Therapeutic potential of small extracellular vesicles derived from lipoma tissue in adipose tissue regeneration—an in vitro and in vivo study

Abstract Objective To explore the adipogenic effects of the small extracellular vesicles derived from the lipoma tissues (sEV-LT), and to find a new cell-free therapeutic approach for adipose tissue regeneration. Methods Adipose tissue-derived stem cells (ADSCs) and small extracellular vesicles derived from the adipose tissues (sEV-AT) were isolated from human adipose tissue, while sEV-LT were isolated from human lipomatous tissue. ADSCs were characterized by using flow cytometric analysis and adipogenic and osteogenic differentiation assays. sEV was identified by electron microscopy, nanoparticle tracking, and western blotting. ADSCs were treated with sEV-LT and sEV-AT, respectively. Fluorescence confocal microscopy was used to investigate whether sEV-LT and sEV-AT could be taken by ADSCs. The proliferation and migration abilities and adipogenic differentiation assay of ADSCs were evaluated by CCK-8 assays, scratch test, and oil red O staining test, and the expression levels of adipogenic-related genes C/EBP-δ, PPARγ2, and Adiponectin in ADSCs were assessed by real-time quantitative PCR (RT-PCR). The sEV-LT and sEV-AT transplantation tubes were implanted subcutaneously in SD rats, and the neotissues were qualitatively and histologically evaluated at 2, 4, 8, and 12 weeks after transplantation. Hematoxylin and eosin (H&E) staining was subsequently used to observe and compare the adipogenesis and angiogenesis in neotissues, while immunohistochemistry was used to examine the expression and the distribution of C/EBP-α, PPARγ, Adiponectin, and CD31 at the 4th week. Results The in vitro experiments showed that both sEV-LT and sEV-AT could be taken up by ADSCs via endocytosis. The scratch experiment and CCK-8 experiment showed that the migration area and proliferation number of ADSCs in sEV-LT group and sEV-AT group were significantly higher than those in the non-sEV group (p < 0.05). Compared with sEV-AT group, sEV-LT group had larger migration area and proliferation number of ADSCs (p < 0.05). Oil red O staining and RT-PCR experiments showed that, compared with the non-sEVs group, the lipid droplets and the mRNA expression levels of adipogenesis-related genes PPARγ2 and Adiponectin of ADSCs in sEV-LT group and sEV-AT group were significantly upregulated (p < 0.05); however, there was no statistical significance in the expression level of C/EBP-δ (p > 0.05). In addition, no significant difference in the amount of lipid droplets and adipogenesis-related genes between the sEV-LT groups and sEV-AT was seen (p > 0.05). At 2, 4, 8, and 12 weeks, the adipocyte area and the number of capillaries in neotissues in the sEV-LT groups and sEV-AT groups were significantly increased compared with the Matrigel group (p < 0.05); however, there was no dramatic difference between sEV-LT groups and sEV-AT groups (p > 0.05). At the 4th week, neotissues in the sEV-LT groups and sEV-AT groups all showed upregulated expression of C/EBP-α, PPARγ, Adiponectin, and CD31 protein, while neotissues in the Matrigel group only showed positive expression of CD31 protein. Conclusions This study demonstrated that sEV-LT exerted promotion effects on adipose tissue regeneration by accelerating the proliferation, migration, and adipogenic differentiation of ADSCs in vitro and recruiting adipocytes and promoting angiogenesis in vivo. The sEV-LT could serve as an alternative cell-free therapeutic strategy for generating adipose tissue, thus providing a promising application prospect in tissue engineering.

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Therapeutic Potential of Small Extracellular Vesicles Derived from Lipoma Tissue in Adipose Tissue Regeneration – An in Vitro and in Vivo Study

10.21203/rs.3.rs-144257/v1 ◽

2021 ◽

Author(s):

Pengyu Hong ◽

Xiaoyang Xu ◽

Xin Hu ◽

Hao Yang ◽

Yue Wu ◽

...

