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Integrative analysis of miRNA and mRNA profiles reveals that gga-miR-106-5p inhibits Adipogenesis by targeting the KLF15 gene in chickens

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Journal of Animal Science and Biotechnology 2022年第6期13卷 1671-1689页

作者： Weihua Tian Xin Hao Ruixue Nie Yao Ling Bo Zhang Hao Zhang Changxin Wu National Engineering Laboratory for Animal Breeding Beijing Key Laboratory for Animal Genetic ImprovementCollege of Animal Science and TechnologyChina Agricultural UniversityBeijing 100193China Sanya Institute of China Agricultural University Hainan 572025 SanyaChina.

Background:Excessive abdominal fat deposition in commercial broilers presents an obstacle to profitable meat quality,feed utilization,and reproduction.Abdominal fat deposition depends on the proliferation of preadipocytes and their maturation into adipocytes,which involves a cascade of regulatory molecules.Accumulating evidence has shown that microRNAs(miRNAs)serve as post-transcriptional regulators of adipogenic differentiation in mammals.However,the miRNA-mediated molecular mechanisms underlying abdominal fat deposition in chickens are still poorly understood.This study aimed to investigate the biological functions and regulatory mechanism of miRNAs in chicken abdominal Adipogenesis.Results:We established a chicken model of abdominal adipocyte differentiation and analyzed miRNA and mRNA expression in abdominal adipocytes at different stages of differentiation(0,12,48,72,and 120 h).A total of 217 differentially expressed miRNAs(DE-miRNAs)and 3520 differentially expressed genes were identified.Target prediction of DE-miRNAs and functional enrichment analysis revealed that the differentially expressed targets were significantly enriched in lipid metabolism-related signaling pathways,including the PPAR signaling and MAPK signaling pathways.A candidate miRNA,gga-miR-106-5p,exhibited decreased expression during the proliferation and differentiation of abdominal preadipocytes and was downregulated in the abdominal adipose tissues of fat chickens compared to that of lean chickens.gga-miR-106-5p was found to inhibit the proliferation and adipogenic differentiation of chicken abdominal preadipocytes.A dual-luciferase reporter assay suggested that the KLF15 gene,which encodes a transcriptional factor,is a direct target of gga-miR-106-5p.gga-miR-106-5p suppressed the posttranscriptional activity of KLF15,which is an activator of abdominal preadipocyte proliferation and differentiation,as determined with gain-and loss-of-function experiments.Conclusions:gga-miR-106-5p functions as an inhibitor of abdominal Adipogenesis by t

关键词： Abdominal fat Adipogenesis Chickens gga-miR-106-5p KLF15 MiRNA

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RNA-seq analysis reveals the critical role of the novel lnc RNA BIANCR in intramuscular Adipogenesis through the ERK1/2 signaling pathway

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Journal of Animal Science and Biotechnology 2023年第3期14卷 917-935页

作者： Xinhao Ma Xinran Yang Dianqi Zhang Wenzhen Zhang Xiaoyu Wang Kuncheng Xie Jie He Chugang Mei Linsen Zan College of Animal Science and Technology Northwest A&F UniversityYanglingShaanxi 712100People’s Republic of China Xi’an Dairy Cow Breeding Center Xi’an Agriculture and Rural BureauXi’anShaanxi 712100People’s Republic of China National Beef Cattle Improvement Center Northwest A&F UniversityYanglingShaanxi 712100People’s Republic of China

Background Long non-coding RNAs(lncRNAs)regulate numerous biological processes,including Adipogenesis.Research on Adipogenesis will assist in the treatment of human metabolic diseases and improve meat quality in livestock,such as the content of intramuscular fat(IMF).However,the significance of lncRNAs in intramuscular Adipogenesis remains unclear.This research aimed to reveal the lncRNAs transcriptomic profiles in the process of bovine intramuscular Adipogenesis and to identify the lncRNAs involved in the Adipogenesis of bovine intramuscular adipocytes.Results In this research,a landscape of lncRNAs was identified with RNA-seq in bovine intramuscular adipocytes at four Adipogenesis stages(0 d,3 d,6 d,and 9 d after differentiation).A total of 7035 lncRNAs were detected,including 3396 novel lncRNAs.Based on the results of differential analysis,co-expression analysis,and functional prediction,we focused on the bovine intramuscular Adipogenesis-associated long non-coding RNA(BIANCR),a novel lncRNA that may have an important regulatory function.The knockdown of BIANCR inhibited proliferation and promoted apoptosis of intramuscular preadipocytes.Moreover,BIANCR knockdown inhibited intramuscular Adipogenesis by regulating the ERK1/2 signaling pathway.Conclusion This study obtained the landscape of lncRNAs during Adipogenesis in bovine intramuscular adipocytes.BIANCR plays a crucial role in Adipogenesis through the ERK1/2 signaling pathway.The results are noteworthy for improving beef meat quality,molecular breeding,and metabolic disease research.

