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1.
Phys Med Rehabil Clin N Am ; 34(1): 25-47, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36410885

RESUMO

In recent years, autologous biological preparations have emerged as a growing area of medical innovation in interventional orthopedical procedures and surgical interventions. These cellular therapies are often referred to as orthobiologics and are derived from patient's own tissues, like blood, bone marrow, and adipose tissue to prepare platelet-rich plasma (PRP), bone marrow concentrate (BMC), and adipose tissue concentrate (ATC), respectively. In this article, we emphasize and discuss the physiologic variability of autologous prepared BMC and ATC for the delivery of mesenchymal stem cells to support tissue repair processes.


Assuntos
Transplante de Células-Tronco Hematopoéticas , Células-Tronco Mesenquimais , Plasma Rico em Plaquetas , Humanos , Medula Óssea , Tecido Adiposo
2.
Phys Med Rehabil Clin N Am ; 34(1): 63-70, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36410891

RESUMO

Orthobiologics have shown immense treatment potential in many medical fields including sports medicine, musculoskeletal disorders, and pain management. As with the case of any medical procedures and treatments, there are potential side effects or caveats that physicians and patients should be cognizant of. Nevertheless, the use of orthobiologics does not seem to have consistent severe side effects and do not have increased risks with transmissible disease, immune-modulated reactions, or oncologic processes.


Assuntos
Doenças Musculoesqueléticas , Medicina Esportiva , Humanos , Doenças Musculoesqueléticas/terapia
3.
J Clin Transl Hepatol ; 11(1): 58-66, 2023 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-36406322

RESUMO

Background and Aims: Emerging evidence has demonstrated that abnormal body composition may potentiate the development of frailty, whereas little work focuses on the role of divergent adipose tissue. Therefore, we aimed to determine the potential contribution of adipose tissue distribution to multidimensional frailty in decompensated cirrhosis. Methods: We conducted a retrospective cohort study. Divergent adipose tissues were assessed by computed tomography-derived subcutaneous adipose tissue index (SATI), visceral adipose tissue index (VATI) and total adipose tissue index (TATI), respectively. Frailty was identified by our validated self-reported Frailty Index. Multiple binary logistic models incorporating different covariates were established to assess the relationship between adipose tissue distribution and frailty. Results: The study cohort comprised 245 cirrhotic patients with 45.3% being male. The median Frailty Index, body mass index (BMI) and model for end-stage liver disease (MELD) score were 0.11, 24.3 kg/m2 and 8.9 points, respectively. In both men and women, patients who were frail exhibited lower levels of SATI in comparison with nonfrail patients. SATI inversely correlated with Frailty Index in the entire cohort (rs=-0.1361, p=0.0332). Furthermore, SATI or TATI was independently associated with frail phenotype in several multiple logistic regression models adjusting for age, BMI, presence of ascites, sodium, Child-Pugh class or MELD score in isolation. Conclusions: In the context of decompensated cirrhosis, low SATI and concomitant TATI were associated with higher risk of being frail. These findings highlight the importance to further apply tissue-specific tools of body composition in place of crude metric like BMI.

4.
Methods Mol Biol ; 2598: 75-85, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36355286

RESUMO

Adipose-derived stromal cells (ASC) are a promising alternative cell source to chondrocytes as well as to bone marrow-derived mesenchymal stromal cells (BMSC) in cartilage tissue engineering and repair. Here we describe ASC isolation from liposuction by-products by collagenase-based tissue digestion combined with cell filtration and followed by monolayer attachment and expansion culture. Quality control requires confirmation of correct surface marker expression and multilineage differentiation potential by a trilineage differentiation assay.


