Pub Date : 2022-12-01DOI: 10.1080/21623945.2022.2084900
Shihua Wang, Meiqian Xu, Xian Xiao, Liping Wang, Zhao Sun, Mei Guan, Robert Chunhua Zhao
Increasing evidence has demonstrated the important roles of exosomes during pancreatic cancer development. However, the effects of pancreatic cancer exosomes (PC-exos) on adipocytes remain largely unknown. Here, we used mass-spectrometry-based lipidomics to identify lipids that were changed in adipocytes after exposure to PC-exos, and we found that triglyceride (TG) reduction was the most significant, which might be induced by increased lipolysis because the number of large lipid droplets increased while small ones decreased. Additionally, abdominal adipocytes in mice injected with PC-exos had a relatively smaller size. Mechanistically, we found that genes involved in metabolism and inflammation were up-regulated, among which increase of IL-6 was significant, and we then found IL-6 promoted lipolysis. To our knowledge, this is the first study on the lipidomics changes of adipocytes after PC-exos treatment.
{"title":"Pancreatic cancer cell exosomes induce lipidomics changes in adipocytes.","authors":"Shihua Wang, Meiqian Xu, Xian Xiao, Liping Wang, Zhao Sun, Mei Guan, Robert Chunhua Zhao","doi":"10.1080/21623945.2022.2084900","DOIUrl":"10.1080/21623945.2022.2084900","url":null,"abstract":"<p><p>Increasing evidence has demonstrated the important roles of exosomes during pancreatic cancer development. However, the effects of pancreatic cancer exosomes (PC-exos) on adipocytes remain largely unknown. Here, we used mass-spectrometry-based lipidomics to identify lipids that were changed in adipocytes after exposure to PC-exos, and we found that triglyceride (TG) reduction was the most significant, which might be induced by increased lipolysis because the number of large lipid droplets increased while small ones decreased. Additionally, abdominal adipocytes in mice injected with PC-exos had a relatively smaller size. Mechanistically, we found that genes involved in metabolism and inflammation were up-regulated, among which increase of IL-6 was significant, and we then found IL-6 promoted lipolysis. To our knowledge, this is the first study on the lipidomics changes of adipocytes after PC-exos treatment.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235897/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40239972","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/21623945.2022.2104509
Wei-En Ho, Lijuan Sun, Hui Jen Goh, Mya Thway Tint, Lei Sun, Melvin Khee Shing Leow
Thyroid hormones (TH), adiponectin and brown adipose tissue (BAT) are regulators of energy homoeostasis. Influence of BAT activity on the relationship between TH and adiponectin remains unexplored. The aim of the study was to identify the relationship between TH and adiponectin and to clarify the impact of active BAT on the metabolic effects of adiponectin before and after the correction of thyrotoxicosis. Twenty-one patients with newly diagnosed hyperthyroidism from Graves' disease were recruited. A titration dosing regimen of thionamide anti-thyroid drug (ATD) was used to establish euthyroidism over 12-24 weeks. Anthropometric, biochemical and adipocytokine parameters were measured before and after control of hyperthyroidism. BAT activity was quantified by fusion 18 F-fluorodeoxyglucose (18 F-FDG) PET/MR imaging, and patients were grouped based on BAT status. Plasma adiponectin level was significantly increased following correction of hyperthyroidism in the overall sample. Free thyroxine (FT4) was also identified as a predictor of adiponectin level in thyroid dysfunction. However, significant changes in adiponectin level and correlations involving adiponectin were absent in BAT-positive patients but maintained in BAT-negative patients. BAT activity diminishes the correlative relationship with body composition and abolishes TH and adiponectin relationships when transitioning from a hyperthyroid to euthyroid state.