Keyword(s):

Adipose Tissue ◽

Extracellular Vesicles ◽

Tissue Regeneration ◽

Adipogenic Differentiation ◽

Rt Pcr ◽

Significant Difference ◽

Oil Red O Staining ◽

Oil Red O

Abstract Objective To explore the adipogenic effects of the small extracellular vesicles derived from the lipoma tissues (sEV-LT), and to find a new cell-free therapeutic approach for adipose tissue regeneration. Methods Adipose tissue-derived stem cells (ADSCs) and small extracellular vesicles derived from the adipose tissues (sEV-AT) were isolated from human adipose tissue, while sEV-LT were isolated from human lipomatous tissue. ADSCs were characterized by using flow cytometric analysis, adipogenic and osteogenic differentiation assays. sEV was identified by electron microscopy, nanoparticle tracking and western blotting. ADSCs were treated with sEV-LT and sEV-AT, respectively. Fluorescence confocal microscopy were used to investigate whether sEV-LT and sEV-AT could be taken by ADSCs. The proliferation, migration and adipogenic differentiation of ADSCs were compared by CCK-8 assays, scratch test and oil red O staining test, and the expression levels of adipogenic-related genes C/EBP-δ, PPARγ2 and Adiponectin in ADSCs were compared by real-time quantitative PCR (RT-PCR). The sEV-LT and sEV-AT transplantation tubes were implanted subcutaneously in SD rats, and the neotissues were qualitatively and histologically evaluated in 2, 4, 8 and 12 weeks after transplantation. Hematoxylin and eosin (H&E) staining was used to observe and compare the adipogenesis and angiogenesis in neotissues, while immunohistochemistry was used to examine the expression and distribution of C/EBP-α, PPARγ, Adiponectin and CD31 at the 4th week. Results Both sEV-LT and sEV-AT could be taken up by ADSCs via endocytosis in vitro experiments. The scratch experiment and CCK-8 experiment showed that the migration area and proliferation number of ADSCs in sEV-LT group and sEV-AT group were significantly higher than those in the non-sEVs group(p < 0.05). Compared with sEV-AT group, sEV-LT group had larger migration area and proliferation number of ADSCs(p < 0.05). Oil red O staining and RT-PCR experiments showed that, compared with the group without sEVs, the lipid droplets and the mRNA expression levels of adipogenesis-related genes PPARγ2 and Adiponectin of ADSCs in sEV-LT group and sEV-AT group were significantly up-regulated(p < 0.05), while the expression level of C/EBP-δ was not statistically significant compared to the group without sEVs (p > 0.05); Compared with sEV-AT groups, ADSCs in sEV-LT groups showed no statistically significant difference in the amount of lipid droplets and adipogenesis-related genes(p > 0.05). At 2, 4, 8 and 12 weeks, the adipocyte area and the number of capillaries in neotissues in the sEV-LT groups and sEV-AT groups were significantly increased compared with the Matrigel group(p < 0.05); Compared with sEV-AT groups, sEV-LT groups showed no significant difference in adipocyte area and the number of capillaries in neotissues(p > 0.05). At the 4th week, neotissues in the sEV-LT groups and sEV-AT groups all showed positive expression of C/EBP-α, PPARγ, Adiponectin and CD31 protein, while neotissues in the Matrigel group only showed positive expression of CD31 protein. Conclusions This study demonstrated that sEV-LT exerted promotion effects on adipose tissue regeneration by accelerating the proliferation and migration and adipogenic differentiation of ADSCs in vitro, recruiting adipocytes and promoting angiogenesis in vivo. sEV-LT could serve as an alternative cell-free therapeutic strategy for generating adipose tissue, thus providing a promising application prospect in tissue engineering.

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Knockdown of CDC20 Promotes Adipogenesis of Bone Marrow-derived Stem Cells

10.21203/rs.3.rs-1187942/v1 ◽

2021 ◽

Author(s):