Assuntos
Tecido Adiposo , Condrogênese , Diferenciação Celular , Células Estromais/metabolismo , Cartilagem , Condrócitos , Células Cultivadas , Células da Medula Óssea
5.
J Ethnopharmacol ; 302(Pt A): 115700, 2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36126782

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Obesity is a critical threat to global health, and brown adipose tissue (BAT) is a potential target for the treatment of obesity and comorbidities. Xuezhikang Capsule (XZK), an extract of red yeast rice, has remarkable clinical efficacy and is widely used for the treatment of hyperlipidemia and coronary heart disease. However, its modulatory effect on BAT remains unknown. AIM OF THIS STUDY: The aim of this study was to investigate the protective mechanism of XZK in the obese spontaneously hypertensive rat (SHR) model by evaluating the regulatory effect of XZK on the BAT gene profile through transcriptome sequencing. MATERIALS AND METHODS: The SHRs were randomly divided into four groups: the standard chow diet (STD) group, the STD supplemented with 126 mg/kg of XZK group, the high-fat diet (HFD) group, and the HFD supplemented with 126 mg/kg of XZK group. All SHRs were fed for 18 weeks. The metabolic phenotypes, including body weight, fat mass, oral glucose tolerance test (OGTT), and serum glucose and lipid levels, was evaluated, and hematoxylin and eosin staining (H&E) staining was performed to evaluate the adipose tissue histopathological phenotype. Transcriptome sequencing was performed to determine the mechanism by which XZK improves the metabolic phenotype and the expression of key differential expression genes was verified by real-time quantitative polymerase chain reaction (qRT-PCR). RESULTS: XZK inhibited HFD-induced weight gain and adipose tissue remodeling in SHRs and prevented hypertrophy of epididymal adipocytes and maintained the brown fat phenotype. XZK intervention also improved glucose and lipid metabolism in SHRs, as suggested by a reduction in serum triglyceride (TG), low-density cholesterol (LDL-C), and fasting blood glucose (FBG) levels as well as increasing in serum high-density cholesterol (HDL-C) levels. Transcriptome sequencing analysis confirmed the regulatory effect of XZK on the gene expression profile of BAT, and the expression patterns of 45 genes were reversed by the XZK intervention. Additionally, the results of the transcriptome analysis of 10 genes that are important for brown fat function were in line with the results of qRT-PCR. CONCLUSIONS: XZK protected SHRs from HFD-induced obesity, inhibited fat accumulation and improved glucolipid metabolism. Additionally, the protective effect of XZK on the overall metabolism of obese SHRs might partly be related to its regulatory effect on the BAT gene expression profile. These findings might provide novel therapeutic strategies for obesity-related metabolic diseases in traditional Chinese medicine (TCM).

6.
J Nutr Biochem ; 111: 109153, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36150680

RESUMO

This study aimed to characterize the potential beneficial effects of chronic docosahexaenoic acid (DHA) supplementation on restoring subcutaneous white adipose tissue (scWAT) plasticity in obese aged female mice. Two-month-old female C57BL/6J mice received a control (CT) or a high fat diet (HFD) for 4 months. Then, 6-month-old diet-induced obese (DIO) mice were distributed into the DIO and the DIOMEG group (fed with a DHA-enriched HFD) up to 18 months. In scWAT, the DHA-enriched diet reduced the mean adipocyte size and reversed the upregulation of lipogenic genes induced by the HFD, reaching values even lower than those observed in CT animals. DIO mice exhibited an up-regulation of lipolytic and fatty oxidation gene expressions that was reversed in DHA-supplemented mice except for Cpt1a mRNA levels, which were higher in DIOMEG as compared to CT mice. DHA restored the increase of proinflammatory genes observed in scWAT of DIO mice. While no changes were observed in total macrophage F4/80+/CD11b+ content, the DHA treatment switched scWAT macrophages profile by reducing the M1 marker Cd11c and increasing the M2 marker CD206. These events occurred alongside with a stimulation of beige adipocyte specific genes, the restoration of UCP1 and pAKT/AKT ratio, and a recovery of the HFD-induced Fgf21 upregulation. In summary, DHA supplementation induced a metabolic remodeling of scWAT to a healthier phenotype in aged obese mice by modulating genes controlling lipid accumulation in adipocytes, reducing the inflammatory status, and inducing beige adipocyte markers in obese aged mice.


