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1.
Atherosclerosis ; 386: 117371, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-38029505

RESUMO

BACKGROUND AND AIMS: Individuals with a higher abdominal adipose tissue accumulation are at higher risk of developing cardiometabolic diseases. For a given body mass index (BMI), women typically present lower abdominal adipose tissue accumulation compared to men. Whether abdominal adiposity is a causal driver of cardiometabolic risk, or a mere marker of ectopic fat deposition is debated. METHODS: We investigated the sex-specific and sex-combined impact of height and BMI-adjusted gluteofemoral adipose tissue (GFATadj) adjusted abdominal subcutaneous adipose tissue (ASATadj) and adjusted visceral adipose tissue (VATadj) on cardiometabolic traits and diseases using Mendelian randomization. RESULTS: Leveraging genome-wide summary statistics on GFATadj, ASATadj and VATadj from 39,076 UK Biobank participants with full-body magnetic resonance imaging available, we found that GFATadj is associated with a more favourable cardiometabolic risk profile including lower low density lipoprotein (LDL) cholesterol, triglycerides, fasting glucose, fasting insulin, liver enzyme levels and blood pressure as well as higher high density lipoprotein (HDL) cholesterol levels. GFATadj also is negatively associated with ischemic stroke, coronary artery disease, type 2 diabetes, and non-alcoholic fatty liver disease (NAFLD). ASATadj is not associated with cardiometabolic traits and diseases, whereas VATadj is associated with liver fat accumulation but not with NAFLD or other cardiometabolic traits or diseases. Although the absolute effect sizes of GFATadj on LDL cholesterol were more pronounced in women compared to men, most associations did not differ by sex. CONCLUSIONS: The inability of subcutaneous fat depots to efficiently store energy substrates could be the causal factor underlying the association of visceral lipid deposition with cardiometabolic health.


Assuntos
Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Feminino , Gordura Intra-Abdominal/diagnóstico por imagem , Gordura Intra-Abdominal/patologia , Diabetes Mellitus Tipo 2/patologia , Análise da Randomização Mendeliana , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/genética , Doenças Cardiovasculares/patologia , Colesterol
2.
Mol Metab ; 74: 101763, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37364709

RESUMO

OBJECTIVE: Glucocorticoid (GC) excess contributes to the development of metabolic syndrome, defined by visceral obesity, abnormal glucose tolerance, and dyslipidemia. While it is accepted that loss of metabolic control is causative of cutaneous diseases, the systemic effects of epidermal dysfunction have received limited attention. Importantly, independent of GC blood levels, skin synthesis of these hormones can provide tissue-specific variations that may affect global homeostasis. We aimed to assess whether the epidermal-specific loss of the GC receptor (GR) had an impact on the dermal white adipose tissue (dWAT), a specialized fat depot functionally different from other fat pads, as well as on whole body homeostasis. METHODS: GR epidermal KO (GREKO) and control female mice were treated with oral corticosterone (CORT) for 4 weeks, a protocol inducing metabolic dysfunction. Metabolic parameters including body weight, visceral and hepatic fat accumulation, blood glucose and insulin levels, glucose tolerance tests upon fasting, and triglycerides levels, were determined. Systemic alterations of soluble factors with known roles in immunity and inflammation were also assessed by a multiplex antibody array system containing selected cytokines, chemokines, and growth factors. The levels of cutaneous GCs and the profile of skin-secreted factors were determined in tissue explants by ELISA and the multiplex array system. Morphometric studies quantitated changes in dWAT thickness and adipocyte size in both genotypes, basally and at the end of CORT treatment. The expression of adipocyte markers was assessed in purified dermal adipocytes in vehicle and CORT-treated GREKOvs controls. RESULTS: Despite similar circulating levels of GCs, GREKO mice were highly resistant to CORT-induced systemic metabolic anomalies including body weight gain, visceral and hepatic fat, hyperglycemia, insulinemia, and elevated levels of plasma triglycerides, leptin, FGF-21, PAI-1, and CCL11. GREKO mice featured constitutively enhanced levels of cutaneous GCs relative to controls at least partially due to keratinocyte-specific increased expression of the critical steroidogenic enzyme Cyp11b1. Also, the higher ratio of skin-secreted protective vs inflammatory adipokines in GREKOvs controls, correlated with higher capacity of adipogenic conversion in experiments using conditioned media from tissue explants. Following CORT treatment, relative to controls, GREKO mice featured reduced dWAT hyperplasia and adipocyte hypertrophy, with increased Adipoq and decreased Lipocalin 2 expression in purified dermal adipocytes. CONCLUSIONS: Overall data suggest that epidermal GR loss results in paracrine actions on dermal adipocytes as well as endocrine actions on key metabolic tissues that significantly improve the whole body metabolism in a mouse model of metabolic dysfunction.


