ABSTRACT
AIMS: Clusterin (encoded by CLU) is a novel adipokine. Serum clusterin levels were elevated in populations with obesity and diabetes. Adipose tissue insulin resistance (Adipo-IR) is proposed as an early metabolic defect that precedes systemic insulin resistance. Herein, we aimed to investigate the relationship between serum clusterin levels and Adipo-IR. CLU expression in human abdominal adipose tissues and clusterin secretion in human adipocytes was also explored. MATERIALS AND METHODS: A total of 201 participants (aged 18-62 years, 139 of whom were obese) were recruited. Enzyme-linked immunosorbent assay was used to measure serum clusterin levels. Adipo-IR was calculated from the product of fasting free fatty acids and fasting insulin levels. Transcriptome sequencing of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was performed. Human adipocytes were used to detect the secretion of clusterin. RESULTS: Serum clusterin levels were independently associated with Adipo-IR after adjusting for several confounding factors (standardised ß = 0.165, p = 0.021). CLU expression in VAT and SAT was associated with obesity-related metabolic risk factors. Higher CLU expression in VAT was accompanied by an increase in collagen accumulation. Clusterin secretion in differentiated human adipocytes was stimulated by insulin and inhibited by rosiglitazone. CONCLUSIONS: Clusterin is strongly associated with Adipo-IR. Serum clusterin may function as an effective indicator of adipose tissue insulin resistance.
ABSTRACT
The lack of inhibitory control toward foods may cause unhealthy eating behavior and lead to obesity. However, previous research failed to reach consensus on the alterations in event-related potential (ERP) markers of inhibitory control, i.e., N2 and P3. We hypothesized that the ERP effects of inhibitory control reported in previous food-based Go/NoGo studies might be obscured by non-inhibitory processes associated with stimulus probability. We designed two food-based Go/NoGo tasks composed of stimuli with the same type and frequency of occurrence (60% non-foods, 20% high-calorie foods, 20% low-calorie foods), one with response inhibition toward high- and the other toward low-calorie foods. Such an experimental design allowed us to isolate neural activity associated with inhibitory control from that associated with non-inhibitory processes by constructing ERP difference waves between NoGo and Go trials with the same frequency of occurrence. Electroencephalography data were collected from 32 obese participants and 29 normal-weight controls. Obese participants showed significantly lower accuracy in NoGo trials than normal-weight controls in both tasks. ERP data suggested inhibition-related effects for P3 (P3d) but not N2 in the difference waves, and obese participants showed significantly decreased P3d amplitudes than normal-weight controls in both tasks. In addition, we found that across both groups, individuals with larger waist-to-hip ratios showed smaller P3d amplitudes in both tasks, while such correlations between body mass index and P3d amplitude were only observed in the high-calorie task. Our findings suggest that the decreased effect of P3, not N2, might reflect the neural substrate of inhibitory control deficits in obese people. Thus, P3 could serve as an important neural marker in the future development of new therapeutic strategy that aims to improve inhibitory control in obesity.
Subject(s)
Electroencephalography , Evoked Potentials , Evoked Potentials/physiology , Feeding Behavior/physiology , Humans , Inhibition, Psychological , Obesity , Reaction Time/physiologyABSTRACT
OBJECTIVES: The need for a unified definition of weight loss (WL) after bariatric surgery has recently been highlighted. We aimed to evaluate the reliability of two clinically common WL indications including percentage of total WL (%TWL) and percentage of excess WL (%EWL) through comparing their performances in predicting metabolic syndrome (MetS) remission 1 year after bariatric surgery. METHODS: A total of 430 individuals with obesity who underwent bariatric surgery were enrolled. Participants were evaluated for changes in anthropometric parameters, metabolic indexes, MetS components and medications before and 1 year after surgery. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III criteria for Asian-Americans. RESULTS: The prevalence of MetS is 92.3% (397) at baseline. One year after bariatric surgery, 337 individuals (84.9%) were in MetS remission. The multivariate adjusted ORs were 1.16 (95% confidence interval [CI] 1.10-1.22) for each 1% increase in %TWL for MetS remission and 1.18 (95% CI 1.11-1.25) for each 5% increase in %EWL. This association with MetS remission remained statistically significant for %TWL after additional adjustment for %EWL (P for trend 0.029), and disappeared for %EWL. Receiver operating curve (ROC) analyses showed that the %TWL was more predictive than the %EWL (AUC%TWL vs. AUC%EWL, 0.749 vs. 0.700, p = 0.023). The Youden index indicated that the optimal %TWL cutoff point to identify MetS remission was 25%. CONCLUSIONS: We recommend that good responders to bariatric surgery should be defined as those exhibiting %TWL ≥ 25%.