Assuntos
Ácidos Docosa-Hexaenoicos , Obesidade , Feminino , Camundongos , Animais , Camundongos Obesos , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Obesidade/metabolismo , Camundongos Endogâmicos C57BL , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gordura Subcutânea/metabolismo , Suplementos Nutricionais , Tecido Adiposo/metabolismo
7.
J Nutr Biochem ; 111: 109159, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36162565

RESUMO

Obesity and metabolic disorders are threats to human health. Extracellular matrix (ECM) is an important member of adipose microenvironment. ECM remodeling contributes to obesity and insulin resistance, but the roles of every single ECM component is still not fully understood. We observed glucose and lipids metabolic disorders in high-fat diet (HFD)-fed mice and humans with obesity. Higher levels of inflammatory factors and hormones existed in serum of HFD-fed mice. Multiple collagens, laminins, fibronectin, nidogen, and Hspg2 were upregulated in obese white adipose tissue (WAT) from mice and humans. These effects were stronger in subcutaneous WAT than visceral WAT in mice, but the fat depot difference was reversed in humans. The ECM structure and the morphology of adipocytes seeded on ECM were changed in the HFD group. In human visceral WAT, ECM genes showed positive correlations with blood lipids and glucose. In vitro, collagen I/IV and LAMA4 proteins showed similar changes with C/EBPα during the differentiation of adipocytes. Macromolecular crowders (MMC) promoted partial collagen and non-collagen gene expression. Oleic acid (OA) and MMC upregulated collagen I/IV and LAMA4 proteins, and the effects of MMC were stronger than that of OA. Moreover, MMC promoted the differentiation of adipocytes, but OA increased the size of lipid droplets. Positive correlations were observed between ECM genes and adipogenesis-related genes in adipocytes. In conclusion, some obesogens (such as HFD) induce ECM remodeling, and the upregulation of ECM components is closely related to adipogenesis, suggesting that adipose ECM deposition is an indicator of obesity and metabolic disorders.


Assuntos
Resistência à Insulina , Obesidade , Camundongos , Humanos , Animais , Obesidade/metabolismo , Tecido Adiposo Branco/metabolismo , Dieta Hiperlipídica/efeitos adversos , Adipogenia , Matriz Extracelular , Glucose/metabolismo , Lipídeos , Camundongos Endogâmicos C57BL
8.
Cytokine ; 161: 156080, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36368230

RESUMO

OBJECTIVE: Interleukin-33 (IL-33) is associated with obesity-related inflammation. We aim to investigate IL-33 expression in subcutaneous adipose tissue (SAT) in type 2 diabetes (T2D) subjects and its effects on human adipocyte glucose uptake. METHODS: Expression of IL-33 was analysed in SAT from cohort studies including subjects with and without obesity and T2D and correlated with insulin resistance and obesity markers. Magnetic resonance imaging (MRI) of tissue fat volumes was performed. We investigated the effects of IL-33 treatment on ex vivo adipocyte glucose uptake. RESULTS: T2D subjects had higher IL-33 gene and protein expression in SAT than the control subjects. IL-33 mRNA expression was positively correlated with markers of dysglycemia (e.g. HbA1c), insulin resistance (e.g. HOMA-IR) and adiposity (BMI, visceral adipose tissue volume, liver and pancreas fat %). In multiple linear regression analyses, insulin resistance and T2D status were the strongest predictors of IL-33, independent of BMI. IL-33 mRNA expression was negatively correlated with expression of genes regulating adipocyte glucose uptake, lipid storage, and adipogenesis (e.g.glucose transporter 1 and 4 (GLUT1/4), fatty acid binding protein 4 (FABP4), and PPARG). Additionally, incubation of SAT with IL-33 reduced adipocyte glucose uptake and GLUT4 gene and protein expression. CONCLUSIONS: Our findings suggest that T2D subjects have higher IL-33 gene and protein expressionin SATthan control subjects, which is associated with insulin resistance and reduced gene expression of lipid storage and adipogenesis markers. IL-33 may reduce adipocyte glucose uptake. This opens up a potential pharmacological route for reversing insulin resistance in T2D and prediabetes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Humanos , Diabetes Mellitus Tipo 2/metabolismo , Interleucina-33/metabolismo , Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Obesidade/metabolismo , Glucose/metabolismo , RNA Mensageiro/metabolismo , Lipídeos
9.
J Nutr Biochem ; 111: 109175, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36223834

