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1.
Ultrasound evaluation of subcutaneous and visceral abdominal fat as a predictor of gestational diabetes mellitus: a systematic review.
Benevides, FT, Araujo Júnior, E, Maia, CSC, Montenegro Junior, RM, Carvalho, FHC
The journal of maternal-fetal & neonatal medicine : the official journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians. 2022;(11):2216-2226
Abstract
OBJECTIVE Studies of subcutaneous and visceral abdominal fat thickness evaluated by ultrasound as a predictor of gestational diabetes mellitus (GDM) have been published, but the best technique and standardization are unknown. To identify, critically evaluate, and analyze studies using subcutaneous and visceral abdominal fat as a model for predicting GDM in the first and second trimesters of pregnancy and evaluate their methodological quality. METHODS PubMed, Scopus, and Web of Science databases were searched from May to July 2019. We included studies of any sample size performed for any duration and in any configuration. Model development and validation studies were eligible for inclusion. Two authors independently performed the eligibility assessment of the studies by reviewing the titles and abstracts. Data on study design, gestational age, diagnostic criteria for GDM, device, ultrasound fat measurement technique, and cutoff point for GDM prediction were extracted. RESULTS The electronic search resulted in 1331 articles, of which 14 were eligible for systematic review. Different criteria for diagnosing GDM and fat measurement techniques were used. The cutoff point for subcutaneous, visceral, and total abdominal fat for predicting GDM in the first and second trimesters varied between the studies. CONCLUSION No study validated the model for predicting GDM using subcutaneous and visceral abdominal fat measurements. External validation studies are recommended to improve the generalization of this GDM predictor in clinical practice.
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2.
Taurine supplementation in conjunction with exercise modulated cytokines and improved subcutaneous white adipose tissue plasticity in obese women.
De Carvalho, FG, Brandao, CFC, Muñoz, VR, Batitucci, G, Tavares, MEA, Teixeira, GR, Pauli, JR, De Moura, LP, Ropelle, ER, Cintra, DE, et al
Amino acids. 2021;(9):1391-1403
Abstract
Interventions that can modulate subcutaneous white adipose tissue (scWAT) function, such as exercise training and nutritional components, like taurine, modulate the inflammatory process, therefore, may represent strategies for obesity treatment. We investigated the effects of taurine supplementation in conjunction with exercise on inflammatory and oxidative stress markers in plasma and scWAT of obese women. Sixteen obese women were randomized into two groups: Taurine supplementation group (Tau, n = 8) and Taurine supplementation + exercise group (Tau + Exe, n = 8). The intervention was composed of daily taurine supplementation (3 g) and exercise training for 8 weeks. Anthropometry, body fat composition, and markers of inflammatory and oxidative stress were determined in plasma and scWAT biopsy samples before and after the intervention. We found that, although taurine supplementation increased taurine plasma levels, no changes were observed for the anthropometric characteristics. However, Tau alone decreased interleukin-6 (IL-6), and in conjunction with exercise (Tau + Exe), increased anti-inflammatory interleukins (IL-15 and IL10), followed by reduced IL1β gene expression in the scWAT of obese women. Tau and Tau + Exe groups presented reduced adipocyte size and increased connective tissue and multilocular droplets. In conclusion, taurine supplementation in conjunction with exercise modulated levels of inflammatory markers in plasma and scWAT, and improved scWAT plasticity in obese women, promoting protection against obesity-induced inflammation. TRN NCT04279600 retrospectively registered on August 18, 2019.
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3.
Association between Subcutaneous Adipose Tissue Inflammation, Insulin Resistance, and Calorie Restriction in Obese Females.
Sbierski-Kind, J, Mai, K, Kath, J, Jurisch, A, Streitz, M, Kuchenbecker, L, Babel, N, Nienen, M, Jürchott, K, Spranger, L, et al
Journal of immunology (Baltimore, Md. : 1950). 2020;(1):45-55
Abstract
The worldwide epidemic of overweight and obesity has led to an increase in associated metabolic comorbidities. Obesity induces chronic low-grade inflammation in white adipose tissue (WAT). However, the function and regulation of both innate and adaptive immune cells in human WAT under conditions of obesity and calorie restriction (CR) is not fully understood yet. Using a randomized interventional design, we investigated postmenopausal overweight or obese female subjects who either underwent CR for 3 mo followed by a 4-wk phase of weight maintenance or had to maintain a stable weight over the whole study period. A comprehensive immune phenotyping protocol was conducted using validated multiparameter flow cytometry analysis in blood and s.c. WAT (SAT). The TCR repertoire was analyzed by next-generation sequencing and cytokine levels were determined in SAT. Metabolic parameters were determined by hyperinsulinemic-euglycemic clamp. We found that insulin resistance correlates significantly with a shift toward the memory T cell compartment in SAT. TCR analysis revealed a diverse repertoire in SAT of overweight or obese individuals. Additionally, whereas weight loss improved systemic insulin sensitivity in the intervention group, SAT displayed no significant improvement of inflammatory parameters (cytokine levels and leukocyte subpopulations) compared with the control group. Our data demonstrate the accumulation of effector memory T cells in obese SAT and an association between systemic glucose homeostasis and inflammatory parameters in obese females. The long-standing effect of obesity-induced changes in SAT was demonstrated by preserved immune cell composition after short-term CR-induced weight loss.