Subject(s)
Bariatric Surgery/statistics & numerical data , Obesity, Morbid , Weight Loss/physiology , Adult , Female , Humans , Male , Metabolic Syndrome/complications , Middle Aged , Obesity, Morbid/complications , Obesity, Morbid/epidemiology , Obesity, Morbid/surgery , Retrospective Studies , Treatment OutcomeABSTRACT
An increase in the area treated with the fungicide thifluzamide has triggered concerns for soil ecosystem service providers such as earthworms. Here, we assessed effects of thifluzamide on earthworm (Eisenia fetida) biomarker indicators of stress responses and reproduction following exposure to 0, 0.1, 1.0, and 10.0â¯mg of thifluzamide kg-1 soil for 7, 14, 21, and 28â¯d (biomarker indicators) and 30â¯d (reproduction). Growth and reproduction were inhibited by exposure to thifluzamide at 10.0â¯mg/kg, and the activities of succinate dehydrogenase (SDH) and respiratory chain complex II were inhibited by exposure to 1.0 and 10.0â¯mg/kg thifluzamide for the majority of the 28-d experiment. Reactive oxygen species (ROS) increased across all thifluzamide treatments, and the activities of superoxide dismutase (SOD) and glutathione-S-transferase (GST) tended to be inhibited by thifluzamide. Upon exposure to thifluzamide, the activities of catalase (CAT) and guaiacol peroxidase (POD) initially increased and then decreased. Increased levels of malondialdehyde (MDA) were detected only at seven days after exposure, and genotoxicity increased as the thifluzamide concentration increased. The results suggest that thifluzamide presents a potential risk to earthworms at the concentration of 10.0â¯mg/kg, and its use should be moderated to reduce damage to soil ecosystem function.
Subject(s)
Anilides/toxicity , Oligochaeta/drug effects , Pesticides/toxicity , Soil Pollutants/toxicity , Thiazoles/toxicity , Anilides/analysis , Animals , Antioxidants/metabolism , DNA Damage , Environmental Biomarkers/drug effects , Oligochaeta/growth & development , Oligochaeta/metabolism , Oligochaeta/physiology , Oxidative Stress/drug effects , Pesticides/analysis , Reproduction/drug effects , Soil Pollutants/analysis , Thiazoles/analysisABSTRACT
Children with autistic spectrum disorder (ASD) often exhibit uncontrollable disruptive behaviour during transfer to the operating room and operating table and at the induction of anaesthesia (sleep). This process often involves the physical restraining of children. These children are then lifted onto the operating table by healthcare staff after being anaesthetized. This predisposes children to fall risk and hospital staff to musculoskeletal injuries. We developed two concept mobility devices, IMOVE-I and -II, based on robotics systems comprising of restraint modules and multi-positional modality (sitting, supine, Trendelenburg). The aim was to intuitively secure children to facilitate the safe induction of sleep and ease of transfer onto operating tables upon sleep. IMOVE-I loads the child in standing position using a dual arm restraint module that is activated by trained healthcare staff. IMOVE-II loads the child in the sitting position by motivating the self-application of restraints. Opinions were obtained from 21 operating theatre healthcare staff with experience in the care of ASD children and parents with ASD children. The mean satisfaction rating of IMOVE-I was 5.62 (95% CI 5.00, 6.27) versus 8.10 (95% CI 7.64, 8.55) in IMOVE-II, p < 0.001. IMOVE-II is favoured over IMOVE-I in system operation and safety, ease of use and module functionality.