RESUMO

Increased body iron stores and inflammation in adipose tissue have been implicated in the pathogenesis of insulin resistance (IR) and type 2 diabetes mellitus. However, the underlying basis of these associations is unclear. To attempt to investigate this, we studied the development of IR and associated inflammation in adipose tissue in the presence of increased body iron stores. Male hepcidin knock-out (Hamp1-/-) mice, which have increased body iron stores, and wild-type (WT) mice were fed a high-fat diet (HFD) for 12 and 24 weeks. Development of IR and metabolic parameters linked to this, insulin signaling in various tissues, and inflammation and iron-related parameters in visceral adipose tissue were studied in these animals. HFD-feeding resulted in impaired glucose tolerance in both genotypes of mice. In response to the HFD for 24 weeks, Hamp1-/- mice gained less body weight and developed less systemic IR than corresponding WT mice. This was associated with less lipid accumulation in the liver and decreased inflammation and lipolysis in the adipose tissue in the knock-out mice, than in the WT animals. Fewer macrophages infiltrated the adipose tissue in the knockout mice than in wild-type mice, with these macrophages exhibiting a predominantly anti-inflammatory (M2-like) phenotype and indirect evidence of a possible lowered intracellular iron content. The absence of hepcidin was thus associated with attenuated inflammation in the adipose tissue and increased whole-body insulin sensitivity, suggesting a role for it in these processes.


Assuntos
Diabetes Mellitus Tipo 2 , Resistência à Insulina , Masculino , Camundongos , Animais , Resistência à Insulina/fisiologia , Dieta Hiperlipídica/efeitos adversos , Hepcidinas/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Camundongos Endogâmicos C57BL , Tecido Adiposo/metabolismo , Inflamação/metabolismo , Insulina/metabolismo , Camundongos Knockout , Ferro/metabolismo
10.
J Nutr Biochem ; 111: 109173, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36228975

RESUMO

The antidiabetic effects of green tea have been demonstrated in clinical trials and epidemiological studies. This study investigated the antidiabetic effects of green tea extract (GTE) and its underlying molecular mechanisms using a leptin receptor-deficient db/db mouse model (Leprdb/db). Treatment with GTE for 2 weeks improved glucose tolerance and insulin sensitivity in Leprdb/db mice. In addition, GTE treatment reduced the body weight and adiposity of Leprdb/db mice. Furthermore, GTE treatment reduced pro-inflammatory gene expression, including nuclear factor kappa B (NF-κB) in white adipose tissue (WAT), and also reduced dipeptidyl peptidase-4 (DPP4) expression levels in WAT as well as in the serum. The promoter region of Dpp4 contains the NF-κB binding site, and DPP4 was found to be a direct target of NF-κB. Consistently, in vitro treatment of cells with GTE or its main constituent epigallocatechin gallate reduced lipopolysaccharide-induced NF-κB/DPP4 expression in 3T3-L1 adipocytes and RAW264.7 cells. Overall, our data demonstrated that GTE exerts an anti-diabetic effect by regulating the expression levels of NF-κB and DPP4 in WAT.


Assuntos
Dipeptidil Peptidase 4 , Hipoglicemiantes , Camundongos , Animais , Hipoglicemiantes/farmacologia , Hipoglicemiantes/uso terapêutico , Hipoglicemiantes/metabolismo , Dipeptidil Peptidase 4/genética , Dipeptidil Peptidase 4/metabolismo , NF-kappa B/metabolismo , Extratos Vegetais/uso terapêutico , Tecido Adiposo/metabolismo , Chá/química
11.
Food Chem ; 404(Pt A): 134405, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36444031

RESUMO

Several factors can impact the gut microbiota, affecting host metabolism and immunity. It implies intestinal barrier disruption and translocation of gut microbiota metabolites to the bloodstream, such as lipopolysaccharides (LPS). LPS is an endotoxin from gram-negative gut bacteria that trigger the activation of the Toll-like receptor-4 (TLR-4) inflammatory pathway and can modulate white adipose tissue (WAT) metabolism. Dietary components, including diets rich in fiber and polyphenols, contribute to intestinal environment homeostasis. Grape seed proanthocyanidins extract (GSPE) may improve intestinal permeability and microbial diversity and increase short-chain fatty acids production. Furthermore, GSPE has been involved in LPS reduction, down-regulating the TLR-4 pathway, decreasing the WAT metainflammatory profile, and preventing adipocyte hypertrophy. Studies have pointed out strategies to promote health and control obesity by modulating the gut microbiota environment. Therefore, this review aims to summarize the potential effects of GSPE on the gut microbiota-white adipose tissue axis against obesity.


