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18. Functional evaluation of the human fat distribution HOXC13 gene locus

Author

Kuo, Feng-Chih, Pinnick, Katherine, and Karpe, Fredrik

Subjects
612.3
Abstract

Gynoid fat distinguishes from android fat in developmental origin and possesses metabolically protective roles, especially in women. Growing evidence supports that epigenetic modifications could potentially explain the regional differences between fat depots. Recent progress in transcriptome analysis has revealed that long non-coding RNAs (lncRNAs) play roles in epigenetic regulation, but their potential functions in fat depot-specific transcription remain largely unexplored. HOX transcript antisense RNA (HOTAIR) is a lncRNA that is expressed exclusively in the gluteal subcutaneous adipose tissue (GSAT); it is undetectable in the abdominal subcutaneous adipose tissue (ASAT) and locates under the fat distribution - genome-wide association studies (GWAS) locus near and around the HOXC13 gene. Therefore, the aim of this project was to investigate the depot-specific functional roles of the HOTAIR gene. GSAT HOTAIR expression was highly variable between individuals but generally expressed at lower levels in females compared with men. Detailed annotation of HOTAIR-haplotype tagging single nucleotide polymorphisms (SNPs) identified the minor allele of rs76084431 as a GSAT HOTAIR expression quantitative trait locus (eQTL) associated with increased android to gynoid fat mass ratio in females. Comparison of histone marks between abdominal and gluteal preadipocytes showed that rs76084431 is positioned in an open chromatin region and which could be considered as a HOTAIR enhancer in gluteal preadipocytes. HOTAIR stable knockdown and constitutive overexpression in human adipocytes provided further evidence that the HOTAIR gene is essential for the gluteal adipocytes, but anti-adipogenic for abdominal adipocytes. Weighted Gene Co-expression Network Analysis (WGCNA) of RNA-seq from HOTAIR knockdown cells data suggested regulation a number of regulated pathways: extracellular matrix and protocadherin genes appear to be predominant HOTAIR downstream pathways in the gluteal preadipocytes. CEBPD, PTEN and PCDH10 were shown to be epigenetically regulated by HOTAIR during adipogenic differentiation of the gluteal preadipocytes. Overall, these data suggest that HOTAIR is a novel and dynamic regulator of the adipocyte epigenome with functional importance for regional human adipose tissues.

Published
2018

30. Osteoporosis as the Female-Specific Risk Factor for Dynapenia in Elderly Patients with Type 2 Diabetes.

Author

Lu, Chieh-Hua, Su, Sheng-Chiang, and Kuo, Feng-Chih

Subjects
DUAL-energy X-ray absorptiometry, TYPE 2 diabetes, OLDER people, LOGISTIC regression analysis, BODY mass index
Abstract

Aims: Dynapenia is a noteworthy health issue contributing to increased risk of falling, but its co-occurrence with osteoporosis in elderly individuals with type 2 diabetes mellitus (T2DM) has not been well explored. Therefore, this study aimed to establish the association between osteoporosis and dynapenia, focusing on T2DM females due to their high prevalence of osteoporosis and fragility. Methods: We conducted a cross-sectional study to recruit a total of 103 T2DM patients (43 males and 60 females), aged between 50 and 80 years with median 68.0 years. Dual-energy X-ray absorptiometry (DXA) and dominant hand grip strength measurements were performed to define body composition, osteoporosis, and dynapenia in a sex-specific manner. Results: Higher prevalence of dynapenia and dyna-osteoporosis was observed in female T2DM patients with a significantly positive correlation between osteoporosis and dynapenia even after adjustment of body mass index (BMI). By performing a multivariate logistic regression analysis, both BMI and osteoporosis were identified as risk predictors for the development of dynapenia in female T2DM patients with odds ratios (95% CIs) of 1.234 (1.029–1.480) and 4.883 (1.352–17.630), respectively. Conclusions: Our results point out there is high, female-specific co-occurrence of osteoporosis and dynapenia in T2DM patients. Moreover, having osteoporosis and increased BMI might boost the risk of dynapenia in elderly females with T2DM. [ABSTRACT FROM AUTHOR]

Published
2024
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43. The role of traditional Chinese medicine on fracture surgery, hospitalization, and total mortality risks in diabetic patients with osteoporosis.

Author

Liu, Yi-Chen, Chung, Chi-Hsiang, Lin, Chien-Jung, Su, Sheng-Chiang, Kuo, Feng-Chih, Liu, Jhih-Syuan, Li, Peng-Fei, Huang, Chia-Luen, Ho, Li-Ju, Chang, Chun-Yung, Lin, Ming-Shiun, Lin, Chih-Ping, Cheng, An-Che, Lee, Chien-Hsing, Hsieh, Chang-Hsun, Hung, Yi-Jen, Liu, Hsin-Ya, Lu, Chieh-Hua, and Chien, Wu-Chien

Subjects
CHINESE medicine, PEOPLE with diabetes, NATIONAL health insurance, OSTEOPOROSIS, PROPENSITY score matching
Abstract

Background: Studies have confirmed that osteoporosis has been considered as one of the complications of diabetes, and the health hazards to patients are more obvious. This study is mainly based on the Taiwan National Health Insurance Database (TNHID). Through the analysis of TNHID, it is shown that the combined treatment of traditional Chinese medicine (TCM) medicine in patients of diabetes with osteoporosis (T2DOP) with lower related risks. Methods: According to the study design, 3131 patients selected from TNHID who received TCM treatment were matched by 1-fold propensity score according to gender, age, and inclusion date as the control group. Cox proportional hazards analyzes were performed to compare fracture surgery, hospitalization, and all-cause mortality during a mean follow-up from 2000 to 2015. Results: A total of 1055/1469/715 subjects (16.85%/23.46%/11.42%) had fracture surgery/inpatient/all-cause mortality of which 433/624/318 (13.83%/19.93%/10.16%) were in the TCM group) and 622/845/397 (19.87%/26.99%/12.68%) in the control group. Cox proportional hazards regression analysis showed that subjects in the TCM group had lower rates of fracture surgery, inpatient and all-cause mortality (adjusted HR = 0.467; 95% CI = 0.225–0.680, P<0.001; adjusted HR = 0.556; 95% CI = 0.330–0.751, P<0.001; adjusted HR = 0.704; 95% CI = 0.476–0.923, P = 0.012). Kaplan-Meier analysis showed that the cumulative risk of fracture surgery, inpatient and all-cause mortality was significantly different between the case and control groups (all log-rank p<0.001). Conclusion: This study provides longitudinal evidence through a cohort study of the value of integrated TCM for T2DOP. More research is needed to fully understand the clinical significance of these results. [ABSTRACT FROM AUTHOR]

Published
2024
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