Assuntos
Corticosterona , Receptores de Glucocorticoides , Feminino , Animais , Camundongos , Corticosterona/metabolismo , Receptores de Glucocorticoides/metabolismo , Tecido Adiposo/metabolismo , Glucocorticoides/metabolismo , Peso Corporal , Triglicerídeos/metabolismo
4.
Int J Mol Sci ; 24(8)2023 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-37108673

RESUMO

Recently, substantial attention has been paid toward adipose-derived mesenchymal stem cells (AdMSCs) as a potential therapy in tissue engineering and regenerative medicine applications. Rat AdMSCs (r-AdMSCs) are frequently utilized. However, the influence of the adipose depot site on the multilineage differentiation potential of the r-AdMSCs is still ambiguous. Hence, the main objective of this study was to explore the influence of the adipose tissue harvesting location on the ability of r-AdMSCs to express the stem-cell-related markers and pluripotency genes, as well as their differentiation capacity, for the first time. Herein, we have isolated r-AdMSCs from the inguinal, epididymal, peri-renal, and back subcutaneous fats. Cells were compared in terms of their phenotype, immunophenotype, and expression of pluripotency genes using RT-PCR. Additionally, we investigated their potential for multilineage (adipogenic, osteogenic, and chondrogenic) induction using special stains confirmed by the expression of the related genes using RT-qPCR. All cells could positively express stem cell marker CD 90 and CD 105 with no significant in-between differences. However, they did not express the hematopoietic markers as CD 34 and CD 45. All cells could be induced successfully. However, epididymal and inguinal cells presented the highest capacity for adipogenic and osteogenic differentiation (21.36-fold and 11.63-fold for OPN, 29.69-fold and 26.68-fold for BMP2, and 37.67-fold and 22.35-fold for BSP, respectively, in epididymal and inguinal cells (p < 0.0001)). On the contrary, the subcutaneous cells exhibited a superior potential for chondrogenesis over the other sites (8.9-fold for CHM1 and 5.93-fold for ACAN, (p < 0.0001)). In conclusion, the adipose tissue harvesting site could influence the differentiation capacity of the isolated AdMSCs. To enhance the results of their employment in various regenerative cell-based therapies, it is thus vital to take the collection site selection into consideration.


Assuntos
Células-Tronco Mesenquimais , Osteogênese , Ratos , Masculino , Animais , Tecido Adiposo/metabolismo , Células-Tronco Mesenquimais/metabolismo , Gordura Subcutânea , Diferenciação Celular , Células Cultivadas
5.
Int J Mol Sci ; 24(7)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37047284

RESUMO

Body mass index (BMI) and blood biomarkers are not enough to predict cardiovascular disease risk. Apolipoprotein B was identified to be associated with cardiovascular disease (CVD) progression. The Dual-energy X-ray Absorption (DXA) results could be considered as a predictor for cardiovascular disease in a more refined way based on fat distribution. The prediction of CVD risk by simple indicators still cannot meet clinical needs. The association of ApoB with specific fat depot features remains to be explored to better co-predict cardiovascular disease risk. An amount of 5997 adults from National Health and Nutrition Examination Survey (NHANES) were enrolled. Their demographic information, baseline clinical condition, blood examination, and DXA physical examination data were collected. Multivariate regression was used to assess the correlation between ApoB and site-specific fat characteristics through different adjusted models. Smooth curve fittings and threshold analysis were used to discover the turning points with 95% confidence intervals. ApoB is positively correlated with arms percent fat, legs percent fat, trunk percent fat, android percent fat, gynoid percent fat, arm circumference and waist circumference after adjustment with covariates for age, gender, race, hypertension, diabetes, hyperlipidemia, coronary heart disease, smoking status and vigorous work activity. The smooth curve fitting and threshold analysis also showed that depot-specific fat had lower turning points of ApoB in both males and females within the normal reference range of ApoB. Meanwhile, females have a lower increase in ApoB per 1% total percent fat and android percent fat than males before the turning points, while females have a higher growth of ApoB per 1% gynoid percent fat than males. The combined specific fat-depot DXA and ApoB analysis could indicate the risk of CVD in advance of lipid biomarkers or DXA alone.


