markers of BAT innervation and activation in TSK-null and TSK-overexpressing mice. Body weight, body temperature, and parameters of glucose homeostasis were also assessed in the context of TSK loss and overexpression. Results The loss of TSK did not affect the thermogenic activation of BAT. We found that TSK-null mice were not protected against the development of obesity and did not show improvement in glucose tolerance. The overexpression of TSK also failed to modulate thermogenesis, body weight gain, and glucose homeostasis in mice. Conclusions TSK is not a significant regulator of BAT thermogenesis and is unlikely to represent an effective target to prevent obesity and improve glucose homeostasis., Highlights • Loss of TSK does not affect brown fat thermogenic capacity. • Loss of TSK does not protect mice against the development of obesity. • Loss of TSK does not improve glucose homeostasis. • Overexpression of TSK does not affect thermogenesis, body weight gain and glucose homeostasis.

Nonalcoholic fatty liver disease (NAFLD) prevails in obesity and is linked to several health complications including dyslipidemia and atherosclerosis. How exactly NAFLD induces atherogenic dyslipidemia to promote cardiovascular diseases is still elusive. Here, we identify Tsukushi (TSK) as a hepatokine induced in response to NAFLD. We show that both endoplasmic reticulum stress and inflammation promote the expression and release of TSK in mice. In humans, hepatic TSK expression is also associated with steatosis, and its circulating levels are markedly increased in patients suffering from acetaminophen-induced acute liver failure (ALF), a condition linked to severe hepatic inflammation. In these patients, elevated blood TSK levels were associated with decreased transplant-free survival at hospital discharge, suggesting that TSK could have a prognostic significance. Gain- and loss-of-function studies in mice revealed that TSK impacts systemic cholesterol homeostasis. TSK reduces circulating HDL cholesterol, lowers cholesterol efflux capacity, and decreases cholesterol-to-bile acid conversion in the liver. Our data identify the hepatokine TSK as a blood biomarker of liver stress that could link NAFLD to the development of atherogenic dyslipidemia and atherosclerosis.

E‐cigarette use has exploded in the past years, especially among young adults and smokers desiring to quit. While concerns are mostly based on the presence of nicotine and flavors, pulmonary effects of propylene glycol and glycerol inhalation, the main solvents of e‐liquid have not been thoroughly investigated. In this preclinical study, mice were exposed 2 h daily for up to 8 weeks to vapors of propylene glycol and/or glycerol generated by an e‐cigarette. Lung transcriptome analysis revealed it affected the expression level of genes of the circadian molecular clock, despite causing no inflammatory response. Periodical sacrifices showed that the rhythmicity of these regulatory genes was indeed altered in the lungs, but also in the liver, kidney, skeletal muscle, and brain. E‐cigarette exposure also altered the expression of rhythmic genes (i.e., hspa1a and hspa1b), suggesting that alterations to the ‘clock genes’ could translate into systemic biological alterations. This study reveals that the major solvents used in e‐cigarettes propylene glycol and glycerol, not nicotine or flavors, have unsuspected effects on gene expression of the molecular clock that are to be taken seriously, especially considering the fundamental role of the circadian rhythm in health and disease.