{"title":"Brown adipose tissue influences adiponectin and thyroid hormone changes during Graves' disease therapy.","authors":"Wei-En Ho, Lijuan Sun, Hui Jen Goh, Mya Thway Tint, Lei Sun, Melvin Khee Shing Leow","doi":"10.1080/21623945.2022.2104509","DOIUrl":"https://doi.org/10.1080/21623945.2022.2104509","url":null,"abstract":"<p><p>Thyroid hormones (TH), adiponectin and brown adipose tissue (BAT) are regulators of energy homoeostasis. Influence of BAT activity on the relationship between TH and adiponectin remains unexplored. The aim of the study was to identify the relationship between TH and adiponectin and to clarify the impact of active BAT on the metabolic effects of adiponectin before and after the correction of thyrotoxicosis. Twenty-one patients with newly diagnosed hyperthyroidism from Graves' disease were recruited. A titration dosing regimen of thionamide anti-thyroid drug (ATD) was used to establish euthyroidism over 12-24 weeks. Anthropometric, biochemical and adipocytokine parameters were measured before and after control of hyperthyroidism. BAT activity was quantified by fusion 18 F-fluorodeoxyglucose (18 F-FDG) PET/MR imaging, and patients were grouped based on BAT status. Plasma adiponectin level was significantly increased following correction of hyperthyroidism in the overall sample. Free thyroxine (FT4) was also identified as a predictor of adiponectin level in thyroid dysfunction. However, significant changes in adiponectin level and correlations involving adiponectin were absent in BAT-positive patients but maintained in BAT-negative patients. BAT activity diminishes the correlative relationship with body composition and abolishes TH and adiponectin relationships when transitioning from a hyperthyroid to euthyroid state.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40565755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/21623945.2021.2014179
Karin Säljö, Peter Apelgren, Linnea Stridh Orrhult, Susann Li, Matteo Amoroso, Paul Gatenholm, Lars Kölby
Three-dimensional (3D)-bioprinted lipoaspirate-derived adipose tissue (LAT) is a potential alternative to lipo-injection for correcting soft-tissue defects. This study investigated the long-term in vivo survival of 3D-bioprinted LAT and its proteomic signature and cellular composition. We performed proteomic and multicolour flow cytometric analyses on the lipoaspirate and 3D-bioprinted LAT constructs were transplanted into nude mice, followed by explantation after up to 150 days. LAT contained adipose-tissue-derived stem cells (ASCs), pericytes, endothelial progenitor cells (EPCs) and endothelial cells. Proteomic analysis identified 6,067 proteins, including pericyte markers, adipokines, ASC secretome proteins, proangiogenic proteins and proteins involved in adipocyte differentiation and developmental morphogenic signalling, as well as proteins not previously described in human subcutaneous fat. 3D-bioprinted LAT survived for 150 days in vivo with preservation of the construct shape and size. Furthermore, we identified human blood vessels after 30 and 150 days in vivo, indicating angiogenesis from capillaries. These results showed that LAT has a favourable proteomic signature, contains ASCs, EPCs and blood vessels that survive 3D bioprinting and can potentially facilitate angiogenesis and successful autologous fat grafting in soft-tissue reconstruction.