Assuntos
Doenças Cardiovasculares , Obesidade , Masculino , Feminino , Adulto , Humanos , Inquéritos Nutricionais , Doenças Cardiovasculares/etiologia , Absorciometria de Fóton , Índice de Massa Corporal , Apolipoproteínas B
6.
J Dairy Sci ; 106(2): 807-821, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36460514

RESUMO

The purpose of this article is to review body condition scoring and the role of body fat reserves in relation to insulin sensitivity and metabolic phenotyping. This article summarizes body condition scoring assessment methods and the differences between subcutaneous and visceral fat depots in dairy cows. The mass of subcutaneous and visceral adipose tissue (AT) changes significantly during the transition period; however, metabolism and intensity of lipolysis differ between subcutaneous and visceral AT depots of dairy cows. The majority of studies on AT have focused on subcutaneous AT, and few have explored visceral AT using noninvasive methods. In this systematic review, we summarize the relationship between body fat reserves and insulin sensitivity and integrate omics research (e.g., metabolomics, proteomics, lipidomics) for metabolic phenotyping of cows, particularly overconditioned cows. Several studies have shown that AT insulin resistance develops during the prepartum period, especially in overconditioned cows. We discuss the role of AT lipolysis, fatty acid oxidation, mitochondrial function, acylcarnitines, and lipid insulin antagonists, including ceramide and glycerophospholipids, in cows with different body condition scoring. Nonoptimal body conditions (under- or overconditioned cows) exhibit marked abnormalities in metabolic and endocrine function. Overall, reducing the number of cows with nonoptimal body conditions in herds seems to be the most practical solution to improve profitability, and dairy farmers should adjust their management practices accordingly.


Assuntos
Doenças dos Bovinos , Resistência à Insulina , Feminino , Bovinos , Animais , Insulina/metabolismo , Lactação , Tecido Adiposo/metabolismo , Lipólise , Dieta/veterinária , Doenças dos Bovinos/metabolismo
7.
BMC Med ; 20(1): 317, 2022 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-36117169

RESUMO

BACKGROUND: Obesity is a well-established risk factor for atrial fibrillation (AF). Whether body fat depots differentially associate with AF development remains unknown. METHODS: In the prospective population-based Rotterdam Study, body composition was assessed using dual-energy X-ray absorptiometry (DXA) and liver and epicardial fat using computed tomography (CT). A body composition score was constructed by adding tertile scores of each fat depot. Principal component analysis was conducted to identify potential body fat distribution patterns. Cox proportional hazards regression was used to calculate hazard ratios and 95% confidence intervals (HR; 95% CI) per 1-standard deviation increase in corresponding fat depots to enable comparisons. RESULTS: Over a median follow-up of 9.6 and 8.6 years, 395 (11.4%) and 172 (8.0%) AF cases were ascertained in the DXA and the CT analyses, respectively. After adjustments for cardiovascular risk factors, absolute fat mass (HR; 95% CI 1.33; 1.05-1.68), gynoid fat mass (HR; 95% CI 1.36; 1.12-1.65), epicardial fat mass (HR; 95% CI 1.27; 1.09-1.48), and android-to-gynoid fat ratio (HR; 95% CI 0.81; 0.70-0.94) were independently associated with new-onset AF. After further adjustment for lean mass, associations between fat mass (HR; 95% CI 1.17; 1.04-1.32), gynoid fat mass (HR; 95% CI 1.21; 1.08-1.37), and android-to-gynoid fat ratio (HR; 95% CI 0.84; 0.72-0.97) remained statistically significant. Larger body fat score was associated with a higher AF risk (HR; 95% CI 1.10; 1.02-1.20). Borderline significant association was found between a subcutaneous fat predominant pattern with AF onset (HR; 95% CI 1.21; 0.98-1.49). CONCLUSIONS: Various body fat depots were associated with new-onset AF. Total fat mass and gynoid fat mass were independently associated with AF after adjustment for body size. The inverse association between android-to-gynoid fat ratio with AF presents a novel finding. A significant dose-response relationship between body fat accumulation and AF was observed. Our results underscore the predominant role of subcutaneous fat on AF development among a middle-aged and elderly population. Associations betw2een body fat depots, fat distribution and new-onset atrial fibrillation. ABBREVIATIONS: AF, atrial fibrillation.