关键词： Adipogenesis BIANCR Bovine Intramuscular adipocyte LncRNAs

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m^(6)A demethylase FTO regulate CTNNB1 to promote Adipogenesis of chicken preadipocyte

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Journal of Animal Science and Biotechnology 2023年第2期14卷 578-592页

作者： Kan Li Weichen Huang Zhijun Wang Qinghua Nie Department of Animal Genetics Breeding and ReproductionCollege of Animal ScienceSouth China Agricultural UniversityGuangzhou 510642China National‑Local Joint Engineering Research Center for Livestock Breeding Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breedingand Key Laboratory of Chicken GeneticsBreeding and ReproductionMinistry of AgricultureGuangzhou 510642China

Background:N6-methyladenosine(m^(6)A)is an abundant post-transcriptional RNA modification that affects various biological processes.The fat mass and obesity-associated(FTO)protein,a demethylase encoded by the FTO gene,has been found to regulate adipocyte development in an m^(6)A-dependent manner in multiple species.However,the effects of the m^(6)A methylation and FTO demethylation functions on chicken Adipogenesis remain unclear.This study aims to explore the association between m^(6)A modification and chicken Adipogenesis and the underlying mechanism by which FTO affects chicken preadipocyte development.Results:The association between m^(6)A modification and chicken lipogenesis was assessed by treating chicken pread-ipocytes with different doses of methyl donor betaine and methylation inhibitor cycloleucine.The results showed that betaine significantly increased methylation levels and inhibited lipogenesis,and the inverse effect was found in preadipocytes after cycloleucine treatment.Overexpression of FTO significantly inhibited m^(6)A levels and promoted proliferation and differentiation of chicken preadipocytes.Silencing FTO showed opposite results.Mechanistically,FTO overexpression increased the expression of catenin beta 1(CTNNB1)by improving RNA stability in an m^(6)A-dependent manner,and we proved that FTO could directly target CTNNB1.Furthermore,CTNNB1 may be a positive regulator of Adipogenesis in chicken preadipocytes.Conclusions:m^(6)A methylation of RNA was negatively associated with Adipogenesis of chicken preadipocytes.FTO could regulate CTNNB1 expression in a demethylation manner to promote lipogenesis.

关键词： Adipogenesis Chicken CTNNB1 FTO m^(6)A

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Long non-coding RNAMIR22HG inhibits the Adipogenesis of human bone marrow mesenchymal stem cells with the involvement of Wnt/β-catenin pathway

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BIOCELL 2022年第7期46卷 1717-1724页

作者： CHANYUAN JIN ZIYAO ZHUANG LINGFEI JIA YUNFEI ZHENG Second Clinical Division Peking University School and Hospital of StomatologyBeijing100081China Department of Orthodontics Peking University School and Hospital of StomatologyBeijing100081China Central Laboratory Peking University School and Hospital of StomatologyBeijing100081China National Center of Stomatology National Clinical Research Center for Oral DiseasesNational Engineering Laboratory for Digital and Material Technology of StomatologyBeijing100081China

Osteoporosis is a frequently occurring bone remodeling disorder worldwide with one characteristic being decreasing bone mineral density and a predisposition to bone fracture,which diminishes patients’quality of life.Several studies showed that imbalance between the osteogenesis and Adipogenesis of bone marrow mesenchymal stem cells(BMSCs)took part in the development of osteoporosis.In previous study,we found MIR22HG regulated the osteogenesis of human BMSCs positively.In this study,we found that MIR22HG was decreased during the Adipogenesis of human BMSCs and exerted negative effects on Adipogenesis with the involvement of Wnt/β-catenin signaling pathway both in vitro and in vivo.Nitazoxanide could inhibit Wnt signaling and relieve MIR22HG’s suppression on Adipogenesis.These findings indicated that MIR22HG had great potential in clinical application for osteoporosis treatment and prevention.