Assuntos
Microbioma Gastrointestinal , Proantocianidinas , Vitis , Receptor 4 Toll-Like , Lipopolissacarídeos , Promoção da Saúde , Tecido Adiposo Branco , Fibras na Dieta , Obesidade
12.
Pediatr Int ; 64(1): e15323, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36331224

RESUMO

BACKGROUND: Patients with nephrotic syndrome (NS) are at a high risk of cardiovascular disease, obesity, and dyslipidemia. The aim of this study was to evaluate the formation of epicardial adipose tissue (EAT) and investigate electrocardiographic (ECG) parameters in patients. METHODS: Thirty-two patients aged 0-18 years and 15 control patients were compared. In the patient group, physical examination and laboratory parameters were recorded. Atrial depolarization and ventricular repolarization parameters in ECG were compared between the groups. EAT was evaluated with M-mode measurements on echocardiography. RESULTS: There was no difference between the groups in terms of sex, age, body mass index, systolic and diastolic BP. EAT was found to be significantly higher in the patient group. In ECG evaluations it was determined that atrial depolarization and ventricular repolarization parameters increased in the patient group. CONCLUSIONS: Cardiovascular morbidity and mortality are high in kidney diseases. Measurement and follow-up of EAT and ECG findings as a noninvasive parameter can provide information in NS.


Assuntos
Síndrome Nefrótica , Humanos , Síndrome Nefrótica/complicações , Síndrome Nefrótica/diagnóstico , Pericárdio/diagnóstico por imagem , Tecido Adiposo/diagnóstico por imagem , Ecocardiografia , Arritmias Cardíacas
13.
Temperature (Austin) ; 9(4): 310-317, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339088

RESUMO

Thermoregulation is critical in health and disease and is tightly controlled to maintain body temperature homeostasis. Carbon monoxide (CO), an endogenous gasotransmitter produced during heme degradation by heme oxygenases, has been suggested to play a role in body core temperature (Tb) regulation. However, a direct involvement of CO in thermoregulation has not been confirmed and its mechanism(s) of action remain largely unknown. In the present study we characterized the effects of systemic delivery of CO by administration of an orally active CO-releasing molecule (CORM-401) on Tb regulation in conscious freely moving rats. Specifically, we evaluated the main thermo effectors in rats treated with CORM-401 by assessing: (i) non-shivering thermogenesis, i.e. the increased metabolism of brown fat measured through oxygen consumption and (ii) the rate of heat loss from the tail through calculations of heat loss index. We found that oral administration of CORM-401 (30 mg/kg) resulted in augmented CO delivery into the blood circulation as evidenced a by significant increase in carbon monoxy hemoglobin levels(COHb). In addition, treatment with CORM-401 increased Tb, which was caused by an elevated non-shivering thermogenesis indicated by increased oxygen consumption without significant changes in the tail heat loss. On the other hand, CORM-401 did not affect blood pressure, but significantly decreased heart rate. In summary, the findings of the present study reveal that increased circulating CO levels lead to a rise in Tb, which could have important implications in the emerging role of CO in the modulation of energetic metabolism.

