Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 32.399
Filtrar
1.
Front Endocrinol (Lausanne) ; 13: 955593, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120427

RESUMO

Pioglitazone, a PPARγ agonist, is used to treat type 2 diabetes (T2D). PPARγ is highly expressed in adipose tissue (AT), however the effects of pioglitazone to improve insulin sensitivity are also evident in other tissues and PPARγ agonism has been shown to alter cancer derived extracellular vesicle (EV)-miRNAs. We hypothesized that pioglitazone modifies the cargo of circulating AT-derived EVs to alter interorgan crosstalk in people with diabetes. We tested our hypothesis in a 3-month trial in which 24 subjects with T2D were randomized to treatment with either pioglitazone 45 mg/day or placebo (NCT00656864). Levels of 42 adipocyte-derived EV-miRNAs were measured in plasma EVs using low density TaqMan arrays. Levels of differentially expressed EV-miRNAs and their most relevant target genes were also measure in adipose tissue from the same participants, using individual TaqMan assays. Levels of 5 miRNAs (i.e., miR-7-5p, miR-20a-5p, miR-92a-3p, miR-195-5p, and miR-374b-5p) were significantly downregulated in EVs in response to pioglitazone treatment relative to placebo. The opposite occurred for miR-195-5p in subcutaneous AT. Changes in miRNA expression in EVs and AT correlated with changes in suppression of lipolysis and improved insulin sensitivity, among others. DICER was downregulated and exosomal miRNA sorting-related genes YBX1 and hnRNPA2B1 displayed a downregulation trend in AT. Furthermore, analysis of EV-miRNA targeted genes identified a network of transcripts that changed in a coordinated manner in AT. Collectively, our results suggest that some beneficial pharmacologic effects of pioglitazone are mediated by adipose-specific miRNA regulation and exosomal/EV trafficking. Clinical Trial Registration: ClinicalTrials.gov, identifier NCT00656864.


Assuntos
Diabetes Mellitus Tipo 2 , Vesículas Extracelulares , Resistência à Insulina , MicroRNAs , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Humanos , MicroRNAs/metabolismo , PPAR gama/genética , PPAR gama/metabolismo , Pioglitazona/metabolismo
2.
Front Endocrinol (Lausanne) ; 13: 995499, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36120469

RESUMO

During hypertension, vascular remodeling allows the blood vessel to withstand mechanical forces induced by high blood pressure (BP). This process is well characterized in the media and intima layers of the vessel but not in the perivascular adipose tissue (PVAT). In PVAT, there is evidence for fibrosis development during hypertension; however, PVAT remodeling is poorly understood. In non-PVAT depots, mechanical forces can affect adipogenesis and lipogenic stages in preadipocytes. In tissues exposed to high magnitudes of pressure like bone, the activation of the mechanosensor PIEZO1 induces differentiation of progenitor cells towards osteogenic lineages. PVAT's anatomical location continuously exposes it to forces generated by blood flow that could affect adipogenesis in normotensive and hypertensive states. In this study, we hypothesize that activation of PIEZO1 reduces adipogenesis in PVAT preadipocytes. The hypothesis was tested using pharmacological and mechanical activation of PIEZO1. Thoracic aorta PVAT (APVAT) was collected from 10-wk old male SD rats (n=15) to harvest preadipocytes that were differentiated to adipocytes in the presence of the PIEZO1 agonist Yoda1 (10 µM). Mechanical stretch was applied with the FlexCell System at 12% elongation, half-sine at 1 Hz simultaneously during the 4 d of adipogenesis (MS+, mechanical force applied; MS-, no mechanical force used). Yoda1 reduced adipogenesis by 33% compared with CON and, as expected, increased cytoplasmic Ca2+ flux. MS+ reduced adipogenesis efficiency compared with MS-. When Piezo1 expression was blocked with siRNA [siPiezo1; NC=non-coding siRNA], the anti-adipogenic effect of Yoda1 was reversed in siPiezo1 cells but not in NC; in contrast, siPiezo1 did not alter the inhibitory effect of MS+ on adipogenesis. These data demonstrate that PIEZO1 activation in PVAT reduces adipogenesis and lipogenesis and provides initial evidence for an adaptive response to excessive mechanical forces in PVAT during hypertension.