三维(3D)生物打印的阿司匹林衍生脂肪组织(LAT)是一种潜在的脂肪注射替代方法,可用于矫正软组织缺损。本研究调查了三维生物打印脂肪组织的长期体内存活情况及其蛋白质组特征和细胞组成。我们对吸出的脂肪进行了蛋白质组学和多色流式细胞分析,并将三维生物打印 LAT 构建物移植到裸鼠体内,最长 150 天后再进行移植。LAT包含脂肪组织衍生干细胞(ASCs)、周细胞、内皮祖细胞(EPCs)和内皮细胞。蛋白质组分析确定了6067种蛋白质,包括周细胞标志物、脂肪因子、ASC分泌组蛋白、促血管生成蛋白、参与脂肪细胞分化和发育形态发生信号的蛋白,以及以前未在人类皮下脂肪中描述过的蛋白。三维生物打印的 LAT 在体内存活了 150 天,并保持了构建体的形状和大小。此外,我们还发现了在体内存活 30 天和 150 天的人体血管,这表明血管是由毛细血管生成的。这些结果表明,LAT 具有有利的蛋白质组特征,含有能在三维生物打印中存活的 ASCs、EPCs 和血管,有可能促进血管生成,并在软组织重建中成功进行自体脂肪移植。
{"title":"Long-term <i>in vivo</i> survival of 3D-bioprinted human lipoaspirate-derived adipose tissue: proteomic signature and cellular content.","authors":"Karin Säljö, Peter Apelgren, Linnea Stridh Orrhult, Susann Li, Matteo Amoroso, Paul Gatenholm, Lars Kölby","doi":"10.1080/21623945.2021.2014179","DOIUrl":"10.1080/21623945.2021.2014179","url":null,"abstract":"<p><p>Three-dimensional (3D)-bioprinted lipoaspirate-derived adipose tissue (LAT) is a potential alternative to lipo-injection for correcting soft-tissue defects. This study investigated the long-term <i>in vivo</i> survival of 3D-bioprinted LAT and its proteomic signature and cellular composition. We performed proteomic and multicolour flow cytometric analyses on the lipoaspirate and 3D-bioprinted LAT constructs were transplanted into nude mice, followed by explantation after up to 150 days. LAT contained adipose-tissue-derived stem cells (ASCs), pericytes, endothelial progenitor cells (EPCs) and endothelial cells. Proteomic analysis identified 6,067 proteins, including pericyte markers, adipokines, ASC secretome proteins, proangiogenic proteins and proteins involved in adipocyte differentiation and developmental morphogenic signalling, as well as proteins not previously described in human subcutaneous fat. 3D-bioprinted LAT survived for 150 days <i>in vivo</i> with preservation of the construct shape and size. Furthermore, we identified human blood vessels after 30 and 150 days <i>in vivo</i>, indicating angiogenesis from capillaries. These results showed that LAT has a favourable proteomic signature, contains ASCs, EPCs and blood vessels that survive 3D bioprinting and can potentially facilitate angiogenesis and successful autologous fat grafting in soft-tissue reconstruction.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.5,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8726626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39766954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/21623945.2022.2089394
Helen Imrie, Hema Viswambharan, Natalie J Haywood, Katherine I Bridge, Nadira Y Yuldasheva, Stacey Galloway, Katie J Simmons, Richard M Cubbon, Piruthivi Sukumar, Nicole T Watt, Laeticia Lichtenstein, Judy I Wyatt, Hiromi Kudo, Robert Goldin, Baptiste Rode, Stephen B Wheatcroft, Mark T Kearney
High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD. Mice treated with cixutumumab fed standard chow developed mild hyperinsulinemia with no change in WAT. When challenged by HFD mice treated with cixutumumab had reduced weight gain, reduced WAT expansion, and reduced hepatic lipid vacuole formation. In HFD-fed mice, cixutumumab led to reduced levels of genes encoding proteins important in fatty acid metabolism in WAT and liver. Cixutumumab protected against blunting of insulin-stimulated phosphorylation of Akt in liver of HFD fed mice. These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance.