14.
Front Public Health ; 10: 1023935, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339142

RESUMO

Background: Coronavirus Disease 2019 (COVID-19) has rapidly evolved as a global pandemic. Observational studies found that visceral adipose tissue (VAT) increased the likelihood of worse clinical outcomes in COVID-19 patients. Whereas, whether VAT is causally associated with the susceptibility, hospitalization, or severity of COVID-19 remains unconfirmed. We aimed to investigate the causal associations between VAT and susceptibility, hospitalization, and severity of COVID-19. Methods: We applied a two-sample Mendelian randomization (MR) study to infer causal associations between VAT and COVID-19 outcomes. Single-nucleotide polymorphisms significantly associated with VAT were derived from a large-scale genome-wide association study. The random-effects inverse-variance weighted method was used as the main MR approach, complemented by three other MR methods. Additional sensitivity analyses were also performed. Results: Genetically predicted higher VAT mass was causally associated with higher risks of COVID-19 susceptibility [odds ratios (ORs) = 1.13; 95% confidence interval (CI), 1.09-1.17; P = 4.37 × 10-12], hospitalization (OR = 1.51; 95% CI = 1.38-1.65; P = 4.14 × 10-20), and severity (OR = 1.58; 95% CI = 1.38-1.82; P = 7.34 × 10-11). Conclusion: This study provided genetic evidence that higher VAT mass was causally associated with higher risks of susceptibility, hospitalization, and severity of COVID-19. VAT can be a useful tool for risk assessment in the general population and COVID-19 patients, as well as an important prevention target.


Assuntos
COVID-19 , Humanos , COVID-19/epidemiologia , Gordura Intra-Abdominal , Análise da Randomização Mendeliana , Estudo de Associação Genômica Ampla , Hospitalização
15.
Front Med (Lausanne) ; 9: 1023583, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36341262

RESUMO

Background: To better understand the patient's heterogeneity in fatty liver disease (FLD), metabolic dysfunction-associated fatty liver disease (MAFLD) was proposed by international experts as a new nomenclature for nonalcoholic fatty liver disease (NAFLD). We aimed to evaluate the cardiovascular risk, assessed through coronary artery calcium (CAC) and epicardial adipose tissue (EAT), of patients without FLD and patients with FLD and its different subtypes. Methods: Cross sectional study of 370 patients. Patients with FLD were divided into 4 groups: FLD without metabolic dysfunction (non-MD FLD), MAFLD and the presence of overweight/obesity (MAFLD-OW), MAFLD and the presence of two metabolic abnormalities (MAFLD-MD) and MAFLD and the presence of T2D (MAFLD-T2D). MAFLD-OW included two subgroups: metabolically healthy obesity (MHO) and metabolically unhealthy obesity (MUHO). The patients without FLD were divided into 2 groups: patients without FLD and without MD (non-FLD nor MD; reference group) and patients without FLD but with MD (non-FLD with MD). EAT and CAC (measured through the Agatston Score) were determined by computed tomography. Results: Compared with the reference group (non-FLD nor MD), regarding EAT, patients with MAFLD-T2D and MAFLD-MUHO had the highest risk for CVD (OR 15.87, 95% CI 4.26-59.12 and OR 17.60, 95% CI 6.71-46.20, respectively), patients with MAFLD-MHO were also at risk for CVD (OR 3.62, 95% CI 1.83-7.16), and patients with non-MD FLD did not have a significantly increased risk (OR 1.77; 95% CI 0.67-4.73). Regarding CAC, patients with MAFLD-T2D had an increased risk for CVD (OR 6.56, 95% CI 2.18-19.76). Patients with MAFLD-MUHO, MAFLD-MHO and non-MD FLD did not have a significantly increased risk compared with the reference group (OR 2.54, 95% CI 0.90-7.13; OR 1.84, 95% CI 0.67-5.00 and OR 2.11, 95% CI 0.46-9.74, respectively). Conclusion: MAFLD-T2D and MAFLD-OW phenotypes had a significant risk for CVD. MAFLD new criteria reinforced the importance of identifying metabolic phenotypes in populations as it may help to identify patients with higher CVD risk and offer a personalized therapeutic management in a primary prevention setting.

