Chin-Sung Chang

The metabolome profiling and pathway analysis in metabolic healthy and abnormal obesity

Objectives:Mechanisms of the development of abnormal metabolic phenotypes among obese population are not yet clear. In this study, we aimed to screen metabolomes of both healthy and subjects with abnormal obesity to identify potential metabolic pathways that may regulate the different metabolic characteristics of obesity.Methods:We recruited subjects with body mass index (BMI) over 25 from the weight-loss clinic of a central hospital in Taiwan. Metabolic healthy obesity (MHO) is defined as without having any form of hyperglycemia, hypertension and dyslipidemia, while metabolic abnormal obesity (MAO) is defined as having one or more abnormal metabolic indexes. Serum-based metabolomic profiling using both liquid chromatography–mass spectrometry and gas chromatography–mass spectrometry of 34 MHO and MAO individuals with matching age, sex and BMI was performed. Conditional logistic regression and partial least squares discriminant analysis were applied to identify significant metabolites between the two groups. Pathway enrichment and topology analyses were conducted to evaluate the regulated pathways.Results:A differential metabolite panel was identified to be significantly differed in MHO and MAO groups, including L-kynurenine, glycerophosphocholine (GPC), glycerol 1-phosphate, glycolic acid, tagatose, methyl palmitate and uric acid. Moreover, several metabolic pathways were relevant in distinguishing MHO from MAO groups, including fatty acid biosynthesis, phenylalanine metabolism, propanoate metabolism, and valine, leucine and isoleucine degradation.Conclusion:Different metabolomic profiles and metabolic pathways are important for distinguishing between MHO and MAO groups. We have identified and discussed the key metabolites and pathways that may prove important in the regulation of metabolic traits among the obese, which could provide useful clues to study the underlying mechanisms of the development of abnormal metabolic phenotypes.

Prevalence and associated factors of sarcopenia and severe sarcopenia in older Taiwanese living in rural community: The Tianliao Old People study 04

The aim of the present study was to show the prevalence and associated factors of sarcopenia and severe sarcopenia in rural community‐dwelling older Taiwanese.

Inverse Relationship Between Central Obesity and Osteoporosis in Osteoporotic Drug Naive Elderly Females: The Tianliao Old People (TOP) Study

To examine the relationship between central obesity and osteoporosis in elderly females in a rural community, a total of 368 ambulatory elderly women were recruited by random sampling during July 2009. Structured questionnaires were completed to survey possible osteoporosis-related risk factors. Subjects were dichotomized into either noncentral obese (waist circumference [WC]<80cm) or central obese subgroups (WC≥80cm) for further analysis. Bone mineral densities were scanned by dual-energy X-ray absorptiometry installed in a mobile bus. Thoracolumbar spine X-ray examination was interpreted by the same radiologist. Of the 365 subjects with completed data, 275 (75.3%) aged women were classified as having osteoporosis based on diagnostic Model III. Compared with the nonosteoporosis subjects, the subjects with osteoporosis had relatively higher mean age, lower body mass index, and a lower percentage of central obesity. Using the binary logistic regression method, central obesity was negatively associated with osteoporosis in all 3 models (odds ratios in the 3 models were 0.348, 95% confidence interval [CI]: 0.130-0.927; 0.444, 95% CI: 0.218-0.905; and 0.415, 95% CI: 0.184-0.936, respectively; p<0.05). Our study suggests that the paradox between central obesity and osteoporosis in elderly women should be of concern and warrants further study.

Central obesity in males affected by a dyslipidemia-associated genetic polymorphism on APOA1/C3/A4/A5 gene cluster

Background:Central obesity is a rising epidemic, and often occurs in parallel with dyslipidemia. Furthermore, enhancement of ectopic fat deposition has been observed in both human studies and animal models of altered lipidemic control. Though APOA1/C3/A4/A5 genetic polymorphisms are associated with dyslipidemia, their effect on central obesity is less known.Method:The anthropometric and metabolic parameters were taken from obese (body mass index (BMI) ⩾25 kg m−2) and non-obese healthy (BMI <25) Taiwanese patients at the initiation weight-loss intervention and 6 months later. The effects of APOA1/C3/A4/A5 genetic polymorphisms were analyzed cross-sectionally and longitudinally. Gender contributions were specifically examined.Patients:Three hundred and ninety-eight participants (obese n=262; non-obese healthy n=136) were recruited in total, and 130 obese patients underwent weight-loss treatments.Results:APOA5 rs662799 minor allele carriage was associated with unfavorable metabolic profiles in obese but not non-obese individuals at baseline. Further analysis identified gender–genotype interactions in waist-hip ratio (WHR), and that one rs662799 minor allele increased 0.032 WHR unit in obese males as analyzed by linear regression adjusted for age, BMI and plasma triglyceride (TG) (95% confidence interval (CI)=0.014–0.050, P=0.001). The rs662799-associated WHR elevation resulted in increased frequency of central obesity (WHR ⩾1.0) in rs662799 carrying obese males as analyzed by binary logistic regression adjusted for age, BMI and plasma TG (odds ratio=6.52, 95% CI=1.87–22.73, P=0.003). In contrast, APOA5 rs662799 and central obesity were no longer correlated 6 months into weight-loss treatments, owing to significant WHR reductions in male rs662799 minor allele carriers (P=0.001). Meanwhile, hypertriglyceridemia was more prevalent in both male and female obese rs662799 minor allele carriers at baseline (males, P=0.034, females, P=0.007).Conclusion:This study highlights the gender-specific and weight-sensitive effects of APOA5 rs662799 on central obesity in Taiwanese individuals, and that these effects are dyslipidemia-independent and weight-loss responsive.

