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Context We have recently shown that the secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is upregulated in human obesity and that overexpression of scEMC10 promotes, whereas antibody neutralization of circulating scEMC10 prevents diet-induced obesity in mice. Objective To explore associations of serum scEMC10 with body mass index (BMI), resting metabolism rate (RMR), and age in humans. Design A cross-sectional study. Setting and Patients A total of 833 participants from a Chinese physical examination cohort and 191 participants from the Leipzig Obesity Biobank cohort. Main Outcome Measures Serum scEMC10 concentrations are measured using chemiluminescent immunoassay. RMR is calculated based on measurements from indirect calorimetry with an open-circuit ventilated-hood system. Results In the Chinese physical examination cohort, a J-shaped nonlinear correlation between BMI and serum scEMC10 was identified in participants where underweight, overweight, and obese people all presented higher serum scEMC10 levels than normal weight people. Participants younger than age 30 years old exhibited significantly higher serum scEMC10 levels than those older than 50 years of age. In addition, participants aged 30 to 40 years also had significantly higher serum scEMC10 levels than those aged 50 to 60 years. In the Leipzig Obesity Biobank cohort, we observed a significantly negative correlation between serum scEMC10 and resting energy expenditure after adjusting for BMI. Participants in the highest quartile of serum scEMC10 levels had significantly lower RMR than those in the first quartile. RMR had an independently inverse association with serum scEMC10. Conclusions Serum scEMC10 levels are negatively associated with age and RMR in humans.

Aims To explore the relationship between serum growth differentiation factor 15 (GDF15) and metabolic abnormalities in Chinese pregnant women. Materials and Methods We recruited 200 patients with gestational diabetes mellitus (GDM) and 211 matched normal control within 24–28 weeks of pregnancy. Enzyme‐linked immunosorbent assay (ELISA) was used to determine the serum GDF15 levels of all participants. Then we grouped participants according to the number of metabolic abnormalities (including blood glucose, blood lipids and blood pressure), divided them into a normal metabolic group, one metabolic abnormality group, two or more metabolic abnormalities group. Finally, multinomial logistic regression analysis was used to estimate the odds radio (OR) and 95% CIs expressing the association between GDF15 and metabolic abnormalities in pregnant women. Results Through bivariate correlation analysis, we found that serum GDF15 is linearly correlated with glucose metabolism indices, such as 1h‐PG, 2h‐PG, HbA1c (all P 1), and the risk of multiple metabolic abnormalities was higher. As the number of metabolic abnormalities increased, serum GDF15 levels also were elevated (P, Our results found that the serum growth differentiation factor 15 plays an important role in metabolic abnormalities in the pregnant population and it may provide new ideas for the prevention and diagnosis of metabolic abnormalities during pregnancy. We believe this work is scientifically valid.

Spexin plays a role in regulating glucose metabolism. This study investigated the spexin levels in different glycemic status and its association with insulin secretion in humans.A total of 462 subjects were recruited in this study, including 52 healthy subjects, 106 first-degree relatives (FDRs) of type 2 diabetes mellitus (T2DM), 115 impaired glucose regulation (IGR), 80 newly diagnosed T2DM, and 106 established T2DM. Serum spexin was measured using ELISA. The homeostasis model assessment of insulin resistance (HOMA2-IR) and β-cell function (HOMA2-β), and Stumvoll index estimating first- and second-phase insulin secretion were calculated.Spexin levels were higher in FDRs [235.53 pg/ml (185.28, 293.95)] and IGR [239.79 pg/ml (191.52, 301.69)], comparable in newly diagnosed T2DM [224.68 pg/ml (187.37, 279.74)], and lower in established T2DM [100.11 pg/ml (78.50, 137.34)], compared with healthy subjects [200.23 pg/ml (160.32, 275.65)]. Spexin levels were negatively correlated with fasting plasma glucose (FPG) (r = - 0.355, P 0.001), hemoglobin A1C (HbA1c) (r = - 0.379, P 0.001), and HOMA2-IR (r = - 0.225, P 0.001), and positively correlated with HOMA2-β (r = 0.245, P 0.001) after adjusting for age, sex, and BMI. Multivariate linear regression analysis showed that established T2DM and HOMA2-β were independently associated with serum spexin levels.Serum spexin levels represented as a bell-shaped curve along the glycemic continuum and is closely related with insulin secretion in humans.