16.
Radiol Phys Technol ; 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36344662

RESUMO

The purpose of this study was to realize an automated volume measurement of abdominal adipose tissue from the entire abdominal cavity in Dixon magnetic resonance (MR) images using deep learning. Our algorithm involves a combination of extraction of the abdominal cavity and body trunk regions using deep learning and extraction of a fat region based on automatic thresholding. To evaluate the proposed method, we calculated the Dice coefficient (DC) between the extracted regions using deep learning and labeled images. We also compared the visceral adipose tissue (VAT) and subcutaneous adipose tissue volumes calculated by employing the proposed method with those calculated from computed tomography (CT) images scanned on the same day using the automatic calculation method previously developed by our group. We implemented our method as a plug-in in a web-based medical image processing platform. The DCs of the abdominal cavity and body trunk regions were 0.952 ± 0.014 and 0.995 ± 0.002, respectively. The VAT volume measured from MR images using the proposed method was almost equivalent to that measured from CT images. The time required for our plug-in to process the test set was 118.9 ± 28.0 s. Using our proposed method, the VAT volume measured from MR images can be an alternative to that measured from CT images.

17.
Artigo em Inglês | MEDLINE | ID: mdl-36351253

RESUMO

BACKGROUND: Typical vivarium temperatures (20-26°C) induce facultative thermogenesis in mice, a process attributable in part to uncoupling protein-1 (UCP1). The impact of modest changes in housing temperature on whole body and adipose tissue energetics in mice remains unclear. Here, we determined the effects of transitioning mice from 24°C to 30°C on total energy expenditure and adipose tissue protein signatures. METHODS: C57BL/6J mice were housed at 24°C for two weeks and then either remained at 24°C (n=16 per group, 8M/8F) or were transitioned to 30°C (n=16 per group, 8M/8F) for 4 weeks. Total energy expenditure and its components were determined by indirect calorimetry. Interscapular brown adipose tissue (iBAT) and inguinal white adipose tissue (iWAT) proteins were quantified by western blot and quantitative proteomics. RESULTS: Transitioning from 24°C to 30°C reduced total energy expenditure in both male (-25%) and female (-16%) mice, which was attributable to 36% and 40% decreases in basal energy expenditure in males and females, respectively. Total iBAT UCP1 protein content was 50% lower at 30°C compared to 24°C, whereas iWAT UCP1 protein content was similar between conditions. iBAT UCP1 protein content remained 20-fold greater than iWAT at 30°C. 183 and 41 proteins were differentially expressed between 24°C and 30°C in iBAT and iWAT, respectively. 257 iWAT proteins differentially expressed between sexes at 30°C were not differentially expressed at 24°C. SUMMARY: 30°C housing lowers total energy expenditure of mice when compared to an ambient temperature (24°C) that falls within the National Research Council's guidelines for housing laboratory mice. Lower iBAT UCP1 content accompanied chronic housing at 30°C. Further, housing temperature influences sexual dimorphism in the iWAT proteome. These data have implications regarding the optimization of preclinical models of human disease.

18.
Artigo em Inglês | MEDLINE | ID: mdl-36351292

RESUMO

Adipose tissue dysfunction is a key mechanism that leads to adiposity-based chronic disease. This study aimed to investigate the feasibility of the adiponectin/leptin ratio (AdipoQ/Lep) as an adipose tissue and metabolic function biomarker in adults with obesity, without diabetes. Data were collected from a clinical trial conducted in 28 adults with obesity (mean body mass index: 35.4±3.7 kg/m2) (NCT02169778). Using a forward stepwise multiple linear regression model to explore the relationship between AdipoQ/Lep and HOMA-IR, it was observed that 48.6% of HOMA-IR variance was explained by triacylglycerols, AdipoQ/Lep and waist-to-hip ratio (P<0.001), being AdipoQ/Lep the strongest independent predictor (Beta = -0.449, P<0.001). A lower AdipoQ/Lep was correlated with a higher body mass index (Rs = -0.490, P<0.001), body fat mass (Rs = -0.486, P<0.001), waist-to-height ratio (RS = -0.290, P=0.037), and plasma resistin (Rs = -0.365, P=0.009). These data highlight the central role of adipocyte dysfunction in the pathogenesis of insulin resistance and emphasize that AdipoQ/Lep may be a promising early marker of insulin resistance development in adults with obesity.