Assuntos
Fibrilação Atrial , Tecido Adiposo/diagnóstico por imagem , Idoso , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/epidemiologia , Composição Corporal , Distribuição da Gordura Corporal , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos
8.
J Hepatol ; 77(6): 1504-1514, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35988689

RESUMO

BACKGROUND & AIMS: Adipose tissue dysfunction is involved in the development of insulin resistance and is responsible for excessive lipid delivery to other organs such as the liver. We tested the hypothesis that impaired mitochondrial function is a common feature of subcutaneous (SAT) and visceral adipose tissue (VAT), but may differently contribute to adipose tissue insulin resistance (IR) in obesity, non-alcoholic fatty liver (NAFL) and steatohepatitis (NASH). METHODS: In this cross-sectional study, we analyzed tissue-specific insulin sensitivity using stable isotope dilution and hyperinsulinemic-normoglycemic clamp tests. We also assessed mitochondrial respiration, mRNA and protein expression, and tissue morphology in biopsies of SAT and VAT from obese humans without NAFL, with NAFL or with NASH (n = 22/group). RESULTS: Compared to individuals without liver disease, persons with NAFL and NASH had about 30% (p = 0.010) and 33% (p = 0.002) lower maximal mitochondrial respiration, respectively, in VAT, but not in SAT. The lower maximal mitochondrial respiration of VAT was associated with lower adipose tissue insulin sensitivity (ß = 0.985, p = 0.041) and with increased VAT protein expression of tumor necrosis factor A across all groups (ß = -0.085, p = 0.040). VAT from individuals with NASH was characterized by lower expression of oxidative phosphorylation complex IV (p = 0.042) and higher mRNA expression of the macrophage marker CD68 (p = 0.002) than VAT from participants without NAFL. CONCLUSIONS: Humans with non-alcoholic fatty liver disease have distinct abnormalities of VAT energy metabolism, which correlate with adipose tissue dysfunction and may favor progression of NAFL to NASH. LAY SUMMARY: Adipose tissue (commonly called body fat) can be found under the skin (subcutaneous) or around internal organs (visceral). Dysfunction of adipose tissue can cause insulin resistance and lead to excess delivery of fat to other organs such as the liver. Herein, we show that dysfunction specifically in visceral adipose tissue was associated with fatty liver disease. CLINICAL TRIAL NUMBER: NCT01477957.


Assuntos
Resistência à Insulina , Hepatopatia Gordurosa não Alcoólica , Humanos , Estudos Transversais , Obesidade/complicações , Respiração , Tecido Adiposo , Mitocôndrias , RNA Mensageiro
9.
Horm Mol Biol Clin Investig ; 43(4): 449-453, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-35796296

RESUMO

BACKGROUND: Vaspin is an adipocytokine with insulin-sensitizing and anti-inflammatory traits. OBJECTIVES: The purpose of this study was to evaluate the effect of high-intensity interval training (HIIT) on serum, visceral and subcutaneous adipose tissue vaspin levels in rats exposed to a diet high in fat and sugar (HFS). MATERIALS AND METHODS: Thirty-two male Wistar rats were randomly divided into HFS and standard diet (SD) groups. After 12 weeks, each group was divided into sedentary and HIIT groups. HIIT program was performed 3 times/week for 8 weeks. Retroperitoneal adipose tissue, inguinal adipose tissue and serum were collected to analyze vaspin levels. Also, serum glucose and insulin levels, insulin resistance index (HOMA-IR) and retroperitoneal and inguinal fat weights were measured. RESULTS: HFS significantly increased weight gain, weight of inguinal (p=0.001) and retroperitoneal fat depots (p<0.001), serum glucose levels (p<0.001) and HOMA-IR (p<0.001). The HIIT was able to decline weight gain and fat mass (p<0.05) but did not affect inguinal and retroperitoneal fat depots' vaspin levels. Eight weeks' HIIT significantly increased serum vaspin (p=0.002) and decreased insulin (p=0.001) levels only in rats fed with SD. CONCLUSIONS: Although the HIIT program can cause significantly reducing effects on weight gain and fat depots' weights, it does not effect on circulating and fat depots' vaspin levels in rats fed an HFS.


Assuntos
Treinamento Intervalado de Alta Intensidade , Resistência à Insulina , Ratos , Masculino , Animais , Sacarose , Ratos Wistar , Tecido Adiposo , Insulina , Dieta Hiperlipídica/efeitos adversos , Aumento de Peso , Glucose
10.
Life (Basel) ; 12(4)2022 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-35454985

RESUMO

We investigated associations between intakes of human milk (HM) components (macronutrients and biologically active molecules) and regional fat depots development in healthy term infants (n = 20) across the first year of lactation. Infant limb (mid-arm and mid-thigh) lean and fat areas were assessed by ultrasound imaging at 2, 5, 9 and 12 months of age. Concentrations of HM total protein, whey protein, casein, adiponectin, leptin, lysozyme, lactoferrin, secretory IGA, total carbohydrates, lactose, HM oligosaccharides (total HMO, calculated) and infant 24-h milk intake were measured, and infant calculated daily intakes (CDI) of HM components were determined. This pilot study shows higher 24-h milk intake was associated with a larger mid-arm fat area (p = 0.024), higher breastfeeding frequency was associated with larger mid-arm (p = 0.008) and mid-thigh (p < 0.001) fat areas. Lysozyme (p = 0.001) and HMO CDI (p = 0.004) were time-dependently associated with the mid-arm fat area. Intakes of HM components and breastfeeding parameters may modulate infant limb fat depots development during the first year of age and potentially promote favorable developmental programming of infant body composition; however, further studies are needed to confirm these findings.