{"title":"Cixutumumab reveals a critical role for IGF-1 in adipose and hepatic tissue remodelling during the development of diet-induced obesity.","authors":"Helen Imrie, Hema Viswambharan, Natalie J Haywood, Katherine I Bridge, Nadira Y Yuldasheva, Stacey Galloway, Katie J Simmons, Richard M Cubbon, Piruthivi Sukumar, Nicole T Watt, Laeticia Lichtenstein, Judy I Wyatt, Hiromi Kudo, Robert Goldin, Baptiste Rode, Stephen B Wheatcroft, Mark T Kearney","doi":"10.1080/21623945.2022.2089394","DOIUrl":"https://doi.org/10.1080/21623945.2022.2089394","url":null,"abstract":"<p><p>High fat diet (HFD)-induced obesity leads to perturbation in the storage function of white adipose tissue (WAT) resulting in deposition of lipids in tissues ill-equipped to deal with this challenge. The role of insulin like growth factor-1 (IGF-1) in the systemic and organ-specific responses to HFD is unclear. Using cixutumumab, a monoclonal antibody that internalizes and degrades cell surface IGF-1 receptors (IGF-1 R), leaving insulin receptor expression unchanged we aimed to establish the role of IGF-1 R in the response to a HFD. Mice treated with cixutumumab fed standard chow developed mild hyperinsulinemia with no change in WAT. When challenged by HFD mice treated with cixutumumab had reduced weight gain, reduced WAT expansion, and reduced hepatic lipid vacuole formation. In HFD-fed mice, cixutumumab led to reduced levels of genes encoding proteins important in fatty acid metabolism in WAT and liver. Cixutumumab protected against blunting of insulin-stimulated phosphorylation of Akt in liver of HFD fed mice. These data reveal an important role for IGF-1 R in the WAT and hepatic response to short-term nutrient excess. IGF-1 R inhibition during HFD leads to a lipodystrophic phenotype with a failure of WAT lipid storage and protection from HFD-induced hepatic insulin resistance.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9235901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9114661","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/21623945.2022.2129060
Florian M Hatzmann, Sonja Großmann, Petra Waldegger, G Jan Wiegers, Markus Mandl, Tina Rauchenwald, Gerhard Pierer, Werner Zwerschke
The capacity of adipose stem/progenitor cells (ASCs) to undergo self-renewal and differentiation is crucial for adipose tissue homoeostasis, regeneration and expansion. However, the heterogeneous ASC populations of the adipose lineage constituting adipose tissue are not precisely known. In the present study, we demonstrate that cell surface expression of dipeptidyl peptidase-4 (DPP4)/cluster of differentiation 26 (CD26) subdivides the DLK1-/CD34+/CD45-/CD31- ASC pool of human white adipose tissues (WATs) into two large populations. Ex vivo, DPP4+ ASCs possess higher self-renewal and proliferation capacity and lesser adipocyte differentiation potential than DDP4- ASCs. The knock-down of DPP4 in ASC leads to significantly reduced proliferation and self-renewal capacity, while adipogenic differentiation is increased. Ectopic overexpression of DPP4 strongly inhibits adipogenesis. Moreover, in whole mount stainings of human subcutaneous (s)WAT, we detect DPP4 in CD34+ ASC located in the vascular stroma surrounding small blood vessels and in mature adipocytes. We conclude that DPP4 is a functional marker for an abundant ASC population in human WAT with high proliferation and self-renewal potential and low adipogenic differentiation capacity.
{"title":"Dipeptidyl peptidase-4 cell surface expression marks an abundant adipose stem/progenitor cell population with high stemness in human white adipose tissue.","authors":"Florian M Hatzmann, Sonja Großmann, Petra Waldegger, G Jan Wiegers, Markus Mandl, Tina Rauchenwald, Gerhard Pierer, Werner Zwerschke","doi":"10.1080/21623945.2022.2129060","DOIUrl":"https://doi.org/10.1080/21623945.2022.2129060","url":null,"abstract":"<p><p>The capacity of adipose stem/progenitor cells (ASCs) to undergo self-renewal and differentiation is crucial for adipose tissue homoeostasis, regeneration and expansion. However, the heterogeneous ASC populations of the adipose lineage constituting adipose tissue are not precisely known. In the present study, we demonstrate that cell surface expression of dipeptidyl peptidase-4 (DPP4)/cluster of differentiation 26 (CD26) subdivides the DLK1<sup>-</sup>/CD34<sup>+</sup>/CD45<sup>-</sup>/CD31<sup>-</sup> ASC pool of human white adipose tissues (WATs) into two large populations. <i>Ex vivo</i>, DPP4<sup>+</sup> ASCs possess higher self-renewal and proliferation capacity and lesser adipocyte differentiation potential than DDP4<sup>-</sup> ASCs. The knock-down of DPP4 in ASC leads to significantly reduced proliferation and self-renewal capacity, while adipogenic differentiation is increased. Ectopic overexpression of DPP4 strongly inhibits adipogenesis. Moreover, in whole mount stainings of human subcutaneous (s)WAT, we detect DPP4 in CD34<sup>+</sup> ASC located in the vascular stroma surrounding small blood vessels and in mature adipocytes. We conclude that DPP4 is a functional marker for an abundant ASC population in human WAT with high proliferation and self-renewal potential and low adipogenic differentiation capacity.