19.
Artigo em Inglês | MEDLINE | ID: mdl-36351437

RESUMO

BACKGROUND: Cancer-associated cachexia (CAC) is a wasting syndrome drastically reducing efficacy of chemotherapy and life expectancy of patients. CAC affects up to 80% of cancer patients, yet the mechanisms underlying the disease are not well understood and no approved disease-specific medication exists. As a multiorgan disorder, CAC can only be studied on an organismal level. To cover the diverse aetiologies of CAC, researchers rely on the availability of a multifaceted pool of cancer models with varying degrees of cachexia symptoms. So far, no tumour model syngeneic to C57BL/6 mice exists that allows direct comparison between cachexigenic- and non-cachexigenic tumours. METHODS: MCA207 and CHX207 fibrosarcoma cells were intramuscularly implanted into male or female, 10-11-week-old C57BL/6J mice. Tumour tissues were subjected to magnetic resonance imaging, immunohistochemical-, and transcriptomic analysis. Mice were analysed for tumour growth, body weight and -composition, food- and water intake, locomotor activity, O2 consumption, CO2 production, circulating blood cells, metabolites, and tumourkines. Mice were sacrificed with same tumour weights in all groups. Adipose tissues were examined using high-resolution respirometry, lipolysis measurements in vitro and ex vivo, and radioactive tracer studies in vivo. Gene expression was determined in adipose- and muscle tissues by quantitative PCR and Western blotting analyses. Muscles and cultured myotubes were analysed histologically and by immunofluorescence microscopy for myofibre cross sectional area and myofibre diameter, respectively. Interleukin-6 (Il-6) was deleted from cancer cells using CRISPR/Cas9 mediated gene editing. RESULTS: CHX207, but not MCA207-tumour-bearing mice exhibited major clinical features of CAC, including systemic inflammation, increased plasma IL-6 concentrations (190 pg/mL, P ≤ 0.0001), increased energy expenditure (+28%, P ≤ 0.01), adipose tissue loss (-47%, P ≤ 0.0001), skeletal muscle wasting (-18%, P ≤ 0.001), and body weight reduction (-13%, P ≤ 0.01) 13 days after cancer cell inoculation. Adipose tissue loss resulted from reduced lipid uptake and -synthesis combined with increased lipolysis but was not associated with elevated beta-adrenergic signalling or adipose tissue browning. Muscle atrophy was evident by reduced myofibre cross sectional area (-21.8%, P ≤ 0.001), increased catabolic- and reduced anabolic signalling. Deletion of IL-6 from CHX207 cancer cells completely protected CHX207IL6KO -tumour-bearing mice from CAC. CONCLUSIONS: In this study, we present CHX207 fibrosarcoma cells as a novel tool to investigate the mediators and metabolic consequences of CAC in C57BL/6 mice in comparison to non-cachectic MCA207-tumour-bearing mice. IL-6 represents an essential trigger for CAC development in CHX207-tumour-bearing mice.

20.
Obes Rev ; : e13521, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36349390

RESUMO

Overweight and obesity, as a result of excess fat accumulation, have become a worldwide public health issue. Recent studies have shown that obesity is closely related to many human diseases, such as cancer, cardiovascular diseases, and type 2 diabetes mellitus, in which adipose tissue plays a dual role. In addition to thermal and mechanical insulation and a critical role in energy storage and heat production, adipose tissue is also a highly plastic endocrine and signaling organ that secretes multiple bioactive molecules for inter-organ crosstalk. The phenotypic and biological changes of adipose tissue under pathological conditions, especially in obesity, increase the challenge of deciphering the positive or negative effects of adipose tissue in disease. Despite numerous studies on obesity and adipose tissue, the ambiguous role of adipose tissue on specific organs or tissues in different diseases is not fully understood, and the definite mechanisms remain obscure. In this review, we first summarize the basic biological characteristics of adipose tissue in the physiological state and the abnormal remodeling of adipose tissue during obesity. We then discuss the complex and disparate effects of obesity on various human diseases, with a particular focus on the dual roles and underlying mechanisms of adipose tissue, a quintessential player in obesity, in this process. More importantly, rethinking the causes of the "obesity paradox" phenomenon in diseases from the perspective of adipose homeostasis and dysfunction provides a novel strategy for disease treatment by intervening in fat function.

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