Assuntos
Adipogenia , Hipertensão , Tecido Adiposo/metabolismo , Animais , Cálcio/metabolismo , Masculino , Mecanorreceptores/metabolismo , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley
3.
Adipocyte ; 11(1): 588-600, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36082406

RESUMO

Obesity is a chronic metabolic disorder characterized by the accumulation of excess fat in the body. Preventing and controlling obesity by inhibiting the adipogenic differentiation of mesenchymal stem cells (MSCs) and thereby avoiding the increase of white adipose tissue is safe and effective. Recent studies have demonstrated that Sprouty proteins (SPRYs) are involved in cell differentiation and related diseases. However, the role and mechanism of SPRY4 in MSC adipogenic differentiation remain to be explored. Here, we found that SPRY4 positively correlates with the adipogenic differentiation of human adipose-derived MSCs (hAMSCs). Via gain- and loss-of-function experiments, we demonstrated that SPRY4 promotes hAMSC adipogenesis both in vitro and in vivo. Mechanistically, SPRY4 functioned by activating the MEK-ERK1/2 pathway. Our findings provide new insights into a critical role for SPRY4 as a regulator of adipogenic differentiation, which may illuminate the underlying mechanisms of obesity and suggest the potential of SPRY4 as a novel treatment option.


Assuntos
Adipogenia , Células-Tronco Mesenquimais , Tecido Adiposo/metabolismo , Diferenciação Celular , Células Cultivadas , Humanos , Sistema de Sinalização das MAP Quinases , Quinases de Proteína Quinase Ativadas por Mitógeno/metabolismo , Obesidade/metabolismo , Transdução de Sinais
4.
Adv Exp Med Biol ; 1390: 61-82, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36107313

RESUMO

Nuclear receptors are master regulators of energy metabolism through the conversion of extracellular signals into gene expression signatures. The function of the respective nuclear receptor is tissue specific, signal and co-factor dependent. While normal nuclear receptor function is central to metabolic physiology, aberrant nuclear receptor signaling is linked to various metabolic diseases such as type 2 diabetes mellitus, obesity, or hepatic steatosis. Thus, the tissue specific manipulation of nuclear receptors is a major field in biomedical research and represents a treatment approach for metabolic syndrome. This chapter focuses on key nuclear receptors involved in regulating the metabolic function of liver, adipose tissue, skeletal muscle, and pancreatic ß-cells. It also addresses the importance of nuclear co-factors for fine-tuning of nuclear receptor function. The mode of action, role in energy metabolism, and therapeutic potential of prominent nuclear receptors is outlined.


Assuntos
Diabetes Mellitus Tipo 2 , Doenças Metabólicas , Tecido Adiposo/metabolismo , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Metabolismo Energético/fisiologia , Humanos , Doenças Metabólicas/genética , Doenças Metabólicas/metabolismo , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo
5.
Sci Rep ; 12(1): 15437, 2022 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-36104403

RESUMO

The tumor microenvironment represents one of the main obstacles in breast cancer treatment owing to the presence of heterogeneous stromal cells, such as adipose-derived stem cells (ADSCs), that may interact with breast cancer cells and promote cancer development. Resistin is an adipocytokine associated with adverse breast cancer progression; however, its underlying mechanisms in the context of the breast tumor microenvironment remain largely unidentified. Here, we utilized a transwell co-culture model containing patient-derived ADSCs and breast cancer cell lines to investigate their potential interaction, and observed that breast cancer cells co-cultured with resistin-treated ADSCs (R-ADSCs) showed enhanced cancer cell growth and metastatic ability. Screening by proteome arrays revealed that C-X-C motif chemokine ligand 5 (CXCL5) was released in the conditioned medium of the co-culture system, and phosphorylated ERK was increased in breast cancer cells after co-culture with R-ADSCs. Breast cancer cells treated with the recombinant proteins of CXCL5 showed similarly enhanced cell migration and invasion ability as occurred in the co-culture model, whereas application of neutralizing antibodies against CXCL5 reversed these phenomena. The orthotopic xenograft in mice by breast cancer cells after co-culture with R-ADSCs had a larger tumor growth and more CXCL5 expression than control. In addition, clinical analysis revealed a positive correlation between the expression of resistin and CXCL5 in both tumor tissues and serum specimens of breast cancer patients. The current study suggests that resistin-stimulated ADSCs may interact with breast cancer cells in the tumor microenvironment via CXCL5 secretion, leading to breast cancer cell malignancy.


