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Rab18 maintains homeostasis of subcutaneous adipose tissue to prevent obesity-induced metabolic disorders

Science China(Life Sciences) 2024年第6期67卷 1170-1182页

作者： Jiaming Liu Liangkui Li Dijin Xu Yuqi Li Tao Chen Yeyang Liu yuqian bao Yan Wang Longyan Yang Peng Li Li Xu State Key Laboratory of Membrane Biology and Tsinghua-Peking Center for Life Sciences Beijing Advanced Innovation Center for Structural BiologySchool of Life SciencesTsinghua UniversityBeijing 100084China Shanghai Qi Zhi Institute Shanghai 200232China Shanghai Key Laboratory of Metabolic Remodeling and Health Institute of Metabolism and Integrative BiologyFudan UniversityShanghai 200438China Tianjian Laboratory of Advanced Biomedical Sciences Zhengzhou UniversityZhengzhou 450001China Department of Physiology School of Basic Medical SciencesGannan Medical UniversityGanzhou 341000China Department of Endocrinology and Metabolism Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s HospitalShanghai 200025China Center for Endocrine Metabolism and Immune Diseases Beijing Luhe HospitalCapital Medical UniversityBeijing 101149China Beijing Key Laboratory of Diabetes Research and Care Beijing 101149China

Metabolically healthy obesity refers to obese individuals who do not develop metabolic *** people store fat in subcutaneous adipose tissue(SAT)rather than in visceral adipose tissue(VAT).However,the molecules participating in this specific scenario remain ***18,a lipid droplet(LD)-associated protein,mediates the contact between the endoplasmic reticulum(ER)and LDs to facilitate LD growth and *** the present study,we show that the protein level of Rab18 is specifically upregulated in the SAT of obese people and ***18 adipocyte-specific knockout(Rab18 AKO)mice had a decreased volume ratio of SAT to VAT compared with wildtype *** subjected to high-fat diet(HFD),Rab18 AKO mice had increased ER stress and inflammation,reduced adiponectin,and decreased triacylglycerol(TAG)accumulation in *** contrast,TAG accumulation in VAT,brown adipose tissue(BAT)or liver of Rab18AKO mice had a moderate increase without ER stress ***18 AKO mice developed insulin resistance and systematic ***18 AKO mice maintained body temperature in response to acute and chronic cold induction with a thermogenic SAT,similar to the counterpart ***,Rab18-deficient 3T3-L1 adipocytes were more prone to palmitate-induced ER stress,indicating the involvement of Rab18 in alleviating lipid ***18 AKO mice provide a good animal model to investigate metabolic disorders such as impaired *** conclusion,our studies reveal that Rab18 is a key and specific regulator that maintains the proper functions of SAT by alleviating lipid-induced ER stress.

关键词： Rab18 subcutaneous adipose tissue(SAT) metabolically healthy obesity(MHO) lipotoxicity ER stress ectopic lipid storage LD-ER contact

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Metabolic surgery in China: present and future

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Journal of Molecular Cell Biology 2021年第8期13卷 594-609页

作者： Yinfang Tu yuqian bao Pin Zhang Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth Peopled HospitalShanghai Diabetes InstituteShanghai Clinical Center of DiabetesShanghai Key Laboratory of Diabetes MellitusShanghai Key Clinical Center for Metabolic DiseaseShanghai 200233China Department of Endocrinology and Metabolism Jinshan District Central Hospital of Shanghai Sixth People's HospitalShanghai 201599China Department of Bariatric and Metabolic Surgery Shanghai Jiao Tong University Affiliated Sixth Peopled HospitalShanghai 200233China

Obesity and its related complications comprise a serious public health problem worldwide,and obesity is increasing in *** surgery is a new type of treatment with unique advantages in weight loss and obesity-related metabolic *** pathogenesis of obesity is complex and not yet fully ***,we review the current efficacy and safety of metabolic surgery,as well as recent progress in mechanistic studies and surgical procedures in *** exciting and rapid advances in this field provide new opportunities for patients with obesity and strike a balance between long-term effectiveness and safety.

关键词： metabolic surgery type 2 diabetes mellitus obesity metabolic syndrome

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Low-carbohydrate diets lead to greater weight loss and better glucose homeostasis than exercise: a randomized clinical trial

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Frontiers of Medicine 2021年第3期15卷 460-471,F0004页

作者： Lingli Cai Jun Yin Xiaojing Ma Yifei Mo Cheng Li Wei Lu yuqian bao Jian Zhou Weiping Jia Department of Endocrinology and Metabolism Shanghai Clinical Center for DiabetesShanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