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9542856/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9180569","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Increasing studies have identified the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in non-alcoholic fatty liver disease (NAFLD) treatment. Hence, we further focused on the potential of adipose-derived MSC (ADSC)-EVs in NAFLD by delivering miR-223-3p. The uptake of isolated ADSC-EVs by hepatocytes was assessed, and the expression of miR-223-3p in ADSC-EVs and hepatocytes was characterized. It was established that miR-223-3p, enriched in ADSC-EVs, could be delivered by ADSC-EVs into hepatocytes. Using co-culture system and gain-of-function approach, we evaluated the effect of ADSC-EVs carrying miR-223-3p on lipid accumulation and liver fibrosis in pyrrolizidine alkaloids (PA)-induced hepatocytes and a high-fat diet-induced NAFLD mouse model. Bioinformatics websites and dual-luciferase reporter gene assay were performed to determine the interactions between miR-223-3p and E2F1, which was further validated by rescue experiments. ADSC-EVs containing miR-223-3p displayed suppressive effects on lipid accumulation and liver fibrosis through E2F1 inhibition, since E2F1 was demonstrated as a target gene of miR-223-3p. The protective role of ADSC-EVs by delivering miR-223-3p was then confirmed in the mouse model. Collectively, this study elucidated that ADSC-EVs delayed the progression NAFLD through the delivery of anti-fibrotic miR-223-3p and subsequent E2F1 suppression, which may suggest miR-223-3p-loaded ADSC-EVs to be a potential therapeutic approach for NAFLD.
{"title":"Adipose-derived mesenchymal stem cell-secreted extracellular vesicles alleviate non-alcoholic fatty liver disease <i>via</i> delivering miR-223-3p.","authors":"Qinghui Niu, Ting Wang, Zhiqiang Wang, Feng Wang, Deyu Huang, Huali Sun, Hanyun Liu","doi":"10.1080/21623945.2022.2098583","DOIUrl":"https://doi.org/10.1080/21623945.2022.2098583","url":null,"abstract":"<p><p>Increasing studies have identified the potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) in non-alcoholic fatty liver disease (NAFLD) treatment. Hence, we further focused on the potential of adipose-derived MSC (ADSC)-EVs in NAFLD by delivering miR-223-3p. The uptake of isolated ADSC-EVs by hepatocytes was assessed, and the expression of miR-223-3p in ADSC-EVs and hepatocytes was characterized. It was established that miR-223-3p, enriched in ADSC-EVs, could be delivered by ADSC-EVs into hepatocytes. Using co-culture system and gain-of-function approach, we evaluated the effect of ADSC-EVs carrying miR-223-3p on lipid accumulation and liver fibrosis in pyrrolizidine alkaloids (PA)-induced hepatocytes and a high-fat diet-induced NAFLD mouse model. Bioinformatics websites and dual-luciferase reporter gene assay were performed to determine the interactions between miR-223-3p and E2F1, which was further validated by rescue experiments. ADSC-EVs containing miR-223-3p displayed suppressive effects on lipid accumulation and liver fibrosis through E2F1 inhibition, since E2F1 was demonstrated as a target gene of miR-223-3p. The protective role of ADSC-EVs by delivering miR-223-3p was then confirmed in the mouse model. Collectively, this study elucidated that ADSC-EVs delayed the progression NAFLD through the delivery of anti-fibrotic miR-223-3p and subsequent E2F1 suppression, which may suggest miR-223-3p-loaded ADSC-EVs to be a potential therapeutic approach for NAFLD.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9481107/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10626499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A rapid increase has been observed in insulin resistance (IR) incidence induced by a long-term olanzapine treatment with no better ways to avoid it. Our study aimed to demonstrate the mechanism underlying the olanzapine-induced insulin resistance and find appropriate drug interventions. In this study, firstly, we constructed rat insulin resistance model using a two-month gavage of olanzapine and used the main active ingredient mixture of Gegen Qinlian Decoction for the treatment. The activity of brown adipose tissue (BAT) was measured using the PET/CT scan, whereas Western blot and quantitative real-time PCR were used to detect the expression of GLUT4 and UCP1. The results showed that the long-term administration of olanzapine impaired glucose tolerance and produced insulin resistance in rats, while Gegen Qinlian Decoction could improve this side effect. The results of the PET/CT scan showed that the BAT activity in the insulin-resistant rats was significantly lower than that of the Gegen Qinlian Decoction treated rats. Also, the expression of GLUT4 and UCP1 in the insulin resistance group showed a significant decrease, which could be up-regulated by Gegen Qinliane Decoction treatment. The results of both in vivo and in vitro experiments were consistent. we demonstrated that the olanzapine could induce IR in vitro and in vivo by decreasing the expression of UCP1; thus, suppressing the thermogenesis of BAT and impairing glucose uptake. More importantly, we demonstrated a possible novel strategy to improve the olanzapine-induced IR by Gegen Qinlian Decoction.