Assuntos
Neoplasias da Mama , Resistina , Tecido Adiposo/metabolismo , Animais , Neoplasias da Mama/patologia , Quimiocina CXCL5/metabolismo , Técnicas de Cocultura , Feminino , Humanos , Camundongos , Resistina/metabolismo , Células-Tronco , Microambiente Tumoral
6.
Animal ; 16(9): 100627, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36084412

RESUMO

Nutrient deficit during the periparturient period leads to mobilisation of body energy and protein reserves. Research regarding fat reserves and mobilisation is extensive, while, on the contrary, investigation of muscle mobilisation during the periparturient period is limited. The aim of this cohort study was to simultaneously investigate the biological variation of skeletal muscle and subcutaneous fat reserves together with their mobilisation in transition Holstein cows of different herds, using ultrasonography, and to assess potential affecting factors. For this purpose, ultrasound measurements of longissimus dorsi muscle thickness (LDT) and backfat thickness (BFT) from 238 multiparous cows of six dairy farms were obtained at six time points across the transition period (from 21 days pre- to 28 days postpartum). Concentrations of serum creatinine and non-esterified fatty acids were determined in order to confirm the loss of muscle mass and adipose tissue, respectively. Cases of clinical postparturient diseases and subclinical ketosis (scKET) during the first 28 days postcalving were recorded. Cows mobilised on average 32.8% and 37.3% of LDT and BFT reserves, respectively. Large between-cow variation was observed for both the onset and the degree of mobilisation. Time point, initial body condition score and parity were the most important predictors of LDT variation. Cows diagnosed with metritis (MET) had lower LDT postpartum and mobilised more muscle depth compared to cows not diagnosed with MET. Initial BCS, time point, initial BW (estimated by heart girth measurement) and parity were the most important predictors of BFT variation. Cows diagnosed with MET mobilised more backfat between -7d and 7d compared to cows not diagnosed with MET. Cows with scKET mobilised more backfat between 7- and 21 days postpartum compared to healthy ones. Variation of subcutaneous fat and skeletal muscle reserves during the transition period was large and affected by herd and several cow-level factors.


Assuntos
Metabolismo Energético , Lactação , Tecido Adiposo/metabolismo , Animais , Bovinos , Estudos de Coortes , Creatinina/metabolismo , Metabolismo Energético/fisiologia , Ácidos Graxos não Esterificados/metabolismo , Feminino , Humanos , Lactação/fisiologia , Leite/metabolismo , Músculo Esquelético/metabolismo , Período Pós-Parto , Gravidez
7.
Front Immunol ; 13: 977485, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119080

RESUMO

Adipose tissue macrophage (ATM) has been appreciated for its critical contribution to obesity-associated metabolic diseases in recent years. Here, we discuss the regulation of ATM on both metabolic homeostatsis and dysfunction. In particular, the macrophage polarization and recruitment as well as the crosstalk between ATM and adipocyte in thermogenesis, obesity, insulin resistance and adipose tissue fibrosis have been reviewed. A better understanding of how ATM regulates adipose tissue remodeling may provide novel therapeutic strategies against obesity and associated metabolic diseases.


Assuntos
Inflamação , Resistência à Insulina , Tecido Adiposo/metabolismo , Humanos , Inflamação/metabolismo , Macrófagos/metabolismo , Obesidade/metabolismo
8.
Stem Cell Res Ther ; 13(1): 463, 2022 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-36068613

RESUMO

BACKGROUND: Urethral stricture and reconstruction are one of the thorny difficult problems in the field of urology. The continuous development of tissue engineering and biomaterials has given new therapeutic thinking to this problem. Bacterial cellulose (BC) is an excellent biomaterial due to its accessibility and strong plasticity. Moreover, adipose-derived stem cells (ADSCs) could enhance their wound healing ability through directional modification. METHODS: First, we used physical drilling and sulfonation in this study to make BC more conducive to cell attachment and degradation. We tested the relevant mechanical properties of these materials. After that, we attached Fibroblast Growth Factor Receptor 2 (FGFR2)-modified ADSCs to the material to construct a urethra for tissue engineering. Afterward, we verified this finding in the male New Zealand rabbit model and carried out immunohistochemical and imaging examinations 1 and 3 months after the operation. At the same time, we detected the potential biological function of FGFR2 by bioinformatics and a cytokine chip. RESULTS: The results show that the composite has excellent repairability and that this ability is correlated with angiogenesis. The new composite in this study provides new insight and therapeutic methods for urethral reconstruction. The preliminary mechanism showed that FGFR2 could promote angiogenesis and tissue repair by promoting the secretion of Vascular Endothelial Growth Factor A (VEGFA) from ADSCs. CONCLUSIONS: Double-modified sulfonated bacterial cellulose scaffolds combined with FGFR2-modified ADSCs provide new sight and treatments for patients with urethral strictures.