Yangge Du ◽

Yunsong Liu ◽

Yongsheng Zhou ◽

Ping Zhang

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Adipose Tissue ◽

Western Blot ◽

Adipogenic Differentiation ◽

Conditional Knockout ◽

Qrt Pcr ◽

Oil Red O Staining ◽

Oil Red O

Abstract Background: Bone is a rigid organ that provides support and physical protection to vital organs of the body. Several bone loss disorders are commonly associated with increased bone marrow adipose tissue. Bone marrow mesenchymal stromal/stem cells (BMSCs) are multipotent progenitors differentiating into osteoblasts, adipocytes, and chondrocytes. CDC20 is a co-activator of APC/C, required for full ubiquitin ligase activity. In our previous study, CDC20 promoted the osteogenic commitment of BMSCs and Cdc20 conditional knockout mice suggested a decline in bone mass. In this study, we investigated the function of CDC20 in the adipogenic differentiation of BMSCs and provided a new clue between adipogenesis and osteogenesis. Methods: Lentivirus containing CDC20 shRNA was used for CDC20 knockdown in hBMSCs. Primary mBMSCs were isolated from Cdc20f/f and Sp7-Cre;Cdc20f/f mice. Adipogenesis was examined by qRT-PCR and western blot analysis of adipogenic regulators, Oil Red O staining and transplantation into nude mice. The CDC20 knockout efficiency was determined through immunochemistry, qRT-PCR and western blot of bone marrow. Accumulation of adiposity was measured through histology and staining of bone sections. Results: CDC20 expression in hBMSCs was significantly decreased during adipogenic differentiation. Knockdown of CDC20 enhanced adipogenic differentiation of hBMSCs in vitro. CDC20-knockdown hBMSCs showed more adipose tissue–like constructs in H&E staining and Oil Red O staining. Sp7-Cre;Cdc20f/f mice presented increased adipocytes in bone marrow compared with control mice. mBMSCs from Sp7-Cre;Cdc20f/f mice exerted upregulated adipogenic differentiation. Conclusions: Our findings showed that knockdown of CDC20 enhanced adipogenesis of h(m)BMSCs in vitro and in vivo. Overall, CDC20 regulated both adipogenesis and osteogenesis of BMSCs, and may lead to the development of new therapeutic target for “fatty bone” and osteoporosis.

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Perspectives for Future Use of Extracellular Vesicles from Umbilical Cord- and Adipose Tissue-Derived Mesenchymal Stem/Stromal Cells in Regenerative Therapies—Synthetic Review

International Journal of Molecular Sciences ◽

10.3390/ijms21030799 ◽

2020 ◽

Vol 21 (3) ◽

pp. 799 ◽

Cited By ~ 7

Author(s):

Joanna Lelek ◽

Ewa K. Zuba-Surma

Keyword(s):

Adipose Tissue ◽

Umbilical Cord ◽

Extracellular Vesicles ◽

Stromal Cells ◽

Tissue Repair ◽

Molecular Mechanisms ◽

Skin Diseases ◽

Differentiation Potential

Mesenchymal stem/ stromal cells (MSCs) represent progenitor cells of various origin with multiple differentiation potential, representing the most studied population of stem cells in both in vivo pre-clinical and clinical studies. MSCs may be found in many tissue sources including extensively studied adipose tissue (ADSCs) and umbilical cord Wharton’s jelly (UC-MSCs). Most of sanative effects of MSCs are due to their paracrine activity, which includes also release of extracellular vesicles (EVs). EVs are small, round cellular derivatives carrying lipids, proteins, and nucleic acids including various classes of RNAs. Due to several advantages of EVs when compare to their parental cells, MSC-derived EVs are currently drawing attention of several laboratories as potential new tools in tissue repair. This review focuses on pro-regenerative properties of EVs derived from ADSCs and UC-MSCs. We provide a synthetic summary of research conducted in vitro and in vivo by employing animal models and within initial clinical trials focusing on neurological, cardiovascular, liver, kidney, and skin diseases. The summarized studies provide encouraging evidence about MSC-EVs pro-regenerative capacity in various models of diseases, mediated by several mechanisms. Although, direct molecular mechanisms of MSC-EV action are still under investigation, the current growing data strongly indicates their potential future usefulness for tissue repair.

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Secreted-Osteopontin Contributes to Brown Adipogenesis In Vitro via a CD44-Dependent Pathway

Hormone and Metabolic Research ◽

10.1055/a-0926-3991 ◽

2019 ◽

Vol 51 (11) ◽

pp. 741-748

Author(s):

Mengxi Wang ◽

Yaoyao Guo ◽

Yumeng Zhou ◽

Wanwan Yuan ◽

Huixia Li ◽

...