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4.
Vertebral Bone Marrow Fat Is independently Associated to VAT but Not to SAT: KORA FF4-Whole-Body MR Imaging in a Population-Based Cohort.
Hasic, D, Lorbeer, R, Bertheau, RC, Machann, J, Rospleszcz, S, Nattenmüller, J, Rathmann, W, Peters, A, Bamberg, F, Schlett, CL
Nutrients. 2020;(5)
Abstract
The objective of the current study was to assess the relationship of bone marrow adipose tissue (BMAT) content to abdominal fat depots, including visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT), as well as cardiovascular risk factors (CVRF) beyond physical activity in a population-based cohort study undergoing whole-body magnetic resonance (MR) imaging. Subjects of the Cooperative Health Research in the Augsburg Region (KORA) FF4 study without known cardiovascular disease underwent fat fraction quantification in vertebrae (BMATL1/L2) via a 2-point T1-weighted volumetric interpolated breath-hold examination (VIBE) Dixon sequence. The same MR sequence was applied to quantify VAT and SAT volume. Subjects' characteristics, including physical activity, were determined through standardized exams and self-assessment questionnaires. Univariate and multivariate linear regression were applied. In the cohort of 378 subjects (56 ± 9.1years; 42.1% female), BMATL1/L2 was 54.3 ± 10.1%, VAT was 4.54 ± 2.71 L, and SAT was 8.10 ± 3.68 L. VAT differed significantly across BMATL1/L2 tertiles (3.60 ± 2.76 vs. 4.92 ± 2.66 vs. 5.11 ± 2.48; p < 0.001), there was no significant differences for SAT (p = 0.39). In the fully adjusted model, VAT remained positively associated with BMATL1/L2 (β = 0.53, p = 0.03). Furthermore, BMATL1/L2 was associated with age (β = 5.40 per 10-years, p < 0.001), hemoglobin A1c (HbA1c; β = 1.55 per 1%, p = 0.04), lipids (β = 0.20 per 10 mg/dL triglycerides; β = 0.40 per 10 mg/dL low-density lipoprotein (LDL); β =-3.21 lipid-lowering medication; all p < 0.05), and less physical activity (β = 3.7 "no or nearly no exercise" as compared to "≥2 h per week, regularly", p = 0.003); gender was not significantly different (p = 0.57). In the population-based cohort, VAT but not SAT were associated with higher BMATL1/L2 independently of physical activity and other cardiovascular risk factors. Further, BMATL1/L2 increased with older age, less physical activity, higher HbA1c, and increased lipids but decreased with lipid-lowering medication.
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Acute effects of active breaks during prolonged sitting on subcutaneous adipose tissue gene expression: an ancillary analysis of a randomised controlled trial.
Grace, MS, Formosa, MF, Bozaoglu, K, Bergouignan, A, Brozynska, M, Carey, AL, Veiga, CB, Sethi, P, Dillon, F, Bertovic, DA, et al
Scientific reports. 2019;(1):3847
Abstract
Active breaks in prolonged sitting has beneficial impacts on cardiometabolic risk biomarkers. The molecular mechanisms include regulation of skeletal muscle gene and protein expression controlling metabolic, inflammatory and cell development pathways. An active communication network exists between adipose and muscle tissue, but the effect of active breaks in prolonged sitting on adipose tissue have not been investigated. This study characterized the acute transcriptional events induced in adipose tissue by regular active breaks during prolonged sitting. We studied 8 overweight/obese adults participating in an acute randomized three-intervention crossover trial. Interventions were performed in the postprandial state and included: (i) prolonged uninterrupted sitting; or prolonged sitting interrupted with 2-minute bouts of (ii) light- or (iii) moderate-intensity treadmill walking every 20 minutes. Subcutaneous adipose tissue biopsies were obtained after each condition. Microarrays identified 36 differentially expressed genes between the three conditions (fold change ≥0.5 in either direction; p < 0.05). Pathway analysis indicated that breaking up of prolonged sitting led to differential regulation of adipose tissue metabolic networks and inflammatory pathways, increased insulin signaling, modulation of adipocyte cell cycle, and facilitated cross-talk between adipose tissue and other organs. This study provides preliminary insight into the adipose tissue regulatory systems that may contribute to the physiological effects of interrupting prolonged sitting.