Assuntos
Uretra , Fator A de Crescimento do Endotélio Vascular , Tecido Adiposo/metabolismo , Animais , Materiais Biocompatíveis , Celulose , Masculino , Coelhos , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/metabolismo , Células-Tronco/metabolismo , Sulfatos/metabolismo , Engenharia Tecidual/métodos , Tecidos Suporte/química , Fator A de Crescimento do Endotélio Vascular/metabolismo
9.
Anim Sci J ; 93(1): e13769, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36127314

RESUMO

The composition of amino acid and fatty acid has a vital function on meat quality and animal health. However, the underlying mechanism of amino acid and fatty acid metabolism in sheep during different grazing periods is still unclear. In this study, a total of 12 sheep were employed in different grazing periods. Our results showed that the composition of amino acids and fatty acids in muscle and adipose tissues was significantly altered between dry grass (DG) period and green grass (GG) period. Changes in the activities of the metabolism-related enzymes including BCKD, BCAT2, ACC, SCD, HSL, GSK3ß, p-GSK3ß, and FABP4 were observed in muscle and adipose during different grazing periods. In addition, the mRNA expression levels of ACC, FAS, SCD, HSL, LPL, and DGAT1 in muscle and adipose tissue were changed markedly in different grazing periods. Furthermore, the expression levels of mTOR and ß-catenin/PPARγ/C/EBPα pathway-related proteins were predominantly altered in muscle and adipose among DG and GG. Taken together, all investigations simplified the process of amino acid and fatty acid metabolism disorders caused by different grazing periods, and the mTOR and ß-catenin/PPARγ/C/EBPα play the essential role in this process, which provided an underlying mechanism of metabolism and meat quality.


Assuntos
Aminoácidos , Ácidos Graxos , Tecido Adiposo/metabolismo , Aminoácidos/análise , Animais , Ácidos Graxos/análise , Glicogênio Sintase Quinase 3 beta , Músculos/metabolismo , PPAR gama/metabolismo , RNA Mensageiro/metabolismo , Ovinos , Serina-Treonina Quinases TOR/metabolismo , beta Catenina/metabolismo
10.
Nat Commun ; 13(1): 5208, 2022 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-36064857

RESUMO

Adipose tissue macrophage (ATM) inflammation is involved with meta-inflammation and pathology of metabolic complications. Here we report that in adipocytes, elevated lactate production, previously regarded as the waste product of glycolysis, serves as a danger signal to promote ATM polarization to an inflammatory state in the context of obesity. Adipocyte-selective deletion of lactate dehydrogenase A (Ldha), the enzyme converting pyruvate to lactate, protects mice from obesity-associated glucose intolerance and insulin resistance, accompanied by a lower percentage of inflammatory ATM and reduced production of pro-inflammatory cytokines such as interleukin 1ß (IL-1ß). Mechanistically, lactate, at its physiological concentration, fosters the activation of inflammatory macrophages by directly binding to the catalytic domain of prolyl hydroxylase domain-containing 2 (PHD2) in a competitive manner with α-ketoglutarate and stabilizes hypoxia inducible factor (HIF-1α). Lactate-induced IL-1ß was abolished in PHD2-deficient macrophages. Human adipose lactate level is positively linked with local inflammatory features and insulin resistance index independent of the body mass index (BMI). Our study shows a critical function of adipocyte-derived lactate in promoting the pro-inflammatory microenvironment in adipose and identifies PHD2 as a direct sensor of lactate, which functions to connect chronic inflammation and energy metabolism.