Subject(s)
Anesthesia , Autism Spectrum Disorder , Child , Disabled Children , Humans , Parents , Sitting PositionABSTRACT
BACKGROUND: In recent years, the rapid development of mobile medical technology has provided multiple ways for the long-term management of chronic diseases, especially diabetes. As a new type of management model, smartphone apps are global, convenient, cheap, and interactive. Although apps were proved to be more effective at glycemic control, compared with traditional computer- and Web-based telemedicine technologies, how to gain a further and sustained improvement is still being explored. OBJECTIVE: The objective of this study was to investigate the effectiveness of an app-based interactive management model by a professional health care team on glycemic control in Chinese patients with poorly controlled diabetes. METHODS: This study was a 6-month long, single-center, prospective randomized controlled trial. A total of 276 type 1 or type 2 diabetes patients were enrolled and randomized to the control group (group A), app self-management group (group B), and app interactive management group (group C) in a 1:1:1 ratio. The primary outcome was the change in glycated hemoglobin (HbA1c) level. Missing data were handled by multiple imputation. RESULTS: At months 3 and 6, all 3 groups showed significant decreases in HbA1c levels (all P<.05). Patients in the app interactive management group had a significantly lower HbA1clevel than those in the app self-management group at 6 months (P=.04). The average HbA1c reduction in the app interactive management group was larger than that in the app self-management and control groups at both months 3 and 6 (all P<.05). However, no differences in HbA1c reduction were observed between the app self-management and control groups at both months 3 and 6 (both P>.05). Multivariate line regression analyses also showed that the app interactive management group was associated with the larger reduction of HbA1c compared with groups A and B at both months 3 and 6 (all P>.05). In addition, the app interactive management group had better control of triglyceride and high-density lipoprotein cholesterol levels at both months 3 and 6 compared with baseline (both P<.05). CONCLUSIONS: In Chinese patients with poorly controlled diabetes, it was difficult to achieve long-term effective glucose improvement by using app self-management alone, but combining it with interactive management can help achieve rapid and sustained glycemic control. TRIAL REGISTRATION: ClinicalTrials.gov NCT02589730; https://clinicaltrials.gov/ct2/show/NCT02589730.
Subject(s)
Diabetes Mellitus, Type 1/prevention & control , Diabetes Mellitus, Type 2/prevention & control , Self-Management , Smartphone , Telemedicine , Asian People , Blood Glucose , China , Diabetes Mellitus, Type 1/blood , Diabetes Mellitus, Type 2/blood , Female , Glycated Hemoglobin/analysis , Humans , Male , Middle Aged , Prospective Studies , Software , Treatment OutcomeABSTRACT
Bile acid (BA) signaling regulates fatty acid metabolism. BA dysregulation plays an important role in the development of metabolic disease. However, BAs in relation to fatty acids have not been fully investigated in obesity-related metabolic disorders. A targeted metabolomic measurement of serum BA and free fatty acid profiles was applied to sera of 381 individuals in 2 independent studies. The results showed that the ratio of dihomo-γ-linolenic acid (DGLA) to deoxycholic acid (DCA) species (DCAS) was significantly increased in obese individuals with type 2 diabetes (T2DM) from a case-control study and decreased in the remission group of obese subjects with T2DM after metabolic surgery. The changes were closely associated with their metabolic status. These results were consistently confirmed in both serum and liver of mice with diet-induced obesity, implying that such a metabolic alteration in circulation reflects changes occurring in the liver. In vitro studies of human liver L-02 cell lines under BA treatment revealed that DCA and its conjugated form, TDCA, significantly inhibited mRNA expression of fatty acid transport protein 5 in the presence of DGLA, which was involved in hepatocyte DGLA uptake. Thus, the DGLA:DCAS ratio may be a promising biomarker for metabolic abnormalities in obesity.-Lei, S., Huang, F., Zhao, A., Chen, T., Chen, W., Xie, G., Zheng, X., Zhang, Y., Yu, H., Zhang, P., Rajani, C., Bao, Y., Jia, W., Jia, W. The ratio of dihomo-γ-linolenic acid to deoxycholic acid species is a potential biomarker for the metabolic abnormalities in obesity.