关键词： BMSCs Osteoporosis MIR22HG Adipogenesis Wnt/β-catenin pathway

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Effect of methyl tert-butyl ether on Adipogenesis and glucose metabolism in vitro and in vivo

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Journal of Environmental Sciences 2019年第11期31卷 208-219页

作者： Yue Tang Qidong Ren Qing Wen Caixia Yu Xinni Xie Qing Hu Yuguo Du State Key Laboratory of Environmental Chemistry and Eco-toxicology Research Center for Eco-Environmental Sciences Chinese Academy of Sciences Beijing 100085 China School of Chemical Sciences University of Chinese Academy of Sciences Beijing 100049 China School of Environmental Science and Engineering Southern University of Science and Technology Shenzhen 518055 China

Methyl tert-butyl ether (MTBE),as a widely used gasoline additive,is suspected of being environmentally toxic.MTBE accumulates mainly in adipose tissue,but its effect on obesity or obesity-related metabolic disorders has not been well understood yet.Therefore,we examined the effect of MTBE on the adipose function and the related metabolic processes with both 3T3-L1 cell line and C57BL/6J mice model.We found that exposure to MTBE at the environmental relevant concentration (100 μmol/L) could significantly induce differentiation of preadipocyte and disturb insulin-stimulated glucose uptake of mature adipocyte.The in vivo observation in male mice showed a positive correlation of visceral white adipose tissue (vWAT) expansion and cell size increase with MTBE treatment in 14 weeks.Glucose tolerance and insulin sensitivity tests demonstrated that MTBE at 1000 μg/(kg·day) disturbed the systemic glucose metabolism in a gender-specific manner,which might be partly attributed to the alterations of gut microbiota community at genus level with respect to Akkermansia,Clostridium XIVb,and Megamonas.In summary,our study characterized the effect of MTBE on adipose tissue function and glucose homeostasis in vitro and in vivo,and revealed that systemic disorders of the glucose metabolism might be modulated by the related gut microbiota.

关键词： MTBE Adipogenesis Glucose metabolism Metabolic disorder Gut microbiota

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Cytokines and inflammation in Adipogenesis:an updated review

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Frontiers of Medicine 2019年第3期13卷 314-329页

作者： Ning Jiang Yao Li Ting Shu Jing Wang State Key Laboratory of Medical Molecular Biology Institute of Basic Medical SciencesChinese Academy of Medical SciencesDepartment of PathophysiologyPeking Union Medical CollegeBeijing 100730China

The biological relevance of cytokines is known for more than 20 years.Evidence suggests that Adipogenesis is one of the biological events involved in the regulation of cytokines,and pro-inflammatory cytokines (e.g.,TNFα and IL-1β)inhibit Adipogenesis through various pathways.This inhibitory effect can constrain the hyperplastic expandability of adipose tissues.Meanwhile,chronic low-grade inflammation is commonly observed in obese populations.In some individuals,the impaired ability of adipose tissues to recruit new adipocytes to adipose depots during overnutrition results in adipocyte hypertrophy,ectopic lipid accumulation,and insulin resistance.Intervention studies showed that pro-inflammatory cytokine antagonists improve metabolism in patients with metabolic syndrome.This review focuses on the cytokines currently known to regulate Adipogenesis under physiological and pathophysiological circumstances.Recent studies on how inhibited Adipogenesis leads to metabolic disorders were summarized.Although the interplay of cytokines and lipid metabolism is yet incompletely understood,cytokines represent a class of potential therapeutic targets in the treatment of metabolic disorders.