{"title":"The mechanisms underlying olanzapine-induced insulin resistance via the brown adipose tissue and the therapy in rats.","authors":"Jing Wang, Qian Wu, Yuan Zhou, Liangyu Yu, Lixiu Yu, Yahui Deng, Chuyue Tu, Weiyong Li","doi":"10.1080/21623945.2022.2026590","DOIUrl":"https://doi.org/10.1080/21623945.2022.2026590","url":null,"abstract":"<p><p>A rapid increase has been observed in insulin resistance (IR) incidence induced by a long-term olanzapine treatment with no better ways to avoid it. Our study aimed to demonstrate the mechanism underlying the olanzapine-induced insulin resistance and find appropriate drug interventions. In this study, firstly, we constructed rat insulin resistance model using a two-month gavage of olanzapine and used the main active ingredient mixture of Gegen Qinlian Decoction for the treatment. The activity of brown adipose tissue (BAT) was measured using the PET/CT scan, whereas Western blot and quantitative real-time PCR were used to detect the expression of GLUT4 and UCP1. The results showed that the long-term administration of olanzapine impaired glucose tolerance and produced insulin resistance in rats, while Gegen Qinlian Decoction could improve this side effect. The results of the PET/CT scan showed that the BAT activity in the insulin-resistant rats was significantly lower than that of the Gegen Qinlian Decoction treated rats. Also, the expression of GLUT4 and UCP1 in the insulin resistance group showed a significant decrease, which could be up-regulated by Gegen Qinliane Decoction treatment. The results of both in vivo and in vitro experiments were consistent. we demonstrated that the olanzapine could induce IR in vitro and in vivo by decreasing the expression of UCP1; thus, suppressing the thermogenesis of BAT and impairing glucose uptake. More importantly, we demonstrated a possible novel strategy to improve the olanzapine-induced IR by Gegen Qinlian Decoction.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8786323/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39850842","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Strong links have been reported among trimethylamine N-oxide (TMAO), visceral white adipose tissue (vWAT), and cardiometabolic diseases. However, the effects of TMAO on vWAT in hypertension remained incompletely explored. The impact of a chronic 22-week-long treatment with 1 g/L TMAO on vWAT, and its transcriptional and metabolic changes in spontaneously hypertensive rats (SHRs) were evaluated by serum cytokine measurements, histological analysis, fatty acid determinations, and co-expression network analyses. TMAO increased the serum interleukin-6 levels and insulin secretion in SHRs. The adipocyte size was diminished in the SHR 1 g/L TMAO group. In addition, one kind of monounsaturated fatty acids (cis-15-tetracosenoate) and four kinds of polyunsaturated fatty acids (cis-11,14,17-eicosatrienoic acid, docosatetraenoate, docosapentaenoate n-3, and docosapentaenoate n-6) were elevated by TMAO treatment. Three co-expression modules significantly related to TMAO treatment were identified and pathway enrichment analyses indicated that phagosome, lysosome, fatty acid metabolism, valine, leucine, and isoleucine degradation and metabolic pathways were the most significantly altered biological pathways. This study shed new light on the metabolic roles of TMAO on the vWAT of SHRs. TMAO regulated the metabolic status of vWAT, including reduced lipogenesis and an improved specific fatty acid composition. The mechanisms underlying these effects likely involve phagosome and lysosome pathways.