Subject(s)
8,11,14-Eicosatrienoic Acid/metabolism , Deoxycholic Acid/metabolism , Obesity/blood , Adult , Animals , Biomarkers , Cell Line , Deoxycholic Acid/chemistry , Diet, High-Fat/adverse effects , Female , Glucose Tolerance Test , Hepatocytes/metabolism , Humans , Insulin Resistance , Male , MiceABSTRACT
Endogenous fatty acid metabolism that results in elongation and desaturation lipid products is thought to play a role in the development of type 2 diabetes mellitus (T2DM). In this study, we evaluated the potential of estimated elongase and desaturase activities for use as predictive markers for T2DM remission after Roux-en-Y gastric bypass (RYGB). The results of a targeted metabolomics approach from 2 independent studies were used to calculate 24 serum FA concentration ratios (product/precursor). Gene expression data from an open public data set was also analyzed. In a longitudinal study of 38 obese diabetic patients with RYGB, we found higher baseline stearic acid/palmitic acid (S/P) ratio. This ratio reflects an elovl6-encoded elongase enzyme activity that has been found to be associated with greater possibility for diabetes remission after RYGB [odds ratio, 2.16 (95% CI 1.10-4.26)], after adjustment for age, gender, body mass index, diabetes duration, glycosylated hemoglobin A1c, and fasting C-peptide. Our results were validated by examination of postsurgical elovl6 gene expression in morbidly obese patients. The association of S/P with the metabolic status of obese individuals was further validated in a cross-sectional cohort of 381 participants. In summary, higher baseline S/P was associated with greater probability of diabetes remission after RYGB and may serve as a diagnostic marker in preoperative patient assessment. - Zhao, L., Ni, Y., Yu, H., Zhang, P., Zhao, A., Bao, Y., Liu, J., Chen, T., Xie, G., Panee, J., Chen, W., Rajani, C., Wei, R., Su, M., Jia, W., Jia, W. Serum stearic acid/palmitic acid ratio as a potential predictor of diabetes remission after Roux-en-Y gastric bypass in obesity.
Subject(s)
Diabetes Mellitus/blood , Gastric Bypass , Obesity/surgery , Palmitic Acid/blood , Stearic Acids/blood , Acetyltransferases/genetics , Acetyltransferases/metabolism , Adult , Aged , Biomarkers/blood , Diabetes Mellitus/epidemiology , Fatty Acid Elongases , Female , Humans , Male , Middle Aged , Obesity/blood , Obesity/complicationsABSTRACT
A compound eye and retina-like combination sensor based on a space-variant curved micro lens array (CMLA) is proposed to simultaneously offer the large FOV characteristic of a compound eye and retina-like feature of a single aperture eye. The mathematical models of the sensor are developed and the structure parameters of the space-variant CMLA are deduced. Modeling verification is carried out and the results show that the whole field of view (FOV) of the sensor is 105° and the optical information loss rate is 0.06 when the sector is 32. Imaging simulations illustrate that the sensor possesses the retina-like property, i.e., logarithmic-polar transformation. Meanwhile, the simulation results indicate that the overlapping angles between the two micro lenses on the adjacent rings can be reduced by decreasing the rings and the blind radius, and increasing the sectors. This work is beneficial for large FOV and time-efficient applications.
Subject(s)
Biomimetic Materials , Compound Eye, Arthropod , Lens, Crystalline , Models, Theoretical , Retina , Visual Fields , Animals , Compound Eye, Arthropod/anatomy & histology , Compound Eye, Arthropod/physiology , Equipment Design , Lens, Crystalline/anatomy & histology , Lens, Crystalline/physiology , Retina/anatomy & histology , Retina/physiology , Simulation Training , Visual PerceptionABSTRACT
In the streak tube laser imaging system, there are two conflicts: the first is between high spatial resolution and wide field of view (FOV). The second is between high temporal resolution and deep depth of field (DOF). In this paper, a new non-scanning streak tube laser imaging system is presented. A microlens array with three different apertures is used to non-uniformly collect data from the image plane so the conflict between high spatial resolution and wide FOV is relieved and the detectable range of system is also increased. A remapping fiber optics with special design is used to realign the image plane on the two photocathodes of streak tubes to realize the operation mode of the two streak tubes so the conflict between high temporal resolution and deep DOF is relieved. The mathematical model of the entire imaging system is established based on the range equation. The structure parameters of the receiving optical system are optimized in order to achieve the optimal utilization rate of light energy. In the third, three simulated contrast experiments are organized, and the experiment results demonstrate that the imaging system proposed in this paper possesses properties of higher spatial resolution, wider FOV, higher temporal resolution, deeper DOF, and larger detectable range.