Assuntos
Resistência à Insulina , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Animais , Humanos , Inflamação/patologia , Resistência à Insulina/fisiologia , Ácido Láctico/metabolismo , Macrófagos/metabolismo , Camundongos , Obesidade/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Prolil Hidroxilases/metabolismo
11.
Mediators Inflamm ; 2022: 7853482, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36065376

RESUMO

The adipose tissue NLRP3 inflammasome has recently emerged as a contributor to obesity-related metabolic inflammation. Recent studies have demonstrated that the activation of the NLRP3 inflammasome cleaves gasdermin D (GSDMD) and induces pyroptosis, a proinflammatory programmed cell death. However, whether GSDMD is involved in the regulation of adipose tissue function and the development of obesity-induced metabolic disease remains unknown. The aim of the present study was to investigate the role of GSDMD in adipose tissue inflammation as well as whole-body metabolism using GSDMD-deficient mice fed a high-fat diet (HFD) for 30 weeks. The effects of GSDMD deficiency on adipose tissue, liver, and isolated macrophages from wild-type (WT) and GSDMD knockout (KO) mice were examined. In addition, 3T3-L1 cells were used to examine the expression of GSDMD during adipogenesis. The results demonstrate that although HFD-induced inflammation was partly ameliorated in isolated macrophages and liver, adipose tissue remained unaffected by GSDMD deficiency. Compared with the WT HFD mice, GSDMD KO HFD mice exhibited a mild increase in HFD-induced glucose intolerance with increased systemic and adipose tissue IL-1ß levels. Interestingly, GSDMD deficiency caused accumulation of fat mass when challenged with HFD, partly by suppressing the expression of peroxisome proliferator-activated receptor gamma (PPARγ). The expression of GSDMD mRNA and protein was dramatically suppressed during adipocyte differentiation and was inversely correlated with PPARγ expression. Together, these findings indicate that GSDMD is not a prerequisite for HFD-induced adipose tissue inflammation and suggest a noncanonical function of GSDMD in regulation of fat mass through PPARγ.


Assuntos
Tecido Adiposo , Dieta Hiperlipídica , Intolerância à Glucose , Proteínas de Ligação a Fosfato , Proteínas Citotóxicas Formadoras de Poros , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Dieta Hiperlipídica/efeitos adversos , Intolerância à Glucose/metabolismo , Inflamassomos/metabolismo , Inflamação/metabolismo , Camundongos , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Obesidade/metabolismo , PPAR gama/metabolismo , Proteínas de Ligação a Fosfato/genética , Proteínas Citotóxicas Formadoras de Poros/genética
12.
PLoS One ; 17(9): e0273942, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36048868

RESUMO

Obesity is characterized by an adipose tissue mass expansion that presents a risk to health, associated with a chronic increase in circulating inflammatory mediators. Anti-inflammatory agents are an obesity alternative treatment. However, the lack of effective agents indicates the need to assess the mechanisms and identify effective therapeutic targets. The present work identified and described the mechanisms of action of anti-inflammatory agents in adipose tissue in experimental studies. The review was registered in the International Prospective Registry of Systematic Reviews (PROSPERO-CRD42020182897). The articles' selection was according to eligibility criteria (PICOS). The research was performed in PubMed, ScienceDirect, Scopus, Web of Science, VHL, and EMBASE. The methodological quality evaluation was assessed using SYRCLE. Initially, 1511 articles were selected, and at the end of the assessment, 41 were eligible. Among the anti-inflammatory agent classes, eight drugs, 28 natural, and five synthetic compounds were identified. Many of these anti-inflammatory agents act in metabolic pathways that culminate in the inflammatory cytokines expression reduction, decreasing the macrophages infiltration in white and adipose tissue and promoting the polarization process of type M1 to M2 macrophages. Thus, the article clarifies and systematizes these anti-inflammatory agents' mechanisms in adipose tissue, presenting targets relevant to future research on these pathways.


Assuntos
Tecido Adiposo , Inflamação , Tecido Adiposo/metabolismo , Anti-Inflamatórios/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Humanos , Inflamação/metabolismo , Obesidade/complicações , Revisões Sistemáticas como Assunto
13.
Int J Mol Sci ; 23(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36077270