{"title":"The effect of trimethylamine N-oxide on the metabolism of visceral white adipose tissue in spontaneously hypertensive rat.","authors":"Guo-Dong He, Xiao-Cong Liu, Xing-Hua Hou, Ying-Qing Feng","doi":"10.1080/21623945.2022.2104783","DOIUrl":"https://doi.org/10.1080/21623945.2022.2104783","url":null,"abstract":"<p><p>Strong links have been reported among trimethylamine N-oxide (TMAO), visceral white adipose tissue (vWAT), and cardiometabolic diseases. However, the effects of TMAO on vWAT in hypertension remained incompletely explored. The impact of a chronic 22-week-long treatment with 1 g/L TMAO on vWAT, and its transcriptional and metabolic changes in spontaneously hypertensive rats (SHRs) were evaluated by serum cytokine measurements, histological analysis, fatty acid determinations, and co-expression network analyses. TMAO increased the serum interleukin-6 levels and insulin secretion in SHRs. The adipocyte size was diminished in the SHR 1 g/L TMAO group. In addition, one kind of monounsaturated fatty acids (cis-15-tetracosenoate) and four kinds of polyunsaturated fatty acids (cis-11,14,17-eicosatrienoic acid, docosatetraenoate, docosapentaenoate n-3, and docosapentaenoate n-6) were elevated by TMAO treatment. Three co-expression modules significantly related to TMAO treatment were identified and pathway enrichment analyses indicated that phagosome, lysosome, fatty acid metabolism, valine, leucine, and isoleucine degradation and metabolic pathways were the most significantly altered biological pathways. This study shed new light on the metabolic roles of TMAO on the vWAT of SHRs. TMAO regulated the metabolic status of vWAT, including reduced lipogenesis and an improved specific fatty acid composition. The mechanisms underlying these effects likely involve phagosome and lysosome pathways.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387326/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633594","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/21623945.2022.2107195
Ziwei Cui, Qian Tan
In cell-assisted lipotransfer, adipose-derived stem cells play a crucial role in enhancing fat graft retention. In vitro, human adipose-derived stem cells were modified with Bcl-2 gene. In vivo, aspirated fat was mixed with the Bcl-2-modified adipose-derived stem cells and then transplanted subcutaneously into nude mice. The retention of fat graft was evaluated. The surviving Bcl-2-modified adipose-derived stem cells were tracked after transplantation. Capillary density was quantified after transplantation. Transplantation with Bcl-2-modified adipose-derived stem cells enhanced fat graft retention by 49% and 114% at 6 weeks compared with the Fat + vector-modified adipose-derived stem cell group and Fat-only group, respectively. Transplants from the Fat + Bcl-2-modified adipose-derived stem cell group had significantly more intact adipocytes and lower levels of fat necrosis and fibrosis at 6 weeks. The survival of Bcl-2-modified adipose-derived stem cells increased by 33% at 3 weeks and 54% at 6 weeks, respectively, compared with vector-modified adipose-derived stem cells. The capillary density was 24% higher in Fat + Bcl-2-modified adipose-derived stem cell group than in Fat + vector-modified adipose-derived stem cell group or 60% higher than in Fat-only group at 3 weeks.