关键词： cytokines inflammation Adipogenesis type 2 diabetes mellitus metabolic disorder

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Chemerin deficiency regulates Adipogenesis is depot different through TIMP1

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Genes & Diseases 2021年第5期8卷 698-708页

作者： Cheng-Long Huang Liu-Ling Xiao Min Xu Jun Li Shu-Fen Li Cui-Song Zhu Yu-Li Lin Rui He Xi Li Biology Science Institutes Chongqing Medical UniversityChongqing400016PR China Center for Translational Research in Hematologic Malignancies Houston Methodist Cancer CenterHouston Methodist Research InstituteHoustonTX 77030USA Key Laboratory of Metabolic Molecular Medicine The Ministry of EducationDepartment of Biochemistry and Molecular BiologyFudan University Shanghai Medical CollegeShanghai200032PR China Shanghai Public Health Clinical Center Fudan UniversityShanghai201508PR China Department of Immunology Fudan University Shanghai Medical CollegeShanghai200032PR China

Adipocytes and immune cells are vital for the development of adipose tissue.Adi-pokines secreted by adipocytes regulate Adipogenesis and body metabolism.Chemerin is one of the adipokines.However,the function and mechanism of chemerin in adipose tissue are not fully illuminated.Compared with wild type(WT)mice,Rarres2^(-/-)mice gained weight and significantly increased fat distribution in subcutaneous adipose tissue(SAT),rather than visceral adipose tissue(VAT)on high fat diet(HFD).PPARg and C/EBPa,the master regulators of Adipogenesis,were up-regulated in SAT and down-regulated in VAT in Rarres2^(-/-)mice comparing with WT mice.Inspite of chemerin deficiency or not,the ratio of adipocyte-progenitors to total cells and the differentiation capacity of adipocyte-progenitors were similar in SAT and VAT,but macrophage infiltration in VAT was more severe than in SAT in Rarres2^(-/-)mice.Furthermore,CD45þimmune cells supernatant from Rarres2^(-/-)SAT pro-moted the differentiation of adipocyte-progenitors and 3T3-L1 cells.Adipokine array assay of CD45þimmune cells supernatant revealed that metalloproteinase inhibitor 1(TIMP1),an in-hibitor of Adipogenesis,was reduced in Rarres2^(-/-)SAT,but increased in Rarres2^(-/-)VAT.As we specifically knocked down chemerin in SAT,TIMP1 was down-regulated and Adipogenesis was promoted with reducing infiltration of macrophages.The present study demonstrates that the effects of chemerin on adipose tissue is depot different,and specific knock down chemerin in SAT promote Adipogenesis and improve glucose tolerance test(GTT)and insulin tolerance test(ITT).This suggests a potential therapeutic target for chemerin in the treatment of obesity related metabolic disorder.

关键词： Adipogenesis Adipose tissue depot Chemerin Inflammation TIMP1

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Adipogenesis Inhibitory Activity of Hypersampsone P from Hypericum subsessile

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Natural Products and Bioprospecting 2020年第3期10卷 163-170页

作者： Hui-Min Zhou Yan-Song Ye Na-Na Jiang Rong-Fang Mu Qian Wang Jing Hu Xia Liu Wan-Ying Qin Gang Xu Wen-Yong Xiong State Key Laboratory of Phytochemistry and Plant Resources in West China Kunming Institute of BotanyChinese Academy of SciencesKunming 650201YunnanPeople’s Republic of China University of Chinese Academy of Sciences Beijing 100049People’s Republic of China Department of Pharmacy Chongqing Traditional Chinese Medicine HospitalChongqing 400021China

Adamantane polycyclic polyprenylated acylphloroglucinols(PPAPs)with caged architecture,a special class of hybrid natural products,is specifically rich in the plant family Guttiferae,especially Hypericum or Garcinia genus.Hypersampsone P is one of Adamantane PPAPs compounds extracted from Hypericum subsessile.Here we have chosen,screened ten PPAPs and identified one of them showed an activity in inhibiting of adipocytes differentiation.Particularly,the compound,hypersamp-sone P,blunted the adipocyte differentiation dose-dependently.Moreover,hypersampsone P down-regulated the expressions of several key regulators for Adipogenesis,including PPARγand FABP4.The treatment of cells at the early stage of adipo-genesis by hypersampsone P induced the greatest blunting of adipocyte differentiation and the effect might be involved in the LKB1-AMPK signaling pathway.