Keyword(s):

Lipid Droplets ◽

Biological Activities ◽

Tumor Formation ◽

Brown Adipocyte ◽

Brown Adipocytes ◽

Protein Levels ◽

Infected Cells ◽

Oil Red O Staining ◽

Oil Red O

AbstractOsteopontin (OPN), a secreted glycoprotein, is involved in various pathophysiological processes including immune response, inflammation, tumor formation, and metabolism. OPN exists in 2 forms, secreted-OPN (sOPN) and intracellular-OPN (iOPN). While they might have different biological activities, it remains largely unknown whether sOPN and iOPN induce the differentiation of brown adipocytes. To test this possibility, 3T3-L1 cells were induced by DMI induction with or without recombinant human OPN (rhOPN, 10, 50, 100, 200 μM), respectively. Meanwhile, another batch of 3T3-L1 cells were infected with Ad-GFP-ap2-OPN and followed by DMI differentiation. Subsequently, the infected cells were treated with either anti-CD44 antibody or immunoglobulin G (Ig G). Accumulation of lipid droplets was visualized by Oil red O staining and protein levels were assayed by western blotting analysis. The results showed that sOPN and not rhOPN, notably increased the accumulation of lipid droplets and the expression of brown adipocyte-related genes. Moreover, neutralization of CD44 partially abrogated the effects induced by sOPN. These data demonstrate that sOPN and not rhOPN has the capacity to induce the differentiation of white preadipocytes into brown adipocytes through a CD44-dependent mechanism. The findings might provide a potential target for sOPN to combat obesity.

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Effect of Gambisan on the Inhibition of Adipogenesis in 3T3-L1 Adipocytes

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2013/789067 ◽

2013 ◽

Vol 2013 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Jung Won Kang ◽

Dongwoo Nam ◽

Kun Hyung Kim ◽

Jeong-Eun Huh ◽

Jae-Dong Lee

Keyword(s):

Dna Content ◽

Hormone Sensitive Lipase ◽

Dependent Manner ◽

Rt Pcr ◽

Hormone Sensitive ◽

Ldh Assay ◽

Dose Dependent ◽

Oil Red O Staining ◽

Oil Red O

This study was conducted to explore the antiadipogenic effect and possible mechanism of Gambisan on 3T3-L1 cells. For quality control, Gambisan was standardized by HPLC and the standard compounds ephedrine, epigallocatechin-3-gallate, and caffeine were screened. Cultured 3T3-L1 cells that had been induced to differentiate were treated with various concentrations of Gambisan or its major component extracts (Ephedra intermediaSchrenk,Atractylodes lanceaDC., andThea sinensisL.) for 72 hours for MTT assay to determine cell viability or 10 days for LDH assay, triglyceride assay, DNA content measurement, Oil red O staining, RT-PCR, and western blot. Gambisan significantly inhibited adipogenesis in 3T3-L1 cells by reducing triglyceride contents and lipid accumulation in a dose-dependent manner without obvious cytotoxicity. Viability and DNA content in 3T3-L1 cells treated with Gambisan were significantly higher than cells treated with the major component extracts at every concentration. The anti-adipogenic effects of Gambisan appeared to be mediated by a significant downregulation of the expression of lipoprotein lipase mRNA and PPARγ, C/EBPα, and SREBP-1 protein apart from the expression of hormone-sensitive lipase. Gambisan could act as a possible therapeutic agent for obesity. However, further studies includingin vivoassays and clinical trials are needed to confirm the efficacy, safety and mechanisms of the antiobesity effects of Gambisan.

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Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors

International Journal of Molecular Sciences ◽

10.3390/ijms23010322 ◽

2021 ◽

Vol 23 (1) ◽

pp. 322

Author(s):

Maria N. Evseeva ◽

Maria S. Balashova ◽

Konstantin Y. Kulebyakin ◽

Yury P. Rubtsov

Keyword(s):

Adipose Tissue ◽

Transcription Factors ◽

Metabolic Disorders ◽

Adipogenic Differentiation ◽

In Vivo Studies ◽

Research Review ◽

Treatment And Prevention

Obesity and type 2 diabetes are both significant contributors to the contemporary pandemic of non-communicable diseases. Both disorders are interconnected and associated with the disruption of normal homeostasis in adipose tissue. Consequently, exploring adipose tissue differentiation and homeostasis is important for the treatment and prevention of metabolic disorders. The aim of this work is to review the consecutive steps in the postnatal development of adipocytes, with a special emphasis on in vivo studies. We gave particular attention to well-known transcription factors that had been thoroughly described in vitro, and showed that the in vivo research of adipogenic differentiation can lead to surprising findings.

