AdipocytePub Date : 2023-12-01Epub Date: 2023-10-13DOI: 10.1080/21623945.2023.2264444
Chen Lei, Jing Wang, Xin Li, Yuan-Yuan Mao, Jian-Qun Yan
{"title":"Changes of insulin receptors in high fat and high glucose diet mice with insulin resistance.","authors":"Chen Lei, Jing Wang, Xin Li, Yuan-Yuan Mao, Jian-Qun Yan","doi":"10.1080/21623945.2023.2264444","DOIUrl":"10.1080/21623945.2023.2264444","url":null,"abstract":"<p><p>This study aimed to observe the expression of insulin-signaling molecules in different organs of mice with insulin resistance (IR). Firstly, mice were fed a high-fat and high-sugar diet (HF group) to establish an IR model, and the controls (NF group) were fed with a normal diet. Next, the weight, fasting blood glucose (FBG), serum insulin and insulin tolerance were detected. Pathological changes of liver tissues were observed by H&E staining. The expressions of INSR, IRS-1 and IRS-2 in the liver, skeletal muscle and ovary were measured by qRT-PCR and western blotting. As a result, compared with the NF group, the HF group mice had increased weight, FBG, insulin and IR index after 6-week of feeding as well as a worse performance in the insulin tolerance test and H&E staining showed fatty liver-like changes after 12-week of feeding, exhibited lower expression of INSR, IRS-1 and IRS-2 in the liver of mice at 6 and 12 weeks. The expression of INSR and IRS-1 in skeletal muscle tissues exhibited the same trend, while those in ovary organs showed the opposite trend. These results suggested that the insulin signaling alters in the liver, skeletal muscle and ovary organs with the progress of IR.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"12 1","pages":"2264444"},"PeriodicalIF":3.3,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10578188/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41187962","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}
AdipocytePub Date : 2023-12-01DOI: 10.1080/21623945.2023.2194034
Ryan Ting, Heidi Dutton, Alexander Sorisky
{"title":"<i>In vitro</i> studies of the renin-angiotensin system in human adipose tissue/adipocytes and possible relationship to SARS-CoV-2: a scoping review.","authors":"Ryan Ting, Heidi Dutton, Alexander Sorisky","doi":"10.1080/21623945.2023.2194034","DOIUrl":"10.1080/21623945.2023.2194034","url":null,"abstract":"<p><p>The renin-angiotensin system (RAS) operates within adipose tissue. Obesity-related changes can affect adipose RAS, predisposing to hypertension, type 2 diabetes, and possibly severe COVID-19. We evaluated the <i>in vitro</i> research on human adipose RAS and identified gaps in the literature. Medline (Ovid), Embase (Ovid), Web of Science, Scopus, and 1findr were searched to identify relevant studies. Fifty primary studies met our inclusion criteria for analysis. Expression of RAS components (<i>n</i> = 14), role in differentiation (<i>n</i> = 14), association with inflammation (<i>n</i> = 15) or blood pressure (<i>n</i> = 7) were investigated. We found (1) obesity-related changes in RAS were frequently studied (30%); (2) an upswing of articles investigating adipose ACE-2 expression since the COVID-19 pandemic; (3) a paucity of papers on AT2R and Ang (1-7)/MasR which counterbalance Ang II/ART1; (4) weight loss lowered adipose ACE-2 mRNA expression; and (5) angiotensin receptor blockers (ARBs) reduced deleterious effects of angiotensin II. Overall, these studies link Ang II/ATR1 signalling to impaired adipogenesis and a pro-inflammatory dysfunctional adipose tissue, with ATR1 blockade limiting these responses. ACE-2 may mitigate Ang II effects by converting it to Ang(1-7) which binds MasR. More work is needed to understand adipose RAS in various pathologic states such as obesity and COVID-19 infection.T.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":"12 1","pages":"2194034"},"PeriodicalIF":3.5,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054178/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9286679","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}
AdipocytePub Date : 2022-12-01DOI: 10.1080/21623945.2021.2013416
Alexander W Fischer, Michelle Y Jaeckstein, Joerg Heeren
{"title":"Lysosomal acid lipase promotes endothelial proliferation in cold-activated adipose tissue.","authors":"Alexander W Fischer, Michelle Y Jaeckstein, Joerg Heeren","doi":"10.1080/21623945.2021.2013416","DOIUrl":"https://doi.org/10.1080/21623945.2021.2013416","url":null,"abstract":"<p><p>Oxidative tissues such as brown adipose tissue and muscle internalize large amounts of circulating lipids and glucose as energy source. Endothelial cells (ECs) provide a platform for regulated transport and processing of blood-borne nutrients. Next to this role, it has become recognized that intercellular crosstalk between ECs and underlying parenchymal cells is indispensable for maintenance of tissue homoeostasis. Here, we comment on our recent observation that capillary ECs in thermogenic adipose tissues take up and metabolize entire triglyceride-rich lipoprotein (TRL) particles in response to cold exposure. This process is dependent on CD36, lipoprotein lipase (LPL) and lysosomal acid lipase (LAL). Remarkably, loss of LAL specifically in endothelial cells results in impaired endothelial proliferation and diminished thermogenic adaptation. Mechanistically, cell culture experiments indicate that LAL-mediated TRL processing leads to the generation of reactive oxygen species, which in turn activate hypoxia-induced factor (HIF)-mediated proliferative responses. In the current manuscript, we provide <i>in vivo</i> evidence that LAL-deficiency impairs proliferation of endothelial cells in thermogenic adipose tissue. In addition, we show uptake of nanoparticle-labelled TRL and LAL expression in cardiac endothelial cells, suggesting a physiological function of endothelial lipoprotein processing not only in thermogenic adipose tissue but also in cardiac muscle.</p>","PeriodicalId":7226,"journal":{"name":"Adipocyte","volume":" ","pages":"28-33"},"PeriodicalIF":3.3,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8726628/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"39764606","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}
AdipocytePub 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
{"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":" ","pages":"389-400"},"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}
{"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":" ","pages":"84-98"},"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}
{"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":"11 1","pages":"572-587"},"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}
AdipocytePub 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
{"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":"11 1","pages":"601-615"},"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}
{"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":" ","pages":"420-433"},"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}
AdipocytePub Date : 2022-12-01DOI: 10.1080/21623945.2022.2107195
Ziwei Cui, Qian Tan
{"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":" ","pages":"501-509"},"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}
AdipocytePub 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
{"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":"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":"11 1","pages":"366-378"},"PeriodicalIF":3.5,"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}