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Plasma and tissue pharmacokinetics of fosfomycin in morbidly obese and non-obese surgical patients: a controlled clinical trial.
Dorn, C, Petroff, D, Neumann, N, Kratzer, A, El-Najjar, N, Dietrich, A, Kloft, C, Zeitlinger, M, Kees, MG, Kees, F, et al
The Journal of antimicrobial chemotherapy. 2019;(8):2335-2340
Abstract
OBJECTIVES To assess the pharmacokinetics and tissue penetration of fosfomycin in obese and non-obese surgical patients. METHODS Fifteen obese patients undergoing bariatric surgery and 15 non-obese patients undergoing major intra-abdominal surgery received an intravenous single short infusion of 8 g of fosfomycin. Fosfomycin concentrations were determined by LC-MS/MS in plasma and microdialysate from subcutaneous tissue up to 8 h after dosing. The pharmacokinetic analysis was performed in plasma and interstitial fluid (ISF) by non-compartmental methods. RESULTS Thirteen obese patients (BMI 38-50 kg/m2) and 14 non-obese patients (BMI 0-29 kg/m2) were evaluable. The pharmacokinetics of fosfomycin in obese versus non-obese patients were characterized by lower peak plasma concentrations (468 ± 139 versus 594 ± 149 mg/L, P = 0.040) and higher V (24.4 ± 6.4 versus 19.0 ± 3.1 L, P = 0.010). The differences in AUC∞ were not significant (1275 ± 477 versus 1515 ± 352 mg·h/L, P = 0.16). The peak concentrations in subcutaneous tissue were reached rapidly and declined in parallel with the plasma concentrations. The drug exposure in tissue was nearly halved in obese compared with non-obese patients (AUC∞ 1052 ± 394 versus 1929 ± 725 mg·h/L, P = 0.0010). The tissue/plasma ratio (AUCISF/AUCplasma) was 0.86 ± 0.32 versus 1.27 ± 0.34 (P = 0.0047). CONCLUSIONS Whereas the pharmacokinetics of fosfomycin in plasma of surgical patients were only marginally different between obese and non-obese patients, the drug exposure in subcutaneous tissue was significantly lower in the obese patients.
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Subcutaneous Adipose Tissue and Systemic Inflammation Are Associated With Peripheral but Not Hepatic Insulin Resistance in Humans.
van der Kolk, BW, Kalafati, M, Adriaens, M, van Greevenbroek, MMJ, Vogelzangs, N, Saris, WHM, Astrup, A, Valsesia, A, Langin, D, van der Kallen, CJH, et al
Diabetes. 2019;(12):2247-2258
Abstract
Obesity-related insulin resistance (IR) may develop in multiple organs, representing various etiologies for cardiometabolic diseases. We identified abdominal subcutaneous adipose tissue (ScAT) transcriptome profiles in liver or muscle IR by means of RNA sequencing in overweight or obese participants of the Diet, Obesity, and Genes (DiOGenes) (NCT00390637, ClinicalTrials.gov) cohort (n = 368). Tissue-specific IR phenotypes were derived from a 5-point oral glucose tolerance test. Hepatic and muscle IR were characterized by distinct abdominal ScAT transcriptome profiles. Genes related to extracellular remodeling were upregulated in individuals with primarily hepatic IR, while genes related to inflammation were upregulated in individuals with primarily muscle IR. In line with this, in two independent cohorts, the Cohort on Diabetes and Atherosclerosis Maastricht (CODAM) (n = 325) and the Maastricht Study (n = 685), an increased systemic low-grade inflammation profile was specifically related to muscle IR but not to liver IR. We propose that increased ScAT inflammatory gene expression may translate into an increased systemic inflammatory profile, linking ScAT inflammation to the muscle IR phenotype. These distinct IR phenotypes may provide leads for more personalized prevention of cardiometabolic diseases.
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Modulation of Human Subcutaneous Adipose Tissue MicroRNA Profile Associated with Changes in Adiposity-Related Parameters.
Giardina, S, Hernández-Alonso, P, Salas-Salvadó, J, Rabassa-Soler, A, Bulló, M
Molecular nutrition & food research. 2018;(2)
Abstract
SCOPE To analyze the effect of three calorie-restricted diets with different amount and quality of carbohydrates on subcutaneous adipose tissue (SAT) microRNA (miRNA) profile. METHODS AND RESULTS 6-month parallel, randomized trial conducted on overweight and obese subjects randomized to: 1) low glycemic index diet (LGI), 2) high glycemic index diet (HGI), and 3) low-fat (LF). The genome-wide SAT miRNA profile was assessed in eight randomly selected participants and the most relevant changing miRNAs (n = 13) were validated in 48 subjects. None of the miRNAs showed significant changes between the intervention groups. However, changes in some of them correlated with changes in biochemical and anthropometric variables. Stratifying our population according to tertiles of percentage change in body weight (BW), we observed a significant down-regulation of miR-210 in those subjects in Tertile 1 as compared to Tertile 3. When our population was stratified by tertiles of waist circumference, miR-132, miR-29a, miR-34a, and miR-378 were found to be significantly down-regulated, in T2 compared to T3. Furthermore, when stratified by tertiles of fat mass, we also observed the significant down-regulation of miR-132 in T1. CONCLUSION The macronutrient composition of a calorie-restricted diet does not affect the expression of the miRNAs analyzed, while changes in adiposity play a primary regulatory role.