11.
Tomography ; 8(2): 560-569, 2022 02 27.
Artigo em Inglês | MEDLINE | ID: mdl-35314623

RESUMO

Background: Specification of adipose tissues by whole-body magnetic resonance imaging (MRI) was performed and related to pulmonary function parameters in a population-based cohort. Methods: 203 study participants underwent whole-body MRI and pulmonary function tests as part of the KORA (Cooperative Health Research in the Augsburg Region) MRI study. Both visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were derived from the T1-Dixon sequence, and hepatic adipose tissue from the proton density fat fraction (PDFFhepatic). Associations between adipose tissue parameters and spirometric indices such as forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and Tiffeneau-index (FEV1/FVC) were examined using multivariate linear regression analysis excluding cofounding effects of other clinical parameters. Results: VAT (ß = −0.13, p = 0.03) and SAT (ß = −0.26, p < 0.001), but not PDFFhepatic were inversely associated with FEV1, while VAT (ß = −0.27, p < 0.001), SAT (ß = −0.41, p < 0.001), and PDFFhepatic (ß = −0.17, p = 0.002) were inversely associated with FVC. PDFFhepatic was directly associated with the Tiffeneau index (ß = 2.46, p < 0.001). Conclusions: In the adjusted linear regression model, VAT was inversely associated with all measured spirometric parameters, while PDFFhepatic revealed the strongest association with the Tiffeneau index. Non-invasive adipose tissue quantification measurements might serve as novel biomarkers for respiratory impairment.


Assuntos
Imageamento por Ressonância Magnética , Imagem Corporal Total , Tecido Adiposo/diagnóstico por imagem , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Gordura Subcutânea
12.
Biology (Basel) ; 11(2)2022 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-35205177

RESUMO

Adipogenesis, through adipocyte hyperplasia and/or hypertrophy, leads to increased adiposity, giving rise to obesity. A genome-wide transcriptome analysis of in vitro adipogenesis in human adipose-derived stromal/stem cells identified SLC7A8 (Solute Carrier Family 7 Member 8) as a potential novel mediator. The current study has investigated the role of SLC7A8 in adipose tissue biology using a mouse model of diet-induced obesity. slc7a8 knockout (KO) and wildtype (WT) C57BL/6J mice were fed either a control diet (CD) or a high-fat diet (HFD) for 14 weeks. On the HFD, both WT and KO mice (WTHFD and KOHFD) gained significantly more weight than their CD counterparts. However, KOHFD gained significantly less weight than WTHFD. KOHFD had significantly reduced levels of glucose intolerance compared with those observed in WTHFD. KOHFD also had significantly reduced adipocyte mass and hypertrophy in inguinal, mesenteric, perigonadal, and brown adipose depots, with a corresponding decrease in macrophage infiltration. Additionally, KOHFD had decreased lipid accumulation in the liver, heart, gastrocnemius muscle, lung, and kidney. This study demonstrates that targeting slc7a8 protects against diet-induced obesity by reducing lipid accumulation in multiple organs and suggests that if targeted, has the potential to mitigate the development of obesity-associated comorbidities.

13.
Cell Metab ; 34(3): 458-472.e6, 2022 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-35021043

RESUMO

In mammals, white adipose tissues are largely divided into visceral epididymal adipose tissue (EAT) and subcutaneous inguinal adipose tissue (IAT) with distinct metabolic properties. Although emerging evidence suggests that subpopulations of adipose stem cells (ASCs) would be important to explain fat depot differences, ASCs of two fat depots have not been comparatively investigated. Here, we characterized heterogeneous ASCs and examined the effects of intrinsic and tissue micro-environmental factors on distinct ASC features. We demonstrated that ASC subpopulations in EAT and IAT exhibited different molecular features with three adipogenic stages. ASC transplantation experiments revealed that intrinsic ASC features primarily determined their adipogenic potential. Upon obesogenic stimuli, EAT-specific SDC1+ ASCs promoted fibrotic remodeling, whereas IAT-specific CXCL14+ ASCs suppressed macrophage infiltration. Moreover, IAT-specific BST2high ASCs exhibited a high potential to become beige adipocytes. Collectively, our data broaden the understanding of ASCs with new insights into the origin of white fat depot differences.