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The 72-hour fast test is the current standard for the diagnosis of insulinoma. However, to conduct this test patients require hospitalization due to the chance of severe hypoglycemic episodes. Thus, it is costly and stressful for the patient. An out-patient test would serve the patient better and be more economical. Our aim was to evaluate the value of insulin to glucose and C-peptide to glucose ratios during a prolonged 5-hour oral glucose tolerance test (5-hour OGTT) in qualitative diagnosis of insulinoma, and to identify the optimal threshold for clinical screening. Initially, 15 subjects with pathological insulinoma and 12 control subjects with reactive hypoglycemia were enrolled in the study. A further 75 subjects with symptoms of hypoglycemia as a chief complaint at their initial clinic visit were subsequently screened. Serum insulin, C- peptide levels and blood glucose were quantified after a 5-hour OGTT in all participants and the ratios of serum concentrations of insulin and C-peptide to glucose were calculated. Subjects with insulinoma had significantly different insulin-to-glucose and C-peptide-to-glucose ratios from reactive hypoglycemia at the times of fasting, 4-hour post glucose load and 5-hour post glucose load. Higher specificity (73.08%) and sensitivity (82.67%) were achieved with the combined insulin-to-glucose ratio at the 5-hour post load and the C-peptide-to-glucose ratio at fasting. In combination, ratios of insulin and C-peptide release relative to blood glucose levels, measured during a 5-hour OGTT, may have important clinical value in the diagnosis of insulinoma.
Subject(s)
Blood Glucose/analysis , C-Peptide/blood , Insulin/blood , Insulinoma/diagnosis , Pancreatic Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Diagnostic Techniques, Endocrine , Female , Glucose Tolerance Test/methods , Humans , Insulinoma/blood , Male , Middle Aged , Pancreatic Neoplasms/blood , Time FactorsABSTRACT
BACKGROUND: Recent studies highlight a negative association between total bilirubin concentrations and albuminuria in patients with type 2 diabetes mellitus. Our study evaluated the relationship between bilirubin concentrations and the prevalence of diabetic nephropathy (DN) in Chinese patients with type 1 diabetes mellitus (T1DM). METHODS: A total of 258 patients with T1DM were recruited and bilirubin concentrations were compared between patients with or without diabetic nephropathy. Multiple stepwise regression analysis was used to examine the relationship between bilirubin concentrations and 24 h urinary microalbumin. Binary logistic regression analysis was performed to assess independent risk factors for diabetic nephropathy. Participants were divided into four groups according to the quartile of total bilirubin concentrations (Q1, 0.20-0.60; Q2, 0.60-0.80; Q3, 0.80-1.00; Q4, 1.00-1.90 mg/dL) and the chi-square test was used to compare the prevalence of DN in patients with T1DM. RESULTS: The median bilirubin level was 0.56 (interquartile: 0.43-0.68 mg/dL) in the DN group, significantly lower than in the non-DN group (0.70 [interquartile: 0.58-0.89 mg/dL], P < 0.001). Spearman's correlational analysis showed bilirubin concentrations were inversely correlated with 24 h urinary microalbumin (r = -0.13, P < 0.05) and multiple stepwise regression analysis showed bilirubin concentrations were independently associated with 24 h urinary microalbumin. In logistic regression analysis, bilirubin concentrations were significantly inversely associated with nephropathy. In addition, in stratified analysis, from the first to the fourth quartile group, increased bilirubin concentrations were associated with decreased prevalence of DN from 21.90% to 2.00%. CONCLUSION: High bilirubin concentrations are independently and negatively associated with albuminuria and the prevalence of DN in patients with T1DM.
Subject(s)
Albuminuria/blood , Bilirubin/blood , Diabetes Mellitus, Type 1/blood , Diabetic Nephropathies/blood , Adult , Aged , Albuminuria/epidemiology , Albuminuria/etiology , Asian People , China/epidemiology , Cross-Sectional Studies , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/epidemiology , Diabetic Nephropathies/epidemiology , Diabetic Nephropathies/etiology , Female , Humans , Logistic Models , Male , Middle Aged , Multivariate Analysis , PrevalenceABSTRACT
Roux-en-Y gastric bypass (RYGB) is one of the most effective treatments for long-term weight loss and diabetes remission; however, the mechanisms underlying these changes are not clearly understood. In this study, the serum metabolic profiles of 23 remission and 12 nonremission patients with type 2 diabetes mellitus (T2DM) were measured at baseline, 6- and 12-months after RYGB. A metabolomics analysis was performed based on ultra-performance liquid chromatography-mass spectrometry. Clinical improvements in insulin sensitivity, energy metabolism, and inflammation were related to metabolic alterations of free fatty acids (FFAs), acylcarnitines, amino acids, bile acids, and lipids species. Differential metabolic profiles were observed between the two T2DM subgroups, and patients with severity fat accumulation and oxidation stress may be more suitable for RYGB. Baseline levels of tryptophan, bilirubin, and indoxyl sulfate measured prior to surgery as well as levels of FFA 16:0, FFA 18:3, FFA 17:2, and hippuric acid measured at 6 months after surgery best predicted the suitability and efficacy of RYGB for patients with T2DM. These metabolites represent potential biomarkers that may be clinically helpful in individualized treatment for T2DM patients by RYGB.