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Delivery of miR-424-5p via Extracellular Vesicles Promotes the Apoptosis of MDA-MB-231 TNBC Cells in the Tumor Microenvironment

International Journal of Molecular Sciences ◽

10.3390/ijms22020844 ◽

2021 ◽

Vol 22 (2) ◽

pp. 844

Author(s):

Yueyuan Zhou ◽

Yusuke Yamamoto ◽

Fumitaka Takeshita ◽

Tomofumi Yamamoto ◽

Zhongdang Xiao ◽

...

Keyword(s):

Breast Cancer ◽

Overall Survival ◽

Adipose Tissue ◽

Extracellular Vesicles ◽

Stromal Cells ◽

Triple Negative ◽

Intratumoral Administration ◽

Immunosuppressive Microenvironment

Programmed cell death ligand-1 (PD-L1) overexpressed on cancer cells has emerged as a key inhibitor that maintains the immunosuppressive microenvironment through its interaction with the PD-1 receptor in cancer. Here, we demonstrated that miR-424-5p delivery via extracellular vesicles (EVs) derived from adipose tissue-mesenchymal stromal cells (AT-MSCs) partly promotes proinflammation and enhances antitumor cytotoxicity in vitro and in vivo. Triple negative breast cancer (TNBC) exhibits increased expression of PD-L1, and PD-L1 is positively correlated with the overall survival of patients with TNBC. PD-L1 shows relatively higher expression in MDA-MB-231 (MM231) cells and can be downregulated by miR-424-5p. Furthermore, miR-424-5p transported by EVs can increase the secretion of proinflammatory cytokines, decrease the secretion of anti-inflammatory cytokines and promote the apoptosis of tumor cells. The intratumoral administration of miR-424-5p-EVs significantly slowed tumor growth. In conclusion, these results demonstrate that EVs may serve as a delivery system for novel immunotherapies for TNBC through the miR-424-5p/PD-L1 pathway.

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Generation of functional human adipose tissue in mice from primed progenitor cells

10.1101/267427 ◽

2018 ◽

Cited By ~ 1

Author(s):

Raziel Rojas-Rodriguez ◽

Jorge Lujan-Hernandez ◽

So Yun Min ◽

Tiffany DeSouza ◽

Patrick Teebagy ◽

...

Keyword(s):

Adipose Tissue ◽

Progenitor Cells ◽

Adipogenic Differentiation ◽

Human Adipose Tissue ◽

Cyst Formation ◽

Mesenchymal Progenitor Cells ◽

Genes Encoding ◽

Immunocompromised Mice

AbstarctAdipose tissue is used extensively in reconstructive and regenerative therapies, but transplanted fat often undergoes inflammation and cell death, requiring further revision surgery. We report that functional human adipose tissue can be generated from mesenchymal progenitor cells in-vivo, providing an alternative approach to its therapeutic use. We leveraged previous findings that progenitor cells within the vasculature of human adipose tissue robustly proliferate in 3-dimensional culture under proangiogenic conditions. Implantation of these progenitor cells into immunocompromised mice results in differentiation towards non-adipocyte fates, incapable of generating a distinct tissue structure. However, priming of these progenitor cells in-vitro towards adipogenic differentiation results in formation of functional adipose tissue in-vivo. Mechanistically, priming induces the expression of genes encoding specific extracellular matrix and remodeling proteins, and induces extensive vascularization by host blood vessels. In comparison, grafts from adipose tissue obtained by liposuction undergo poor vascularization, adipocyte death, cyst formation, calcification and inefficient adiponectin secretion. Thus, primed mesenchymal adipose tissue progenitors reveal mechanisms of human adipose tissue development, and have potential to improve outcomes in reconstructive and regenerative medicine.

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Isolation and in vitro culture of intramuscular pre-adipocytes from Luxi adult Yellow cattle

Chinese Journal of Agricultural Biotechnology ◽

10.1017/s1479236207001738 ◽

2007 ◽

Vol 4 (3) ◽

pp. 229-232

Author(s):

Wan Rong ◽

Ding Jian ◽

Zhou Zhen-Ming ◽

Ren Li-Ping ◽

Meng Qing-Xiang

Keyword(s):

