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Extracellular matrix remodelling in obesity and metabolic disorders

Life Metabolism 2023年第4期2卷 7-21页

作者： Vishal Musale David H.Wasserman Li Kang Division of Systems Medicine School of MedicineUniversity of DundeeDundee DD19SYUnited Kingdom Department of Molecular Physiology and Biophysics Mouse Metabolic Phenotyping CenterVanderbilt UniversityNashvilleTN 37235United States

obesity causes extracellular matrix (ECM) remodelling which can develop into serious pathology and fibrosis, having metabolic effects in insulin-sensitive tissues. The ECM components may be increased in response to overnutrition. This review will focus on specific obesity-associated molecular and pathophysiological mechanisms of ECM remodelling and the impact of specific interactions on tissue metabolism. In obesity, a complex network of signalling molecules such as cytokines and growth factors has been implicated in fibrosis. Increased ECM deposition contributes to the pathogenesis of insulin resistance at least in part through the activation of cell surface integrin receptors and CD44 signalling cascades. These cell surface receptors transmit signals to the cell adhesome which orchestrates an intracellular response that adapts to the extracellular environment. Matrix proteins, glycoproteins, and polysaccharides interact through ligand-specific cell surface receptors that interact with the cytosolic adhesion proteins to elicit specific actions. Cell adhesion proteins may have catalytic activity or serve as scaffolds. The vast number of cell surface receptors and the complexity of the cell adhesome have made study of their roles challenging in health and disease. Further complicating the role of ECM-cell receptor interactions is the variation between cell types. This review will focus on recent insights gained from studies of two highly conserved, ubiquitous axes and how they contribute to insulin resistance and metabolic dysfunction in obesity. These are the collagen-integrin receptor-IPP (ILK-PINCH-Parvin) axis and the hyaluronan-CD44 interaction. We speculate that targeting ECM components or their receptor-mediated cell signalling may provide novel insights into the treatment of obesity-associated cardiometabolic complications.

关键词： extracellular matrix fibrosis insulin resistance obesity metabolism

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Intestinal epithelial cell NCoR deficiency ameliorates obesity and metabolic syndrome

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Acta Pharmaceutica Sinica B 2024年第12期14卷 5267-5285页

作者： Shaocong Hou Hengcai Yu Caihong Liu Andrew M.F.Johnson Xingfeng Liu Qian Jiang Qijin Zhao Lijuan Kong Yanjun Wan Xiaowei Xing Yibing Chen Jingwen Chen Qing Wu Peng Zhang Changtao Jiang Bing Cui Pingping Li State Key Laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100050China Diabetes Research Center of Chinese Academy of Medical Sciences Beijing 100730China CAMS Key Laboratory of Molecular Mechanism and Target Discovery of metabolic Disorder and Tumorigenesis Beijing 100050China Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking UniversityBeijing 100191China Division of metabolic and Bariatric Surgery Department of General SurgeryBeijing Friendship HospitalCapital Medical UniversityNational Clinical Research Center for Digestive DiseasesBeijing 100050China The Access to Advanced Health Institute SeattleWashington 98102USA

Nuclear receptor corepressor(NCoR1)interacts with various nuclear receptors and regulates the anabolism and catabolism of *** imbalance in lipid/energy homeostasis is also an important factor in obesity and metabolic syndrome *** this study,we found that the deletion of NCoR1 in intestinal epithelial cells(IECs)mainly activated the nuclear receptor PPARa and attenuated metabolic syndrome by stimulating *** increase in brown adipose tissue thermogenesis was mediated by gut-derived tricarboxylic acid cycle intermediate succinate,whose production was significantly enhanced by PPARa activation in the fed ***,NCoR1 deletion derepressed intestinal LXR,increased cholesterol excretion,and impaired duodenal lipid absorption by decreasing bile acid hydrophobicity,thereby reversing the possible negative effects of intestinal PPARa ***,the simultaneous regulatory effect of intestinal NCoR1 on both lipid intake and energy expenditure strongly suggests that it is a promising target for developing metabolic syndrome treatment.