RESUMO

Secreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipocytokine secreted by adipocytes that seems to be linked with nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the role of the SFRP5-wingless-MMTV integration site family member 5a (WNT5A) pathway, closely related to adipogenesis, in subcutaneous (SAT) and visceral adipose tissues (VAT) and its relationship with obesity-related NAFLD. Our cohort was composed of 60 women with morbid obesity (MO), who underwent hypocaloric diet, subclassified according to their hepatic histopathology and 15 women with normal weight. We observed increased SFRP5 mRNA expression in VAT and lower WNT5A expression in SAT in MO compared to normal weight. We found elevated SFRP5 expression in nonalcoholic steatohepatitis (NASH) in SAT and in mild simple steatosis (SS) and NASH in VAT. We observed higher WNT5A expression in SS compared to normal liver in SAT, and a peak of WNT5A expression in mild SS. To conclude, we reported increased SFRP5 mRNA expression in SAT and VAT of NAFLD-related to obesity subjects, suggesting an implication of the SFRP5-WNT5A pathway in NAFLD pathogenesis, probably due to the adipose tissue-liver axis. Since the mechanisms by which this potential interaction takes place remain elusive, more research in this field is needed.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Obesidade Mórbida , Tecido Adiposo/metabolismo , Dieta Redutora , Feminino , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Hepatopatia Gordurosa não Alcoólica/complicações , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Obesidade/complicações , Obesidade/genética , Obesidade/metabolismo , Obesidade Mórbida/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo
14.
Int J Mol Sci ; 23(17)2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-36077376

RESUMO

(1) Background: C1q TNF-related protein 3 (CTRP3) is an adipokine with anti-inflammatory and cardioprotective properties. In our study, we explored changes in serum CTRP3 and its gene expression in epicardial (EAT) and subcutaneous (SAT) adipose tissue in patients with and without coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM) undergoing elective cardiac surgery. (2) Methods: SAT, EAT, and blood samples were collected at the start and end of surgery from 34 patients: (i) 11 without CAD or T2DM, (ii) 14 with CAD and without T2DM, and (iii) 9 with both CAD and T2DM. mRNA levels of CTRP3 were assessed by quantitative reverse transcription PCR. Circulating levels of CTRP3 and other factors were measured using ELISA and Luminex Multiplex commercial kits. (3) Results: Baseline plasma levels of TNF-α and IL6 did not differ among the groups and increased at the end of surgery. Baseline circulating levels of CTRP3 did not differ among the groups and decreased after surgery. In contrast, baseline CTRP3 mRNA levels in EAT were significantly decreased in CAD/T2DM group, while no differences were found for TNF-α and IL6 gene expression. (4) Conclusions: Our data suggest that decreased EAT mRNA levels of CTRP3 could contribute to higher risk of atherosclerosis in patients with CAD and T2DM.


Assuntos
Procedimentos Cirúrgicos Cardíacos , Doença da Artéria Coronariana , Diabetes Mellitus Tipo 2 , Tecido Adiposo/metabolismo , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/cirurgia , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirurgia , Humanos , Interleucina-6/metabolismo , Pericárdio/metabolismo , RNA Mensageiro/metabolismo , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
15.
Int J Mol Sci ; 23(17)2022 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-36077447

RESUMO

Obesity has become an extensive threat to human health due to associated chronic inflammation and metabolic diseases. Apoptosis-associated speck-like protein (ASC) is a critical link between inflammasome and apoptosis-inducing proteins. In this study, we aimed to clarify the role of ASC in lipid metabolism. With high-fat diet (HFD) and knockout leptin gene mice (ob/ob), we found that ASC expression in subcutaneous adipose tissue (SAT) correlated with obesity. It could also positively regulate the reprogramming of cellular energy metabolism. Stromal vascular fractions (SVF) cells derived from the SAT of Asc-/- mice or SVF from wild-type (WT) mice transfected with ASC siRNA were used to further investigate the underlying molecular mechanisms. We found ASC deficiency could lead to lipogenesis and inhibit lipolysis in SAT, aggravating lipid accumulation and impairing metabolic balance. In addition, our results showed that p53 and AMPKα expression were inhibited in SAT when ASC level was low. p53 and AMP-activated protein kinase α (AMPKα) were then assessed to elucidate whether they were downstream of ASC in regulating lipid metabolism. Our results revealed that ASC deficiency could promote lipid accumulation by increasing lipogenesis and decreasing lipolysis through p53/AMPKα axis. Regulation of ASC on lipid metabolism might be a novel therapeutic target for obesity.