Lifestyle interventions,including dietary adjustments and exercise,are important for obesity *** study enrolled adults with overweight or obesity to explore whether either low-carbohydrate diet(LCD)or exercise is more effective in metabolism ***-five eligible subjects were randomly divided into an LCD group(n=22)and an exercise group(EX,n=23).The subjects either adopted LCD(carbohydrate intake<50 g/day)or performed moderate-to-vigorous exercise(≥30 min/day)for 3 *** the interventions,LCD led to a larger weight loss than EX(−3.56±0.37 kg vs.−1.24±0.39 kg,P<0.001),as well as a larger reduction in fat mass(−2.10±0.18 kg vs.−1.25±0.24 kg,P=0.007)and waist circumference(−5.25±0.52 cm vs.−3.45±0.38 cm,P=0.008).Both interventions reduced visceral and subcutaneous fat and improved liver steatosis and insulin *** decreased in both two groups,whereas low-density lipoprotein cholesterol increased in the LCD group but decreased in the EX *** glycemic parameters,including serum glycated albumin,mean sensor glucose,coefficient of variability(CV),and largest amplitude of glycemic excursions,substantially declined in the LCD *** CV slightly decreased after *** pilot study suggested that the effects of LCD and exercise are similar in alleviating liver steatosis and insulin *** with exercise,LCD might be more efficient for weight loss and glucose homeostasis in people with obesity.

关键词： low-carbohydrate diet obesity nonalcoholic fatty liver disease continuous glucose monitoring mean sensor glucose

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Decreasing complexity of glucose time series derived from continuous glucose monitoring is correlated with deteriorating glucose regulation

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Frontiers of Medicine 2023年第1期17卷 68-74页

作者： Cheng Li Xiaojing Ma Jingyi Lu Rui Tao Xia Yu Yifei Mo Wei Lu yuqian bao Jian Zhou Weiping Jia Department of Endocrinology and Metabolism Shanghai Jiao Tong University School of Medicine Affiliated Sixth People’s HospitalShanghai Clinical Center for DiabetesShanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai 200233China College of Information Science and Engineering Northeastern UniversityShenyang 110819China

Most information used to evaluate diabetic statuses is collected at a special time-point,such as taking fasting plasma glucose test and providing a limited view of individual’s health and disease *** a new parameter for continuously evaluating personal clinical statuses,the newly developed technique“continuous glucose monitoring”(CGM)can characterize glucose *** calculating the complexity of glucose time series index(CGI)with refined composite multi-scale entropy analysis of the CGM data,the study showed for the first time that the complexity of glucose time series in subjects decreased gradually from normal glucose tolerance to impaired glucose regulation and then to type 2 diabetes(P for trend<0.01).Furthermore,CGI was significantly associated with various parameters such as insulin sensitivity/secretion(all P<0.01),and multiple linear stepwise regression showed that the disposition index,which reflectsβ-cell function after adjusting for insulin sensitivity,was the only independent factor correlated with CGI(P<0.01).Our findings indicate that the CGI derived from the CGM data may serve as a novel marker to evaluate glucose homeostasis.

关键词： complexity of glucose time series continuous glucose monitoring impaired glucose regulation insulin secretion and sensitivity refined composite multi-scale entropy

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Targeted gene panel provides advantages over whole-exome sequencing for diagnosing obesity and diabetes mellitus

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Journal of Molecular Cell Biology 2023年第6期15卷 40-52页

作者： Hairong Yu Haoyong Yu Rong Zhang Danfeng Peng Dandan Yan Yunjuan Gu yuqian bao Weiping Jia Hong Zhang Cheng Hu Shanghai Diabetes Institute Shanghai Key Laboratory of Diabetes MellitusShanghai Clinical Center for DiabetesShanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai 200233China Department of Endocrinology Affiliated Hospital of Nantong UniversityNantong 226001China Institute for Metabolic Disease Fengxian Central Hospital Affiliated to Southern Medical UniversityShanghai 201499China

A small fraction of patients diagnosed with obesity or diabetes mellitus has an underlying monogenic ***,we constructed a targeted gene panel consisting of 83 genes reported to be causative for monogenic obesity or *** performed this panel in 481 patients to detect causative variants and compared these results with whole-exome sequencing(WES)data available for 146 of these *** coverage of targeted gene panel sequencing was significantly higher than that of *** diagnostic yield in patients sequenced by the panel was 32.9%with subsequent WES leading to three additional diagnoses with two novel *** total,178 variants in 83 genes were detected in 146 patients by targeted *** of the 178 variants were missed by WES,although the WES-only approach had a similar diagnostic *** the 335 samples only receiving targeted sequencing,the diagnostic yield was 32.2%.In conclusion,taking into account the lower costs,shorter turnaround time,and higher quality of data,targeted sequencing is a more effective screening method for monogenic obesity and diabetes compared to ***,this approach could be routinely established and used as a first-tier test in clinical practice for specific patients.