关键词： Nuclear receptor co-repressor 1 Intestinal epithelium metabolic syndrome PPAR alpha Liver X receptor Thermogenesis Succinate Cholesterol

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obesity,the metabolic Syndrome,and Type 2 Diabetes in Developing Countries:Role of Dietary Fats and Oils

Obesity,the Metabolic Syndrome,and Type 2 Diabetes in Develo...

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作者： Anoop Misra Neha Singhal Lokesh Khurana Department of Diabetes and metabolic Diseases Fortis HospitalVasant Kunj Center for Diabetes Obesityand Cholesterol(C-DOC) Diabetes Foundation(India) Department of Food and Nutrition Lady Irwin College University of Delhi New DelhiINDIA

Developing countries are undergoing rapid nutrition transition concurrent with increases in obesity,the metabolic syndrome,and type 2 diabetes mellitns(T2DM).From a healthy traditional high-fiber,low-fat,lowcalorie diet,a shift is occurring toward increasing consumption of calorie-dense foods containing refined carbohydrates,fats,red meats,and low *** show an increase in the supply of animal fats and increased intake of saturated fatty acid(SFAs)(obtained from coconut oil,palm oil,and ghee[clarified butter]) in many developing countries,particularly in South Asia and South-East *** some South Asian populations, particularly among vegetarians,intake of n-3 polyunsaturated fatty acids(PUFAs)(obtained from flaxseed,

关键词： fats oils diabetes the metabolic syndrome developing countries obesity

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New discoveries in obesity and related metabolic diseases:from bench to bed

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Journal of Molecular Cell Biology 2021年第8期13卷 541-542页

作者： Weiping Jia Department of Endocrinology and Metabolism Shanghai Diabetes InstituteShanghai Key Laboratory of Diabetes MellitusShanghai Clinical Center for DiabetesShanghai Key Clinical Center for Metabolic DiseaseShanghai Jiao Tong University Affiliated Sixth People’s HospitalShanghai 200233China

obesity,and other metabolic diseases including non-alcoholic fatty liver disease(NAFLD),metabolic syndrome(MetS),type 2 diabetes mellitus(T2DM)and its related complications like chronic kidney disease(CKD),and hepatocellular carcinoma(HCC)have led to alarming health and social burdens globally and in China as *** strong links exist among those multifactorial metabolic disorders,there are limited researches on better understanding of their pathogenesis and the provision of effective interventional measures in *** this special issue,we have five researches including three research articles providing new insights into potential mechanisms in the development and possible prevention and treatment therapies of NAFLD,HCC,and CKD,as well as two review articles summarizing multi-omics profiling and future strategies for precision medicine in T2DM,NAFLD,and MetS,and the rapid advances in the field of metabolic surgery in China.

关键词： diseases prevention obesity

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

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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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Sex Effect on obesity Indices and metabolic Outcomes in Patients with Obese Obstructive Sleep Apnea and Type 2 DiabetesAfter Laparoscopic Roux-en-Y Gastric Bypass Surgery:a Preliminary Study

Sex Effect on Obesity Indices and Metabolic Outcomes in Pati...

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中国睡眠研究会第九届学术年会

作者： Huajun Xu Pin Zhang Xiaodong Han Haoyong Yu Jianzhong Di Jianyin Zou Yuyu Wang Yingjun Qian Yinfang Tu Yuqian Bao Hongliang Yi Jian Guan Shankai Yin Weiping Jia Department of Otolaryngology Shanghai Jiao Tong University Affiliated Sixth People's Hospital Department of General Surgery Shanghai Jiao Tong University Department of Endocrinology and Metabolism Shanghai Jiao Tong University Affiliated Sixth People's Hospital Shanghai Diabetes Institute Shanghai Key Laboratory of Diabetes MellitusShanghai Key Clinical Center for Metabolic Disease