Assuntos
Adipócitos , Tecido Adiposo , Adipócitos/metabolismo , Adipogenia , Tecido Adiposo/metabolismo , Animais , Mamíferos , Células-Tronco/metabolismo , Gordura Subcutânea/metabolismo
14.
Cells ; 10(6)2021 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-34208471

RESUMO

TBC1D4 (AS160) and TBC1D1 are Rab GTPase-activating proteins that play a key role in the regulation of glucose and possibly the transport of long chain fatty acids (LCFAs) into muscle and fat cells. Knockdown (KD) of TBC1D4 increased CD36/SR-B2 and FABPpm protein expressions in L6 myotubes, whereas in murine cardiomyocytes, TBC1D4 deficiency led to a redistribution of CD36/SR-B2 to the sarcolemma. In our study, we investigated the previously unexplored role of both Rab-GAPs in LCFAs uptake in human adipocytes differentiated from the ADMSCs of subcutaneous and visceral adipose tissue origin. To this end we performed a single- and double-knockdown of the proteins (TBC1D1 and TBC1D4). Herein, we provide evidence that AS160 mediates fatty acid entry into the adipocytes derived from ADMSCs. TBC1D4 KD resulted in quite a few alterations to the cellular phenotype, the most obvious of which was the shift of the CD36/SR-B2 transport protein to the plasma membrane. The above translated into an increased uptake of saturated long-chain fatty acid. Interestingly, we observed a tissue-specific pattern, with more pronounced changes present in the adipocytes derived from subADMSCs. Altogether, our data show that in human adipocytes, TBC1D4, but not TBC1D1, deficiency increases LCFAs transport via CD36/SR-B2 translocation.


Assuntos
Adipócitos/metabolismo , Ácidos Graxos/metabolismo , Proteínas Ativadoras de GTPase/deficiência , Gordura Intra-Abdominal/metabolismo , Gordura Subcutânea/metabolismo , Antígenos CD36/metabolismo , Células Cultivadas , Feminino , Humanos , Proteínas de Membrana Lisossomal/metabolismo , Células-Tronco Mesenquimais/metabolismo , Pessoa de Meia-Idade , Receptores Depuradores/metabolismo
15.
Exp Cell Res ; 406(1): 112740, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-34303697

RESUMO

Body fat depots are heterogeneous concerning their embryonic origin, structure, exposure to environmental stressors, and availability. Thus, investigating adipose-derived mesenchymal stromal cells (ASCs) from different sources is essential to standardization for future therapies. In vitro amplification is also critical because it may predispose cell senescence and mutations, reducing regenerative properties and safety. Here, we evaluated long-term culture of human facial ASCs (fASCs) and abdominal ASCs (aASCs) and showed that both met the criteria for MSCs characterization but presented differences in their immunophenotypic profile, and differentiation and clonogenic potentials. The abdominal tissue yielded more ASCs, and these had higher proliferative potential, but facial cells displayed fewer mitotic errors at higher passages. However, both cell types reduced clonal efficiency over time and entered replicative senescence around P12, as evaluated by progressive morphological alterations, reduced proliferative capacity, and SA-ß-galactosidase expression. Loss of genetic integrity was detected by a higher proportion of cells showing nuclear alterations and γ-H2AX expression. Our findings indicate that the source of ASCs can substantially influence their phenotype and therefore should be carefully considered in future cell therapies, avoiding, however, long-term culture to ensure genetic stability.


Assuntos
Adipócitos/metabolismo , Tecido Adiposo/metabolismo , Linhagem da Célula/genética , Condrócitos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Osteócitos/metabolismo , Abdome , Adipócitos/citologia , Tecido Adiposo/citologia , Adulto , Biomarcadores/metabolismo , Diferenciação Celular , Proliferação de Células , Senescência Celular , Condrócitos/citologia , Células Clonais , Face , Feminino , Expressão Gênica , Histonas/genética , Histonas/metabolismo , Humanos , Células-Tronco Mesenquimais/citologia , Pessoa de Meia-Idade , Mitose , Especificidade de Órgãos , Osteócitos/citologia , Fenótipo , Cultura Primária de Células , beta-Galactosidase/genética , beta-Galactosidase/metabolismo
16.
Animals (Basel) ; 11(5)2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-34069824