Lipid Droplets ◽

Morphological Changes ◽

Local Breed ◽

Chinese Adult ◽

Yellow Cattle ◽

Proliferation And Differentiation ◽

Cell Strains ◽

Oil Red O Staining ◽

Oil Red O

AbstractThree Luxi adult Yellow steers were used to isolate and culture intramuscular pre-adipocytes in vitro as well as to examine factors influencing their proliferation and differentiation. The intramuscular pre-adipocytes were taken from adipose tissues within muscles between the sixth and seventh rib and cultured after digestion with collagenase I. The results showed that the separated cell populations were highly homogeneous, proliferative and doubled within 62 h. When the confluent pre-adipocytes were treated with 10 μg/ml insulin and 0.25 μmol/l dexamethasone, small lipid droplets appeared on day 2 and the number of lipid droplets rapidly increased around the nuclei on day 6. Their dynamic morphological changes, growth curve, Oil Red O staining, and reaction to insulin and dexamethasone all verified their pre-adipocyte identity. Under controlled conditions, the intramuscular pre-adipocytes resumed proliferating and differentiating in vitro. Interestingly, the proportion of cultured diploid pre-adipocytes reached more than 90% after six repeated cultures. This study confirms the existence of functionally active pre-adipocytes within the muscles of Chinese adult local breed cattle. These cell strains are a potentially useful model for understanding further the mechanism of intramuscular adipose deposition in tissues, in order to improve beef quality based on Chinese local breed beef cattle.

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Intermittent Hypoxia Composite Abnormal Glucose Metabolism-Mediated Atherosclerosis In Vitro and In Vivo: The Role of SREBP-1

Oxidative Medicine and Cellular Longevity ◽

10.1155/2019/4862760 ◽

2019 ◽

Vol 2019 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Linqin Ma ◽

Jingchun Zhang ◽

Yu Qiao ◽

Xinli Sun ◽

Ting Mao ◽

...

Keyword(s):

Skeletal Muscle ◽

Glucose Metabolism ◽

Intermittent Hypoxia ◽

Control Group ◽

Abnormal Glucose Metabolism ◽

Mrna And Protein Expression ◽

Oil Red O Staining ◽

Oil Red O

Objective. The aim of this study was to establish a 3T3-L1 adipocyte model and ApoE−/− mouse model of intermittent hypoxia (IH) composite abnormal glucose metabolism (AGM) in vitro and in vivo and explore their synergistic damage effect leading to atherosclerosis (AS) and the influence of SREBP-1 signaling molecule-related mechanisms. Methods. Mature 3T3-L1 adipocytes were cultured with complete culture medium containing DEX 1×106 mol/L for 96 h to establish an AGM-3T3-L1 adipocyte model. Then, AGM-3T3-L1 adipocytes were treated with IH for 0 cycles, 2 cycles, 4 cycles, 8 cycles, 16 cycles, and 32 cycles and sustained hypoxia (SH). ApoE−/− mice were treated with high-fat diet and injection of STZ solution to establish an AGM-ApoE−/− mouse model. A total of 16 AGM-ApoE−/− mice were randomly and averagely divided into the normoxic control group (NC) and model group (CIH). AGM-ApoE−/− mice of the CIH group were treated with IH, which meant that the oxygen concentration fell to 10±0.5% in the first 90 seconds of one cycle and then increased to 21±0.5% in the later 90 seconds, continuous for eight hours per day (09 : 00-17 : 00) with a total of eight weeks. Eight C57BL/6J mice were used as the blank control group (Con) which was fed with conventional diet. qPCR and Western blotting were used to detect the expression level of SREBP-1c, FAS, and IRS-1. Oil Red O staining was used to compare the plaque of the aorta among each mouse group. Results. As a result, within 32 cycles of IH, mRNA and protein expression levels of SREBP-1c and FAS in AGM-3T3-L1 adipocytes were elevated with the increase in IH cycles; the mRNA expression of IRS-1 was decreased after IH 32 cycles and lower than that of the SH group. For the study in vivo, Oil Red O staining showed a more obvious AS aortic plaque in the CIH group. After CIH treatment of 4 w and 8 w, fasting blood glucose (FBG) of the NC group and CIH group was higher than that of the Con group, and the insulin level of the CIH group was higher than that of the Con group after IH treatment of 8 w. The expressions of the IRS-1 mRNA level in the aorta, skeletal muscle, and liver of the CIH group were lower than those in the Con group. The mRNA and protein expression of SREBP-1c and its downstream molecule FAS in the aorta, skeletal muscle, and liver significantly enhanced in the CIH group in contrast with those in the Con group. Conclusion. The CIH composite AGM could promote the progress of AS, which might be related to the modulation of the expression of SREBP-1-related molecular pathways.

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