Assuntos
Lipogênese , Lipólise , Proteínas Quinases Ativadas por AMP/metabolismo , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Lipídeos , Lipogênese/genética , Lipólise/fisiologia , Camundongos , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
16.
Cells ; 11(17)2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36078104

RESUMO

Obesity is a major risk factor for both metabolic and cardiovascular disease. We reported that, in obese male mice, histone deacetylase 9 (HDAC9) is upregulated in adipose tissues, and global deletion of HDAC9 protected against high fat diet (HFD)-induced obesity and metabolic disease. Here, we investigated the impact of adipocyte-specific HDAC9 gene deletion on diet-induced obesity in male and female mice. The HDAC9 gene expression was increased in adipose tissues of obese male and female mice and HDAC9 expression correlated positively with body mass index in humans. Interestingly, female, but not male, adipocyte-specific HDAC9 KO mice on HFD exhibited reduced body weight and visceral adipose tissue mass, adipocyte hypertrophy, and improved insulin sensitivity, glucose tolerance and adipogenic differentiation gene expression. Furthermore, adipocyte-specific HDAC9 gene deletion in female mice improved metabolic health as assessed by whole body energy expenditure, oxygen consumption, and adaptive thermogenesis. Mechanistically, compared to female mice, HFD-fed male mice exhibited preferential HDAC9 expression in the stromovascular fraction, which may have offset the impact of adipocyte-specific HDAC9 gene deletion in male mice. These results suggest that HDAC9 expressed in adipocytes is detrimental to obesity in female mice and provides novel evidence of sex-related differences in HDAC9 cellular expression and contribution to obesity-related metabolic disease.


Assuntos
Doenças Metabólicas , Obesidade , Tecido Adiposo/metabolismo , Animais , Dieta Hiperlipídica/efeitos adversos , Feminino , Histona Desacetilases , Humanos , Doenças Metabólicas/genética , Camundongos , Camundongos Obesos , Obesidade/metabolismo , Proteínas Repressoras
17.
BMC Endocr Disord ; 22(1): 224, 2022 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-36071485

RESUMO

BACKGROUND OF STUDY: Globally, many reproductive aged women are affected by polycystic ovarian syndrome (PCOS), which is a common endocrine and metabolic disorder that is linked with adipose dysfunction and chronic low-grade inflammation. Spironolactone (SPL), a mineralocorticoid receptor blocker has been documented as a metabolic modulator. However, its immunomodulatory effect in PCOS is unknown. Therefore, the present study hypothesized that SPL would ameliorate adipose dysfunction and inflammation in experimental PCOS animals. MATERIALS AND METHODS: Female Wistar rats that were 8 weeks old were allocated into three groups. Group 1 received vehicle (distilled water; p.o.), group 2 received letrozole (1 mg/kg; p.o.) and group 3 received letrozole plus SPL (0.25 mg/kg, p.o.). The administration was performed once daily for 21 days. RESULTS: The experimental PCOS animals showed insulin resistance, hyperinsulinemia and hyperandrogenism as well as oxidative stress and elevated inflammatory biomarkers (NF-kB/TNF-/IL-6) as well as a significant decrease in triglycerides, total cholesterol, free fatty acids, GSH and G6PD in the adipose tissue of PCOS animals. In addition, immunohistochemical assessment of adipose tissue showed significant expression of BAX and inflammasome, indicating apoptosis and inflammation compared to control animals. Nevertheless, administration of SPL attenuated these perturbations. CONCLUSION: Altogether, the present study suggests that low-dose spironolactone confers protection against adipose dysfunction in experimental PCOS animals by attenuating inflammation, oxidative stress and cellular apoptosis.


Assuntos
Síndrome do Ovário Policístico , Tecido Adiposo/metabolismo , Animais , Apoptose , Feminino , Humanos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Letrozol/efeitos adversos , Síndrome do Ovário Policístico/induzido quimicamente , Síndrome do Ovário Policístico/tratamento farmacológico , Síndrome do Ovário Policístico/metabolismo , Ratos , Ratos Wistar , Espironolactona/efeitos adversos
18.
Front Immunol ; 13: 998947, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36091076

RESUMO

Hepatic glucose production (HGP) is fine-regulated via glycogenolysis or gluconeogenesis to maintain physiological concentration of blood glucose during fasting-feeding cycle. Aberrant HGP leads to hyperglycemia in obesity-associated diabetes. Adipose tissue cooperates with the liver to regulate glycolipid metabolism. During these processes, adipose tissue macrophages (ATMs) change their profiles with various physio-pathological settings, producing diverse effects on HGP. Here, we briefly review the distinct phenotypes of ATMs under different nutrition states including feeding, fasting or overnutrition, and detail their effects on HGP. We discuss several pathways by which ATMs regulate hepatic gluconeogenesis or glycogenolysis, leading to favorable or unfavorable metabolic consequences. Furthermore, we summarize emerging therapeutic targets to correct metabolic disorders in morbid obesity or diabetes based on ATM-HGP axis. This review puts forward the importance and flexibility of ATMs in regulating HGP, proposing ATM-based HGP modulation as a potential therapeutic approach for obesity-associated metabolic dysfunction.