＜正＞Background Roux-en-Y gastric bypass（RYGB）surgery is an effective therapy for obstructive sleep apnea（OSA）.However,little attention has been paid to the treatment goals systemat-ically stratified by *** objective of this study was to assess how sex differences affect obesity indices and metabol-ic outcomes after RYGB *** A sleep questionnaire was conducted and medical histories were ***-night

关键词： Obstructive sleep apnea Bariatric surgery obesity Type 2 diabetes Women

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Reductive stressda common metabolic feature of obesity and cancer

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Acta Pharmaceutica Sinica B 2024年第12期14卷 5181-5185页

作者： Man Luo Xiwen Ma Jianping Ye metabolic Disease Research Center Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450052China Institute of Trauma and Metabolism Zhengzhou UniversityZhengzhou 450052China Tianjian Laboratory of Advanced Biomedical Sciences Academy of Medical SciencesZhengzhou UniversityZhengzhou 450052China Zhengzhou Key laboratory of obesity Research Zhengzhou Central Hospital Affiliated to Zhengzhou UniversityZhengzhou 450052China

Reductive stress,characterized by rising level of NADH(nicotinamide adenine dinucleotide)for a status of NADH/NAD^(+)ratio elevation,has been reported in obesity and ***,the mech-anism and significance of reductive stress remain to be established in *** perspective is prepared to address the issue with new insights published *** is used in production of NADPH,gluta-thione,ATP and heat in the classical *** obesity,elevation of NADH/NAD^(+)ratio,likely from overproduction due to substrate overloading,has been found in the liver for insulin resistance and *** evidence demonstrates that the elevation may induce lipogenesis,purine biosynthesis and gluconeogenesis through activation of transcription factors of ChREBP and *** cancer cells,NADH/NAD^(+)elevation under the Warburg effect is primarily derived from decreased NADH consumption in the mitochondrial ***,NRF2 overactivation from gene mu-tation represents another mechanism of NADH/NAD^(+)elevation from NADH production in the cancer *** elevation is required for quick proliferation of cancer cells through induction of biosynthesis of the essential *** appears that the causes of reductive stress are different between obesity and cancer,while its impact in anabolism is similar in the two conditions.

关键词： Reductive stress NADH Cancer obesity Gluconeogenesis Lipogenesis

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metabolic bariatric surgery and type 2 diabetes mellitus:an endocrinologist's perspective

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The Journal of Biomedical Research 2015年第2期29卷 105-111页

作者： Sonali Ganguly Hong Chang Tan Phong Ching Lee Kwang Wei Tham The obesity & metabolic Unit Department of EndocrinologyLIFE CentreSingapore General Hospital

Traditional treatment of T2 DM consisting of modification of diet,an exercise regimen,and pharmacotherapy has problems of poor lifestyle modifications and fail tend of treatment over time,now bariatric surgery is recommended for treatment of obese patients with T2 DM because its great improvements on weight loss and *** this article,effects of bariatric surgery on diabetes and diabetes-related complications are reviewed.

关键词： type 2 diabetes mellitus metabolic bariatric surgery diabetes remission

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Systematical identification of regulatory GPCRs by single-cell trajectory inference reveals the role of ADGRD1 and GPR39 in adipogenesis

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Science China Life Sciences 2025年

作者： Chuan Ye Xuemei Wang Jun Lin Chenyang Wu Yuhua Gao Chenghao Guo Yunxi Liao Ziyan Rao Shaodong Huang Weixuan Chen Ying Huang Jinpeng Sun Dongyu Zhao Changtao Jiang Center of Basic Medical Research Institute of Medical Innovation and ResearchPeking University Third Hospital Department of Physiology and Pathophysiology School of Basic Medical SciencesPeking University Department of Biomedical Informatics School of Basic Medical SciencesPeking University State Key Laboratory of Vascular Homeostasis and Remodeling Peking University Center for obesity and metabolic Disease Research School of Basic Medical SciencesPeking University State Key Laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyPeking University Third Hospital National Clinical Research Center for Obstetrics and Gynecology Peking University Third Hospital Department of Endocrinology and Metabolism Peking University Third Hospital Key Laboratory Experimental Teratology of the Ministry of Education Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesCheeloo College of MedicineShandong University Department of Immunology School of Basic Medical SciencesPeking University