Phosphorylation of glycogen synthase kinase-3β in metabolically abnormal obesity affects immune stimulation-induced cytokine production

Background:Obesity is a severe health problem worldwide, which leads to multiple comorbidities including type 2 diabetes mellitus and cardiovascular diseases. Inflammation has been found to be an important characteristic of adipose tissue in obese subjects. However, obesity is also associated with compromised immune responses to infections and the impact of obesity on immune function has not been fully understood.Subjects/Methods:To clarify the role of obesity in the immune responses, we investigated the Toll-like receptor (TLR)-induced cytokine secretion by leukocytes from obese and lean subjects. We also investigated the relationship between insulin-induced intracellular signaling and cytokine production using peripheral blood mononuclear cells (PBMCs) and a monocytic cell line THP-1.Results:We found decreased TLR-induced interferon-γ, interleukin-6 (IL-6) and tumor necrosis factor-α secretions and elevated IL-10 secretion by leukocytes from obese subjects when compared with lean controls. PBMCs from obese subjects showed enhanced basal Akt and glycogen synthase kinase-3β (GSK-3β) phosphorylation, which did not further increase with insulin and lipopolysaccharide (LPS) stimulation. We also found that LPS-induced IκBα degradation was inhibited in PBMCs from obese subjects. By using THP-1 cells with GSK-3β knockdown or cells treated with hyperinsulinemic and high-fatty acid conditions, we found that LPS-induced nuclear factor κB (NF-κB) activation was inhibited and cyclic adenosine monophosphate response element-binding protein (CREB) activation was enhanced.Conclusions:These findings indicate that GSK-3β is important in the regulation of NF-κB and CREB activation in leukocytes under the metabolic condition of obesity. Our study revealed a key mechanism through which metabolic abnormalities compromise leukocyte functions in people with obesity.

Effects of Age and Body Mass Index on Thoracolumbar Spine X-Ray for Diagnosing Osteoporosis in Elderly Women: Tianliao Old People (TOP) Study 07.

Purpose The aim of this study was to determine the effects of diagnostic discordance with or without a thoracolumbar spine lateral view X-ray in patients with osteoporosis. Methods We randomly enrolled 368 women over 65 years old (74.3 ± 6.0 years) from Tianliao Township in 2009 (response rate: 75.7%). A diagnosis of osteoporosis was confirmed using one of these criteria: (1) a history of non-traumatic fracture, (2) vertebral fractures based on a thoracolumbar spine lateral view X-ray, or (3) a bone mineral density T-score ≤ -2.5 for the total hip, the femoral neck, the lumbar spine, or all 3 sites. The prevalence of osteoporosis in three groups was compared based on Model I (criteria 1+2) vs. Model II (criteria 1+3) vs. Model III (criteria 1+2+3). The role of thoracolumbar X-ray reflected by the diagnostic discordance of osteoporosis between Models II and III was evaluated. Results The overall prevalence of osteoporosis was 78.3% (Model III, age-standardized 78.1%). The diagnostic discordance was 17.4% in the 368 participants. A logistic regression model showed that age was negatively associated with diagnostic discordance (odds ratio [OR] = 0.93, 95% confidence interval [CI]: 0.88–0.98, p < 0.05), but body mass index was positively associated (OR = 1.07, 95% CI: 1.00–1.15, p < 0.05). Conclusions A thoracolumbar spine lateral view X-ray should be added for women ≥ 65 years old or with a body mass index ≥ 25 kg/m2 to minimize the diagnostic discordance in osteoporosis, especially in highly endemic regions.

Relationship between the FRAX® score and falls in community-dwelling middle-aged and elderly people

Objectives Falls is a risk factor for fracture. The FRAX® predicts fractures. Whether the FRAX® is associated with fall in both gender is inconclusive. The aim of our study is to evaluate the association between FRAX scores and falls. Methods The cross-sectional study set from 2009 to 2010 included 1200 community-dwelling people who were systematically sampled in central Taiwan. The 1200 participants (men: 524; women: 676; ≥40 years old) completed questionnaires about socioeconomic status; lifestyle; medical and fall history were completed. FRAX scores with and without bone mineral density (BMD) were calculated by using the Taiwan calculator. Results A total of 19.8% participants fell down. Binary regression models showed that diabetes mellitus history (OR: 1.61; 95% CI: 1.03–2.52), the FRAX without BMD in a continuous major score (OR: 1.06; 95% CI: 1.03–1.09), continuous hip score (OR: 1.11; 95% CI: 1.05–1.16), categorical major score ≥ 10% (OR: 1.81; 95% CI: 1.25–2.61), and categorical hip score ≥ 3% (OR: 1.80; 95% CI: 1.30–2.50) were independent risk factors for falls. FRAX with BMD in a continuous major score (OR: 1.04; 95% CI: 1.02–1.06), continuous hip score (OR: 1.06; 95% CI: 1.02–1.09), categorical major score ≥ 10% (OR: 1.52; 95% CI: 1.09–2.12), and categorical hip score ≥ 3% (OR: 1.53; 95% CI: 1.13–2.09) were also independent risk factors. Conclusions We concluded that FRAX® scores with and without BMD were unanimously correlated with falls in community-dwelling middle-aged and elderly males and females.