关键词： molecular diagnosis monogenic diabetes mellitus monogenic obesity targeted panel whole-exome sequencing

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Effectiveness of quality of care for patients with type 2 diabetes in China:findings from the Shanghai Integration Model(SIM)

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Frontiers of Medicine 2022年第1期16卷 126-138页

作者： Chun Cai Yuexing Liu Yanyun Li Yan Shi Haidong Zou yuqian bao Yun Shen Xin Cui Chen Fu Weiping Jia the SIM Study Group Shanghai Diabetes Institute Shanghai Jiao Tong University Affiliated Sixth People’s HospitalNational Office for Primary Diabetes CareShanghai Technical Center for Diabetes Prevention and Clinical CareShanghai Key Laboratory of Diabetes MellitusDepartment of Endocrinology and MetabolismShanghai Clinical Center for DiabetesShanghai Key Clinical Center for Metabolic DiseaseShanghai 200233China Shanghai Municipal Center for Disease Control&Prevention Shanghai 200336China Shanghai Eye Disease Prevention and Treatment Center/Shanghai Eye Hospital Shanghai Key Laboratory of Ocular Fundus DiseasesShanghai General HospitalShanghai Engineering Center for Visual Science and PhotomedicineShanghai 200040China Shanghai Municipal Health Commission Information Center Shanghai 200040China 不详

This cross-sectional study aimed to investigate the quality of care of diabetes in Shanghai,China.A total of 173235 patients with type 2 diabetes in 2017 were included in the *** of risk factors and intermediate outcomes were *** patients had a mean age of 66.43±8.12(standard deviation(SD))years and a mean diabetes duration of 7.95±5.53(SD)*** percentage of patients who achieved the target level for HbA_(1c)(<7.0%)was 48.6%.Patients who achieved the target levels for blood pressure(BP)<130/80 mmHg and low-density lipoprotein-cholesterol(LDL-c)<2.6 mmol/L reached 17.5%and 34.0%,respectively.A total of 3.8%achieved all three target levels,and the value increased to 6.8%with an adaptation of the BP target level(<140/90 mmHg)for those over 65 *** analysis identified the factors associated with a great likelihood of achieving all three target levels:male,young age,short diabetes duration,low body mass index,macrovascular complications,no microvascular complications,prescribed with lipid-lowering medication,and no prescription of antihypertensive *** conclusion,nearly 50%and one-third of the patients with diabetes met the target levels for HbA_(1c)and LDL-c,respectively,with a low percentage achieving the BP target *** percentage of patients who achieved all three target levels needs significant improvement.

关键词： type 2 diabetes quality of care macrovascular complication microvascular complication treatment pattern epidemiology

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Sex-and age-specific associations between abdominal fat and non-alcoholic fatty liver disease:a prospective cohort study

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Journal of Molecular Cell Biology 2023年第11期15卷 33-42页

作者： Hongli Chen Yuexing Liu Dan Liu Yebei Liang Zhĳun Zhu Keqing Dong Huating Li yuqian bao Jiarui Wu Xuhong Hou Weiping Jia Department of Endocrinology and Metabolism Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai Key Clinical Center for Metabolic DiseaseShanghai 200233China General Practitioner Teams in Community Health Service Center of Nicheng Pudong New Area DistrictShanghai 201306China CAS Key Laboratory of Systems Biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China

Obesity is closely related to non-alcoholic fatty liver disease(NAFLD).Although sex differences in body fat distribution have been well demonstrated,little is known about the sex-specific associations between adipose tissue and the development of *** community-based cohort data,we evaluated the associations between magnetic resonance imaging quantified areas of abdominal adipose tissue,including visceral adipose tissue(VAT)and subcutaneous adipose tissue(SAT),and incident NAFLD in 2830 participants(1205 males and 1625 females)aged 55–70 *** a 4.6-year median follow-up,the cumulative incidence rates of NAFLD increased with areas of VAT and SAT both in males and in *** analyses showed that the abovementioned positive associations were stronger in males than in females,especially in participants under 60 years *** contrast,these sex differences disappeared in those over 60 years ***,the risk of developing NAFLD increased non-linearly with increasing fat area in a sex-specific ***,sex-specific potential mediators,such as insulin resistance,lipid metabolism,inflammation,and adipokines,may exist in the associations between adipose tissue and *** study showed that the associations between abdominal fat and the risk of NAFLD were stratified by sex and age,highlighting the potential need for sex-and age-specific management of NAFLD.