Seedling emergence in monocots depends mainly on mesocotyl elongation, requiring coordination between developmental signals and environmental stimuli. Strigolactones (SLs) and karrikins are butenolide compounds that regulate various developmental processes; both are able to negatively regulate rice (Oryza sativa) mesocotyl elongation in the dark. Here, we report that a karrikin signaling complex, DWARF14-LIKE (D14L)-DWARF3 (D3)-O. sativa SUPPRESSOR OF MAX2 1 (OsSMAX1) mediates the regulation of rice mesocotyl elongation in the dark. We demonstrate that D14L recognizes the karrikin signal and recruits the SCF(D3) ubiquitin ligase for the ubiquitination and degradation of OsSMAX1, mirroring the SL-induced and D14- and D3-dependent ubiquitination and degradation of D53. Overexpression of OsSMAX1 promoted mesocotyl elongation in the dark, whereas knockout of OsSMAX1 suppressed the elongated-mesocotyl phenotypes of d14l and d3. OsSMAX1 localizes to the nucleus and interacts with TOPLESS-RELATED PROTEINs, regulating downstream gene expression. Moreover, we showed that the GR24 enantiomers GR24(5DS) and GR24(ent-5DS) specifically inhibit mesocotyl elongation and regulate downstream gene expression in a D14- and D14L-dependent manner, respectively. Our work revealed that karrikin and SL signaling play parallel and additive roles in modulating downstream gene expression and negatively regulating mesocotyl elongation in the dark.

Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterised secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in humans with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a novel circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.

Secreted isoform of endoplasmic reticulum membrane complex subunit 10 (scEMC10) is a poorly characterized secreted protein of largely unknown physiological function. Here we demonstrate that scEMC10 is upregulated in people with obesity and is positively associated with insulin resistance. Consistent with a causal role for scEMC10 in obesity, Emc10-/- mice are resistant to diet-induced obesity due to an increase in energy expenditure, while scEMC10 overexpression decreases energy expenditure, thus promoting obesity in mouse. Furthermore, neutralization of circulating scEMC10 using a monoclonal antibody reduces body weight and enhances insulin sensitivity in obese mice. Mechanistically, we provide evidence that scEMC10 can be transported into cells where it binds to the catalytic subunit of PKA and inhibits its stimulatory action on CREB while ablation of EMC10 promotes thermogenesis in adipocytes via activation of the PKA signalling pathway and its downstream targets. Taken together, our data identify scEMC10 as a circulating inhibitor of thermogenesis and a potential therapeutic target for obesity and its cardiometabolic complications.

Aims/Introduction High plasma 3‐carboxy‐4‐methyl‐5‐propyl‐2‐furanpropanoic acid (CMPF) levels are significantly associated with type 2 diabetes mellitus, which is usually accompanied by metabolic syndrome and non‐alcoholic fatty liver disease (NAFLD) with increased triglyceride levels. Thus, we hypothesized that elevated CMPF levels might be related to lipid metabolism and NAFLD risk. Materials and Methods Serum CMPF levels were determined using an enzyme‐linked immunosorbent assay in a total of 466 individuals, including 116 controls with no NAFLD or type 2 diabetes mellitus, 53 individuals with NAFLD but no type 2 diabetes mellitus, 151 individuals with type 2 diabetes mellitus but no NAFLD, and 146 individuals with both NAFLD and type 2 diabetes mellitus. The associations with age, blood pressure, lipid profiles, body mass index and liver injury marker levels were examined, and a meta‐analysis of non‐diabetic and diabetic groups was carried out to detect the combined effects. Results The CMPF concentration in NAFLD patients was significantly lower than individuals without NAFLD in both the non‐diabetic group (P