Subject(s)
Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/surgery , Gastric Bypass , Metabolomics , Obesity, Morbid/diagnosis , Obesity, Morbid/surgery , Adult , Amino Acids/blood , Bile Acids and Salts/blood , Bilirubin/blood , Biomarkers/blood , Carnitine/analogs & derivatives , Carnitine/blood , Chromatography, High Pressure Liquid/methods , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Energy Metabolism , Fatty Acids, Nonesterified/blood , Female , Hippurates/blood , Humans , Indican/blood , Insulin Resistance , Male , Mass Spectrometry , Middle Aged , Obesity, Morbid/blood , Obesity, Morbid/complications , Oxidative Stress , Prognosis , Remission Induction , Treatment Outcome , Tryptophan/blood , Weight LossABSTRACT
The integrated model of echo laser pulse profile (ELPP) of a target with arbitrary shape is studied under the condition of the ELPP affected by target and atmospheric turbulence simultaneously. The ELPPs of four typical targets (a plane, a cone, a sphere and an aspherical surface) are employed to test the validity of the model by analytical and numerical approaches. Based on simulations of the ELPP under different targets and atmospheric turbulence intensity, the results show a good agreement between two methods, and the ELPP of a target with discontinuous surface is more easily affected by atmospheric turbulence than that with a continuous surface. Besides that, we study the relationship between the number of grids and the relative error of analytical and numerical approaches, which are of interest to obtain the optimal number of grids used in the simulations.
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A space-variant lens array on a curved surface (SVLACS) with a large field of view is proposed to decrease the size and improve the performance of a space-variant lens array on a plane (SVLAP). The whole mathematical models are developed and tested, and comparative simulations between SVLACS and SVLAP are carried out. Under the identical simulated situations, the radius of SVLACS decreases to 58% of SVLAP. Meanwhile, the performance of optical information loss rate is improved from 0.22 to 0.08. The results are beneficial for designing a retina-like image sensor based on SVLACS.
ABSTRACT
Expression of bone morphogenetic protein 4 (BMP4) in adipocytes of white adipose tissue (WAT) produces "white adipocytes" with characteristics of brown fat and leads to a reduction of adiposity and its metabolic complications. Although BMP4 is known to induce commitment of pluripotent stem cells to the adipocyte lineage by producing cells that possess the characteristics of preadipocytes, its effects on the mature white adipocyte phenotype and function were unknown. Forced expression of a BMP4 transgene in white adipocytes of mice gives rise to reduced WAT mass and white adipocyte size along with an increased number of a white adipocyte cell types with brown adipocyte characteristics comparable to those of beige or brite adipocytes. These changes correlate closely with increased energy expenditure, improved insulin sensitivity, and protection against diet-induced obesity and diabetes. Conversely, BMP4-deficient mice exhibit enlarged white adipocyte morphology and impaired insulin sensitivity. We identify peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC1α) as the target of BMP signaling required for these brown fat-like changes in WAT. This effect of BMP4 on WAT appears to extend to human adipose tissue, because the level of expression of BMP4 in WAT correlates inversely with body mass index. These findings provide a genetic and metabolic basis for BMP4's role in altering insulin sensitivity by affecting WAT development.