Adipogenesis is the healthy expansion of white adipose tissue (WAT),serving as a compensatory response to maintain metabolic homeostasis in the presence of excess energy in the ***,the identification of novel regulatory molecules in adipogenesis,specifically membrane receptors such as G protein-coupled receptors (GPCRs),holds significant clinical *** receptors can serve as viable targets for pharmaceuticals,offering potential for restoring metabolic homeostasis in individuals with *** utilized trajectory inference methods to analyze three distinct single-nucleus sequencing (sNuc-seq) datasets of adipose tissue and systematically identified GPCRs with the potential to regulate *** verification in primary adipose progenitor cells (APCs) of mice,we discovered that ADGRD1 promoted the differentiation of APCs,while GPR39 inhibits this *** the obese mouse model induced by a high-fat diet(HFD),both gain-of-function and loss-of-function studies validated that ADGRD1 promoted adipogenesis,thereby improving metabolic homeostasis,while GPR39 inhibited adipogenesis,leading to metabolic ***,through the analysis of 2,400 ChIP-seq data and 1,204 bulk RNA-seq data,we found that the transcription factors (TFs) MEF2D and TCF12 regulated the expression of ADGRD1and GPR39,*** study revealed the regulatory role of GPCRs in adipogenesis,providing novel targets for clinical intervention of metabolic dysfunction in obese patients.

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Metabolome and RNA-seq reveal discrepant metabolism and secretory metabolism profile in skeletal muscle between obese and lean pigs at different ages

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Science China Life Sciences 2025年

作者： Liu Guo Junfei Xu Wenyue Zhou Sisi Chen Hanjing Shi Mengmeng Han Zekun Yang Yehui Duan Weijun Pang Yulong Yin Fengna Li Laboratory of Animal Nutritional Physiology and metabolic Process Key Laboratory of Agro-ecological Processes in Subtropical Region Institute of Subtropical Agriculture Chinese Academy of Sciences University of Chinese Academy of Sciences Laboratory of Animal Fat Deposition and Muscle Development College of Animal Science and Technology Northwest A&F University College of Advanced Agricultural Sciences University of Chinese Academy of Sciences

Metabolites and metabolism-related gene expression profiles in skeletal muscle change dramatically under obesity, aging and metabolic disease. Since obese and lean pigs are ideal models for metabolic research. Here, we compared metabolome and transcriptome of Longissimus dorsi(LD) muscle between Taoyuan black(TB, obese) and Duroc(lean) pigs at different ages. We defined the “window phase” of intramuscular fat(IMF) deposition in TB pig, which has significantly higher IMF than Duroc pig. Our results displayed discrepant lipid composition and different expression genes(DEGs) enriched in lipid metabolism, and both metabolome and transcriptome analyses revealed stronger energy expenditure and more active amino acid and protein metabolism in Duroc pig. 10 up-and 51 down-regulated biomarker metabolites with age-and breed-specificity were identified. Potential secretory metabolites, including organic acid(fumaric acid, succinate,malic acid, and gamma-aminobutyric acid), amino acid(L-lysine, and L-glutamic acid), lipid(2-hydroxyisovaleric acid, and L-carnitine) were demonstrated a significant correlation with IMF deposition. Our research highlights the huge difference of metabolic spectrum in skeletal muscle between obese and lean model and muscle-derived secretory metabolites might act as an ambassador of intercellular communication to regulate systematic metabolism.

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