关键词： visceral adipose tissue subcutaneous adipose tissue sex difference NAFLD incidence prospective study

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Relationship between time in range and corneal nerve fiber loss in asymptomatic patients with type 2 diabetes

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Chinese Medical Journal 2022年第16期135卷 1978-1985页

作者： Wejing Zhao Jingyi Lu Lei Zhang Wei Lu Wei Zhu yuqian bao Jjian Zhou 'Department of Endocrinology and Metabolism Shanghai Jiao Tong Universty Ailatede Sith People's HospitalShanghai Cinical Center for DiabetesShanghai Key Clinical Center for Metabolic DiseaseShanghai Diabetes IstuteShanghai Key Laboratory of Diabetes MellitusShanghai 200233China Shanghai Clinical Center for Metabolic Diseases Shanghai Key Laboratory of Diabetes MeliusShanghai Diabetes IstituteShanghai Jiao Tong University Alilatedae Sith People's HospitalShanghai 200233China Department of Endocrinology and Metabolism Jinshan Branch of Shanghai Jiao Tong University Aflatedae Sixth People's HospitalShanghai 201500China

Background: Corneal confocal microscopy (CCM) is a noninvasive technique to detect early nerve damage of diabetic sensorimotor polyneuropathy (DSPN). Time in range (TIR) is an emerging metric of glycemic control which was reported to be associated with diabetic complications. We sought to explore the relationship between TIR and corneal nerve parameters in asymptomatic patients with type 2 diabetes (T2DM).Methods: In this cross-sectional study, 206 asymptomatic inpatients with T2DM were recruited. After 7 days of continuous glucose monitoring, the TIR was calculated as the percentage of time in the glucose range of 3.9 to 10.0 mmol/L. CCM was performed to determine corneal nerve fiber density, corneal nerve branch density, and corneal nerve fiber length (CNFL). Abnormal CNFL was defined as ≤15.30 mm/***: Abnormal CNFL was found in 30.6% (63/206) of asymptomatic subjects. Linear regression analyses revealed that TIR was positively correlated with CCM parameters both in the crude and adjusted models (all P< 0.05). Each 10% increase in TIR was associated with a 28.2% (95% CI: 0.595–0.866,P = 0.001) decreased risk of abnormal CNFL after adjusting for covariates. With the increase of TIR quartiles, corneal nerve fiber parameters increased significantly (allP for trend <0.01). The receiver operating characteristic curve indicated that the optimal cutoff point of TIR was 77.5% for predicting abnormal CNFL in asymptomatic ***: There is a significant independent correlation between TIR and corneal nerve fiber loss in asymptomatic T2DM patients. TIR may be a useful surrogate marker for early diagnosis of DSPN.

关键词： Continuous glucose monitoring Corneal confocal microscopy Time in range Type 2 diabetes

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早期诊断规范监测--《国家基层糖尿病防治管理指南(2018)》血糖测量部分解读

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中华内科杂志 2019年第4期58卷 318-320页

作者：包玉倩上海交通大学附属第六人民医院内分泌代谢科 200233

血糖监测是糖尿病管理的重要组成部分,维持血糖稳定达标可以有效延缓糖尿病慢性并发症的发生和进展。2018年12月中华医学会糖尿病学分会及国家基层糖尿病防治管理办公室发布了《国家基层糖尿病防治管理指南(2018)》,针对基层医疗卫生现... 详细信息

血糖监测是糖尿病管理的重要组成部分,维持血糖稳定达标可以有效延缓糖尿病慢性并发症的发生和进展。2018年12月中华医学会糖尿病学分会及国家基层糖尿病防治管理办公室发布了《国家基层糖尿病防治管理指南(2018)》,针对基层医疗卫生现状,提出了适用于基层医疗机构的血糖测量方式,为广大基层医务人员规范科学开展血糖监测工作提供了依据。

关键词：糖尿病基层医疗机构血糖测量

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糖化血红蛋白:优势犹在,无可替代

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中华糖尿病杂志 2020年第1期12卷 17-20页

作者：包玉倩上海交通大学附属第六人民医院内分泌代谢科上海市糖尿病临床医学中心 200233

糖化血红蛋白1c(HbA1c)自发现以来,一直被公认为是评价降糖疗效的核心指标。尽管在临床实践中,HbA1c的弱点不断被发现,但随着科技的进步,这些问题逐渐得到解决。尤其是标准化检测方法和质量控制体系的建立,为HbA1c的广泛应用提供了保证... 详细信息

糖化血红蛋白1c(HbA1c)自发现以来,一直被公认为是评价降糖疗效的核心指标。尽管在临床实践中,HbA1c的弱点不断被发现,但随着科技的进步,这些问题逐渐得到解决。尤其是标准化检测方法和质量控制体系的建立,为HbA1c的广泛应用提供了保证,目前HbA1c已成为兼具诊断和监测功能的复合型指标。HbA1c变异度与糖尿病慢性并发症的研究以及HbA1c与其他血糖监测指标转换关系的建立,部分弥补了其不能体现血糖波动的不足。因此,HbA1c尽管不够完美,但是其在糖尿病管理中的优势尚不可替代。

关键词：血糖波动糖尿病管理 HbA1c 血糖监测糖尿病慢性并发症糖化血红蛋白监测功能临床实践

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