RESUMO

This work aimed to compare pre- and post-slaughter methodologies to estimate body fat reserves in dairy goats. Twenty-six lactating Saanen goats ranging from 43.6 to 69.4 kg of body weight (BW) and from 1.84 to 2.96 of body condition score (BCS; 0-5 range) were used. Fifteen pre-slaughter and four post-slaughter measurement values were used to estimate the weight of fat in the omental (OM), mesenteric (MES), perirenal (PR), organ (ORG), carcass (CARC), and non-carcass components (NC) and total (TOT, calculated as the sum of CARC and NC) depots in goats. The pre-slaughter measurements were withers height; rump height; rump length; pelvis width; chest depth; shoulder width; heart girth; body length; sternum height; BW; BCS assessed in the lumbar (BCSl) and sternal (BCSs) regions; and fat thickness measured by ultrasound in the lumbar (FTUSl), sternal (FTUSs), and perirenal (FTUSpr) regions. The post-slaughter measurements were hot carcass weight (HCW), empty body weight (EBW), and fat thickness measured by digital caliper in the lumbar (FTDCl) and sternal (FTDCs) regions. Linear and multiple regressions were fit to data collected. BW, BCS (from lumbar and sternal regions), all somatic measurements, and fat thickness measured by ultrasound in the lumbar and sternal regions were not adequate to estimate the weight of total fat in lactating Saanen goats (R2 ≤ 0.55). The best pre-slaughter and post-slaughter estimators of OM, MES, PR, ORG, NC, and TOT fat were FTUSpr and EBW, respectively. Among pre- and post-slaughter measurements, BCSl (R2 = 0.63) and HCW (R2 = 0.82) provided the most accurate predictions of CARC fat, respectively. Multiple regression using the pre-slaughter variables FTUSpr, BW, and BCSl yielded estimates of TOT fat with an R2 = 0.92 (RSD = 1.14 kg). On the other hand, TOT fat predicted using the post-slaughter variables HCW and FTDCs had an R2 = 0.83 (RSD = 1.41 kg). These results confirm that fat reserves can be predicted in lactating Saanen goats with high precision using multiple regression equations combining in vivo measurements.

17.
Adipocyte ; 10(1): 119-123, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-33591224

RESUMO

Adipose tissue blood flow (ATBF) is an important determinant of adipose tissue (AT) function. 133Xenon wash-out technique is considered the gold-standard for human ATBF measurements. However, decreasing 133Xenon clinical use and costly production and preservation, make alternative (non-invasive) methods necessary. Here, we explored percutaneous Doppler ultrasound as a proxy method to quantify intravascular subcutaneous abdominal and femoral ATBF in humans (n= 17). Both fasting ATBF and the postprandial increase in ATBF were significantly higher in abdominal compared to femoral AT. Although anatomical variations in vein location and depot thickness may impact feasibility, we demonstrate that Doppler ultrasound detects the expected depot-differences and postprandial increase in ATBF in healthy individuals. This method warrants further investigation in other populations and metabolic conditions.


Assuntos
Tecido Adiposo/irrigação sanguínea , Tecido Adiposo/diagnóstico por imagem , Circulação Sanguínea/fisiologia , Adulto , Jejum/fisiologia , Feminino , Fêmur/diagnóstico por imagem , Humanos , Gordura Intra-Abdominal/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Obesidade/metabolismo , Período Pós-Prandial/fisiologia , Ultrassonografia Doppler/métodos , Ultrassonografia de Intervenção/métodos
18.
Transl Anim Sci ; 4(4): txaa179, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33196015

RESUMO

Relationships between live body condition score (BCS) and carcass fat depots have not been well established in equine. Our study was designed to quantify the relationship between BCS and fat depot measurements from equine carcasses. Live horses (n = 429) were evaluated immediately prior to immobilization at a commercial equine processor. Horses were independently assigned a BCS by a panel of three trained evaluators; BCS was evaluated by visual appraisal and manual palpation of the neck, withers, back, ribs, behind the shoulder, and tailhead. Median BCS frequencies were: 3.0 (n = 9), 4.0 (n = 43), 5.0 (n = 116), 6.0 (n = 86), 7.0 (n = 72), 8.0 (n = 76), and 9.0 (n = 27). Sex (stallion [n = 5], mare [n = 159], or gelding [n = 114]) and breed type (draft [n = 56], stock [n = 363], pony [n = 8], or mule [n =3]) were also denoted. Horses were processed for human consumption according to industry-accepted procedures under the supervision of the Canadian Food Inspection Agency. During the harvest process, all kidney-pelvic-heart (KPH) fat was trimmed from the carcass and weighed. After chilling, the marbling score was subjectively evaluated using beef grading standards. Carcass fat trim was weighed during the fabrication process. As BCS increased, hot carcass weight (HCW), absolute KPH weight, KPH expressed as a percentage of HCW, marbling score, neck fat depth, absolute weight of trimmed carcass fat, and trimmed carcass fat as a percentage of HCW increased (P < 0.01). A strong correlation (r = 0.74; P < 0.01) was detected between BCS and absolute KPH weight. Similarly, correlations between BCS and percentage of KPH (r = 0.65), neck fat depth (r = 0.60), absolute trimmed carcass fat (r = 0.58), trimmed carcass fat as a percentage of HCW (r = 0.54), marbling score (r = 0.54), and HCW (r = 0.52) were also detected (P < 0.01). These data indicate a strong relationship between subjective live BCS and objectively measured carcass fat depots in various equine breed types and sexes.