Subject(s)
Adipose Tissue, Brown/metabolism , Adipose Tissue, White/metabolism , Bone Morphogenetic Protein 4/genetics , Bone Morphogenetic Protein 4/metabolism , Energy Metabolism , Glucose/metabolism , Homeostasis , 3T3-L1 Cells , Activating Transcription Factor 2/metabolism , Adipocytes, Brown/drug effects , Adipocytes, Brown/metabolism , Adipocytes, Brown/pathology , Adipocytes, White/drug effects , Adipocytes, White/enzymology , Adipocytes, White/pathology , Adipose Tissue, Brown/drug effects , Adipose Tissue, Brown/pathology , Adipose Tissue, Brown/ultrastructure , Adipose Tissue, White/drug effects , Adipose Tissue, White/enzymology , Adipose Tissue, White/ultrastructure , Animals , Diet, High-Fat , Energy Metabolism/drug effects , Fatty Acid-Binding Proteins/metabolism , Gene Expression Regulation/drug effects , Homeostasis/drug effects , Humans , Insulin/pharmacology , Mice , Mice, Inbred C57BL , Mice, Transgenic , Mitochondria/metabolism , Mitochondria/ultrastructure , Organ Size/drug effects , Oxygen Consumption/drug effects , Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha , Phenotype , Thinness/metabolism , Thinness/pathology , Trans-Activators/metabolism , Transcription Factors , p38 Mitogen-Activated Protein Kinases/metabolismABSTRACT
BACKGROUND: Associations between demographic data and pulmonary function have not been adequately examined in patients that underwent Roux-en-Y Gastric Bypass (RYGB). This study was designed to examine changes in body fat distribution and metabolic parameters after RYGB and whether these changes correlated with improved lung function. METHODS: A retrospective review of 32 ethnic Chinese with obesity with body mass index (BMI) 28-35 kg/m(2) and type 2 diabetes (T2DM) was conducted, focusing on metabolic outcomes and pulmonary function 6 months after RYGB. RESULTS: Forced expiratory volume during first second (FEV1), percentage of forced expiratory volume during first second (FEV1 [%pred]), forced vital capacity (FVC), and percentage of forced vital capacity (FVC [%pred]) all improved significantly after RYGB. These increases all were negatively correlated with decreases in body weight and visceral fat area (VFA). The improvements of FEV1, FEV1 [%pred] and FVC were also negatively correlated with baseline of body weight and VFA. Furthermore, increases in FEV1 and FVC were independently associated with baseline of VFA (ß = -0.003, P = 0.000; ß = -0.004, P = 0.002, respectively). CONCLUSIONS: The baseline of VFA and weight loss induced by RYGB independently correlated with improved pulmonary function in Chinese patients.
Subject(s)
Diabetes Mellitus, Type 2/surgery , Gastric Bypass , Intra-Abdominal Fat/pathology , Lung/physiopathology , Obesity, Morbid/surgery , Weight Loss/physiology , Adolescent , Adult , Aged , Body Mass Index , China/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/physiopathology , Female , Follow-Up Studies , Gastric Bypass/statistics & numerical data , Humans , Male , Middle Aged , Obesity, Morbid/complications , Obesity, Morbid/epidemiology , Obesity, Morbid/physiopathology , Organ Size , Respiratory Function Tests , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: Diabetic nephropathy is one of the major microvascular complications of diabetes. We investigated the association between urinary Smad3 (usmad3) levels, glomerular hyperfiltration, and the development of nephropathy in patients with type 2 diabetes mellitus (T2DM). METHODS: The usmad3 level was determined by enzyme-linked immunosorbent assay in 245 well-characterised patients with T2DM and 82 healthy control subjects. The associations of the usmad3 level with glomerular hyperfiltration, glucose and lipid profiles, and renal function were evaluated. RESULTS: The usmad3 level was significantly higher in patients with diabetes than in the control group. The level in the hyperfiltration group was higher than that in the normofiltering group, regardless of whether patients were in the normoalbuminuric or the proteinuria groups. Pearson's correlation analysis suggested that the usmad3 level was significantly correlated with age, systolic blood pressure, fasting plasma glucose, insulin, C-peptide, glycated haemoglobin, and estimated glomerular filtration rate (eGFR). A multiple linear stepwise regression analysis revealed that usmad3 levels in patients with T2DM and an eGFR ≥ 90 ml/min/1.73 m(2) were independently and positively correlated with eGFR, whereas in patients with T2DM and eGFR <90 ml/min/1.73 m(2), the levels were independently and negatively correlated with eGFR. CONCLUSIONS: The usmad3 level was significantly correlated with biphasic changes in the GFR (both glomerular hyperfiltration and reduced eGFR) in patients with T2DM. Usmad3 may serve as a novel marker for hyperfiltration and for screening patients with T2DM for nephropathy.