Assuntos
Diabetes Mellitus , Glucose , Tecido Adiposo/metabolismo , Diabetes Mellitus/metabolismo , Glucose/metabolismo , Humanos , Fígado/metabolismo , Macrófagos/metabolismo , Obesidade/metabolismo
19.
BMC Genomics ; 23(1): 644, 2022 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-36085018

RESUMO

BACKGROUND: Donkey meat has low fat and high protein contents and is rich in various unsaturated fatty acids and trace elements that are beneficial to human digestion and absorption. IMF (intramuscular fat), also known as marbling, is an important indicator of the lean meat to fat ratio, which directly affects the tenderness and juiciness of the meat. At present, the underlying molecular variations affecting IMF content among donkey breeds are unclear. The Guangling donkey is an indigenous species in China. This study explored candidate regulatory genes that affect IMF content in Guangling donkeys. The IMF content of the longissimus dorsi muscle in 30 Guangling donkeys was measured. Six donkeys of similar age were selected according to age factors and divided into two groups, the high (H) and low (L) fat groups, according to their IMF content. RESULTS: RNA-seq technology was used to compare the muscle transcriptome between the two groups. More than 75.0% of alternative splicing (AS) events were of the skipped exon (SE) type. A total of 887 novel genes were identified; only 386 novel genes were aligned to the annotation information of various databases. Transcriptomics analysis revealed 167 differentially expressed genes (DEGs), of which 64 were upregulated and 103 were downregulated between the H and L groups. Gene ontology analysis showed that the DEGs were enriched in multiple biological processes and pathways that are related to adipocyte differentiation, lipid synthesis, and neutral lipid metabolism. KEGG pathway analysis suggested that arachidonic acid metabolism, the HIF-1 signalling pathway, fructose and mannose metabolism, glycerophospholipid metabolism, and the AMPK signalling pathway were involved in lipid deposition. In addition, a gene-gene interaction network was constructed that revealed that the DEGs, including SCD, LEPR, CIDEA, DLK1, DGAT2, ITGAL, HMOX1, WNT10B, and DGKA, had significant roles in adipocyte differentiation and adipogenesis. The selected DEGs were further validated by qRT-PCR. CONCLUSION: This study improves the in-depth understanding of gene regulation and protein expression regarding IMF deposition and lays a basis for subsequent molecular breeding studies in Guangling donkeys.


Assuntos
Equidae , Transcriptoma , Tecido Adiposo/metabolismo , Animais , Equidae/genética , Perfilação da Expressão Gênica , Humanos , Lipídeos , Músculos Paraespinais
20.
Mol Cells ; 45(9): 649-659, 2022 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-36058890

RESUMO

A long-term energy nutritional imbalance fundamentally causes the development of obesity and associated fat accumulation. Lysosomes, as nutrient-sensing and lipophagy centers, critically control cellular lipid catabolism in response to nutrient deprivation. However, whether lysosome activity is directly involved in nutrient-induced fat accumulation remains unclear. In this study, worm fat accumulation was induced by 1 mM glucose or 0.02 mM palmitic acid supplementation. Along with the elevation of fat accumulation, lysosomal number and acidification were also increased, suggesting that lysosome activity might be correlated with nutrient-induced fat deposition in Caenorhabditis elegans. Furthermore, treatments with the lysosomal inhibitors chloroquine and leupeptin significantly reduced basal and nutrient-induced fat accumulation in C. elegans. The knockdown of hlh-30, which is a critical gene in lysosomal biogenesis, also resulted in worm fat loss. Finally, the mutation of aak-2, daf-15, and rsks-1 showed that mTORC1 (mechanistic target of rapamycin complex-1) signaling mediated the effects of lysosomes on basal and nutrient-induced fat accumulation in C. elegans. Overall, this study reveals the previously undescribed role of lysosomes in overnutrition sensing, suggesting a new strategy for controlling body fat accumulation.


Assuntos
Proteínas de Caenorhabditis elegans , Caenorhabditis elegans , Tecido Adiposo/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/metabolismo , Lisossomos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , Nutrientes
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...