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Aging Modulates the Influence of Arginase on Endothelial Dysfunction in Obesity.
Masi, S, Colucci, R, Duranti, E, Nannipieri, M, Anselmino, M, Ippolito, C, Tirotta, E, Georgiopoulos, G, Garelli, F, Nericcio, A, et al
Arteriosclerosis, thrombosis, and vascular biology. 2018;(10):2474-2483
Abstract
Objective- Arginase can reduce NO availability. In this study, we explored arginase as a determinant of endothelial dysfunction in small arteries from obese patients and its relationship with aging and microvascular remodeling. Approach and Results- Small arteries were dissected after subcutaneous fat biopsies and evaluated on a pressurized micromyograph. Endothelium-dependent vasodilation was assessed by acetylcholine, repeated under L-NAME ( N G-nitro-L-arginine-methyl ester), N(ω)-hydroxy-nor-l-arginine (arginase inhibitor) and gp91ds-tat (NADPH [nicotinamide adenine dinucleotide phosphate oxidase] oxidase inhibitor) in vessels from young (age <30 years) control and obese and old (>30 years) control and obese subjects. Media-lumen ratio and amount of vascular wall fibrosis were used as markers of vascular remodeling. Amount of vascular superoxide anions and NO production were determined with immunofluorescence, whereas arginase expression was quantified using Western blot and quantitative polymerase chain reaction. Obese and older age groups had lower vascular NO, as well as higher media-lumen ratio, wall fibrosis, intravascular superoxide, and blunted inhibitory effect of L-NAME on acetylcholine versus controls and younger age groups. N(ω)-hydroxy-nor-l-arginine restored the acetylcholine-induced vasodilation in young and, to a lesser extent, in old obese subjects. This effect was abolished by addition of L-NAME. Gp91ds-tat increased the vasodilatory response to N(ω)-hydroxy-nor-l-arginine in old obese. Superoxide anions and arginase I/II levels were higher in the vascular wall of obese versus controls. Conclusions- Arginase contributes to microvascular endothelial dysfunction in obesity. Its impact is reduced by aging because of higher levels of vascular oxidative stress. Obesity is accompanied by accelerated microvascular remodeling, the extent of which is related to the amount of arginase in the vascular wall.
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Decreased lipogenesis-promoting factors in adipose tissue in postmenopausal women with overweight on a Paleolithic-type diet.
Blomquist, C, Chorell, E, Ryberg, M, Mellberg, C, Worrsjö, E, Makoveichuk, E, Larsson, C, Lindahl, B, Olivecrona, G, Olsson, T
European journal of nutrition. 2018;(8):2877-2886
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Abstract
PURPOSE We studied effects of diet-induced postmenopausal weight loss on gene expression and activity of proteins involved in lipogenesis and lipolysis in adipose tissue. METHODS Fifty-eight postmenopausal women with overweight (BMI 32.5 ± 5.5) were randomized to eat an ad libitum Paleolithic-type diet (PD) aiming for a high intake of protein and unsaturated fatty acids or a prudent control diet (CD) for 24 months. Anthropometry, plasma adipokines, gene expression of proteins involved in fat metabolism in subcutaneous adipose tissue (SAT) and lipoprotein lipase (LPL) activity and mass in SAT were measured at baseline and after 6 months. LPL mass and activity were also measured after 24 months. RESULTS The PD led to improved insulin sensitivity (P < 0.01) and decreased circulating triglycerides (P < 0.001), lipogenesis-related factors, including LPL mRNA (P < 0.05), mass (P < 0.01), and activity (P < 0.001); as well as gene expressions of CD36 (P < 0.05), fatty acid synthase, FAS (P < 0.001) and diglyceride acyltransferase 2, DGAT2 (P < 0.001). The LPL activity (P < 0.05) and gene expression of DGAT2 (P < 0.05) and FAS (P < 0.05) were significantly lowered in the PD group versus the CD group at 6 months and the LPL activity (P < 0.05) remained significantly lowered in the PD group compared to the CD group at 24 months. CONCLUSIONS Compared to the CD, the PD led to a more pronounced reduction of lipogenesis-promoting factors in SAT among postmenopausal women with overweight. This could have mediated the favorable metabolic effects of the PD on triglyceride levels and insulin sensitivity.