{"title":"Bcl-2 modified adipose-derived stem cells improve the retention of fat graft.","authors":"Ziwei Cui, Qian Tan","doi":"10.1080/21623945.2022.2107195","DOIUrl":"https://doi.org/10.1080/21623945.2022.2107195","url":null,"abstract":"<p><p>In cell-assisted lipotransfer, adipose-derived stem cells play a crucial role in enhancing fat graft retention. <i>In vitro</i>, human adipose-derived stem cells were modified with Bcl-2 gene. In vivo, aspirated fat was mixed with the Bcl-2-modified adipose-derived stem cells and then transplanted subcutaneously into nude mice. The retention of fat graft was evaluated. The surviving Bcl-2-modified adipose-derived stem cells were tracked after transplantation. Capillary density was quantified after transplantation. Transplantation with Bcl-2-modified adipose-derived stem cells enhanced fat graft retention by 49% and 114% at 6 weeks compared with the Fat + vector-modified adipose-derived stem cell group and Fat-only group, respectively. Transplants from the Fat + Bcl-2-modified adipose-derived stem cell group had significantly more intact adipocytes and lower levels of fat necrosis and fibrosis at 6 weeks. The survival of Bcl-2-modified adipose-derived stem cells increased by 33% at 3 weeks and 54% at 6 weeks, respectively, compared with vector-modified adipose-derived stem cells. The capillary density was 24% higher in Fat + Bcl-2-modified adipose-derived stem cell group than in Fat + vector-modified adipose-derived stem cell group or 60% higher than in Fat-only group at 3 weeks.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9387309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40633595","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-12-01DOI: 10.1080/21623945.2022.2111053
Lei Li, Qian Wan, Qiaoyun Long, Tao Nie, Shiting Zhao, Liufeng Mao, Chuanli Cheng, Chao Zou, Kerry Loomes, Aimin Xu, Liangxue Lai, Xin Liu, Ziyuan Duan, Xiaoyan Hui, Donghai Wu
Interscapular brown adipose tissue (iBAT) of both rabbits and humans exhibits a similar whitening phenomenon under physiological conditions. However, a detailed characterization of iBAT whitening in them is still lacking. Here, we chose rabbits as a model to gain a better understanding of the molecular signature changes during the whitening process of iBAT by transcriptomic analysis of rabbit iBAT at day 1, day 14, 1 month and 4 months after birth. We applied non-invasive MRI imaging to monitor the whitening process and correlated these changes with analysis of morphological, histological and molecular features. Principal component analysis (PCA) of differentially expressed genes delineated three major phases for the whitening process as Brown, Transition and Whitened BAT phases. RNA-sequencing data revealed that whitening of iBAT was an orchestrated process where multiple types of cells and tissues participated in a variety of physiological processes including neovascularization, formation of new nervous networks and immune regulation. Several key metabolic and signalling pathways contributed to whitening of iBAT, and immune cells and immune regulation appeared to play an overarching role.
{"title":"Comparative transcriptomic analysis of rabbit interscapular brown adipose tissue whitening under physiological conditions.","authors":"Lei Li, Qian Wan, Qiaoyun Long, Tao Nie, Shiting Zhao, Liufeng Mao, Chuanli Cheng, Chao Zou, Kerry Loomes, Aimin Xu, Liangxue Lai, Xin Liu, Ziyuan Duan, Xiaoyan Hui, Donghai Wu","doi":"10.1080/21623945.2022.2111053","DOIUrl":"https://doi.org/10.1080/21623945.2022.2111053","url":null,"abstract":"<p><p>Interscapular brown adipose tissue (iBAT) of both rabbits and humans exhibits a similar whitening phenomenon under physiological conditions. However, a detailed characterization of iBAT whitening in them is still lacking. Here, we chose rabbits as a model to gain a better understanding of the molecular signature changes during the whitening process of iBAT by transcriptomic analysis of rabbit iBAT at day 1, day 14, 1 month and 4 months after birth. We applied non-invasive MRI imaging to monitor the whitening process and correlated these changes with analysis of morphological, histological and molecular features. Principal component analysis (PCA) of differentially expressed genes delineated three major phases for the whitening process as Brown, Transition and Whitened BAT phases. RNA-sequencing data revealed that whitening of iBAT was an orchestrated process where multiple types of cells and tissues participated in a variety of physiological processes including neovascularization, formation of new nervous networks and immune regulation. Several key metabolic and signalling pathways contributed to whitening of iBAT, and immune cells and immune regulation appeared to play an overarching role.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":null,"pages":null},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9427046/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10625211","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}