关键词： Adipogenesis LKB1 AMPK Hypericum subsessile Hypersampsone P

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Korean Chungtaejeon tea extract attenuates weight gain in C57BL/6J-Lep ob/ob mice and regulates Adipogenesis and lipolysis in 3T3-L1 adipocytes

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Journal of Integrative Medicine 2017年第1期15卷 56-63页

作者： Bhesh Raj Sharma Dong Wook Kim Dong Young Rhyu Department of Oriental Medicine Resources and Institute of Korean Medicine Industry Mokpo NationalUniversity Jeonnam 534-729 Republic of Korea

OBJECTIVE： Traditional Korean Chungtaejeon （CTJ） tea is a type of fermented tea, which has received increasing attention in recent years because of its purported health benefits. The present study was designed to investigate the effect and mechanism of CTJ tea extract on body weight gain using C57BL/6J-Lep ob/ob mice and 3T3-L1 adipocytes, respectively. METHODS： The effects of CTJ on cell viability, lipid accumulation, and expression of protein and mRNA were measured in 3T3-L1 adipocytes by using 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide, oil red O staining, Western blotting, and reverse transcriptase-polymerase chain reaction analyses. C57BL6J-Lep ob/ob mice were administered with CTJ （200 or 400 mg/kg body weight） for ten weeks. Then, body weight, food intake, total cholesterol, and triglyceride were measured in ob/ob mice. RESULTS： CTJ tea extract treated at 250 wg/mL （CTJ250） significantly suppressed lipid accumulation in the differentiated 3T3-L1 adipocytes. Likewise, CTJ250 significantly decreased the protein expression of peroxisome proliferator-activated receptor Y （PPARy）, CCJ^u~,T/enhancer-binding protein a, and adipocyte lipid- binding protein, and regulated the mRNA expression of PPART, sterol regulatory element-binding protein- lc gene, fatty acid synthase, adipocyte lipid-binding protein, hormone-sensitive lipase, carnitine palmitoyl transferase 1, cluster of differentiation 36, and acetyl-CoA carboxylase in the differentiated 3T3-L1 adipocytes. Mice administered with CTJ showed dose-dependent decrease in body weight gain, starting from week 4 of the experiment. CTJ tea extract administered at 400 mg/kg body weight significantly decreased fat mass, food efficacy ratio, and levels of plasma triglyceride and total cholesterol. CONCLUSION： CTJ attenuated weight gain in ob/ob mice and regulated the activity of the molecules involved in Adipogenesis and lipolysis in 3T3-L1 adipocytes. CTJ is a potentially valuable herbal therapy for the prevention of obesity and/or obesity-related diso

关键词： Adipogenesis Chungtaejeon lipolysis C57BL/6J-Lep ob/ob mice weight loss

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Calcium carbonate nanoparticles promote osteogenesis compared to Adipogenesis in human bone-marrow mesenchymal stem cells

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Progress in Natural Science:Materials International 2018年第5期28卷 598-608页

作者： Xiaoning Li Xing Yang Xujie Liu Wei He Qianli Huang Shengrong Li Qingling Feng School of Earth Science and Resources China University of Geosciences State Key Laboratory of New Ceramics and Fine Processing School of Materials Science and Engineering Tsinghua University Graduate School at Shenzhen Tsinghua University School of Materials Science and Engineering University of Science and Technology Beijing Key Laboratory of Advanced Materials of Ministry of Education of China School of Materials Science and Engineering Tsinghua University

Rhombohedron-like and fusiform calcium carbonate nanoparticles were fabricated using a new method. Their geometry was controlled by varying the mixing speed and ratio of ethanol versus water in reaction system. The calcium carbonate nanoparticles(CCNPs) have slight effect on viability of human bone-marrow mesenchymal stem cells(hBMSCs) with dose-dependent and shape-dependent, but they can significantly promote osteogenic differentiation of hBMSCs in vitro by 10–37% increase of alkaline phosphatase(ALP) activity, 9–36% growth of collagen secretion and 1.13–1.83 folds upregulation of osteogenesis-related genes, even at lower dose ranges(5–20 μg/ml). The efficacity of promoting osteogenesis depends on the shape and dose of CCNPs. Furthermore,Adipogenesis was inhibited by less accumulation of lipid droplets, lower triglyceride(TG) secretion and downregulation of Adipogenesis-related genes. These findings improve the understanding of effects CCNPs on hBMSCs fate towards osteoblasts or adipocytes and have meaningful impact for combining use of CCNPs and hBMSCs in tissue engineering and regenerative medicine fields.

关键词： Human bone-marrow mesenchymal stem cells Calcium carbonate nanoparticles Osteogenesis Adipogenesis

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