19.
Res Vet Sci ; 133: 180-187, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32992129

RESUMO

The present study established multiple linear regression models using two ultrasound in vivo measurements (at lumbar and sternal regions, with different real-time ultrasonography machines and probes) and live weight, to predict simultaneously carcass composition and body fat depots of different breeds of sheep and goat. This study is important for the small ruminant industry, considering the feasibility of using the ultrasound methodology in field conditions, as well as an online system of the carcass evaluation. The multiple linear regression models were obtained by selecting the best subset of variables between using the in vivo measurements (raw variables), their second degree and interactions, evaluated in terms of prediction performance using cross-validation "K-folds" and validated by a test group. Overall, high accuracy (adj R2) was obtained from the linear relationship between predicted and experimental values of the group test for each of the nine dependent variables, with values varying between adj R2 0.88 and 0.98.


Assuntos
Tecido Adiposo , Criação de Animais Domésticos/métodos , Composição Corporal , Peso Corporal , Cabras/anatomia & histologia , Ovinos/anatomia & histologia , Ultrassonografia/veterinária , Criação de Animais Domésticos/instrumentação , Animais , Cruzamento , Modelos Lineares , Masculino , Análise Multivariada , Reprodutibilidade dos Testes , Ultrassonografia/instrumentação , Ultrassonografia/normas
20.
BMC Genomics ; 21(1): 77, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992204

RESUMO

BACKGROUND: This study used a genome-wide screen of gene expression to better understand the metabolic and functional differences between commercially valuable intramuscular fat (IMF) and commercially wasteful subcutaneous (SC) fat depots in Bos taurus beef cattle. RESULTS: We confirmed many findings previously made at the biochemical level and made new discoveries. The fundamental lipogenic machinery, such as ACACA and FASN encoding the rate limiting Acetyl CoA carboxylase and Fatty Acid synthase were expressed at 1.6-1.8 fold lower levels in IMF, consistent with previous findings. The FA elongation pathway including the rate limiting ELOVL6 was also coordinately downregulated in IMF compared to SC as expected. A 2-fold lower expression in IMF of ACSS2 encoding Acetyl Coenzyme A synthetase is consistent with utilisation of less acetate for lipogenesis in IMF compared to SC as previously determined using radioisotope incorporation. Reduced saturation of fat in the SC depot is reflected by 2.4 fold higher expression of the SCD gene encoding the Δ9 desaturase enzyme. Surprisingly, CH25H encoding the cholesterol 25 hydroxylase enzyme was ~ 36 fold upregulated in IMF compared to SC. Moreover, its expression in whole muscle tissue appears representative of the proportional representation of bovine marbling adipocytes. This suite of observations prompted quantification of a set of oxysterols (oxidised forms of cholesterol) in the plasma of 8 cattle exhibiting varying IMF. Using Liquid Chromatography-Mass Spectrometry (LC-MS) we found the levels of several oxysterols were significantly associated with multiple marbling measurements across the musculature, but (with just one exception) no other carcass phenotypes. CONCLUSIONS: These data build on our molecular understanding of ruminant fat depot biology and suggest oxysterols represent a promising circulating biomarker for cattle marbling.


Assuntos
Adipócitos/metabolismo , Expressão Gênica , Metaboloma , Músculo Esquelético , Gordura Subcutânea/citologia , Transcriptoma , Adipogenia/genética , Animais , Bovinos , Análise por Conglomerados , Biologia Computacional/métodos , Metabolismo Energético , Perfilação da Expressão Gênica/métodos , Metabolômica/métodos , Músculo Esquelético/citologia , Especificidade de Órgãos/genética
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