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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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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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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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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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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.
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Does Fatty Acid Composition in Subcutaneous Adipose Tissue Differ between Patients with Alzheimer's Disease and Cohabiting Proxies?
Faxen-Irving, G, Falahati, F, Basun, H, Eriksdotter, M, Vedin, I, Wahlund, LO, Schultzberg, M, Hjorth, E, Palmblad, J, Cederholm, T, et al
Journal of Alzheimer's disease : JAD. 2018;(2):515-519
Abstract
Low tissue levels of the major marine ω3 fatty acids (FAs) DHA and EPA are found in Alzheimer's disease (AD). We investigated if healthy proxies to AD patients have higher levels of these ω3 FAs. We observed lower levels of EPA and DHA in subcutaneous adipose tissue biopsies from 64 AD patients compared with 16 cognitively healthy proxies. No significant difference was observed when pairwise comparisons were made between a subset of 16 AD patients and their co-habiting proxies. Larger studies are needed to replicate these findings and to determine if they could depend on FA intake or differences in metabolism.
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Randomized trial evaluating the effect of aged garlic extract with supplements versus placebo on adipose tissue surrogates for coronary atherosclerosis progression.
Zeb, I, Ahmadi, N, Flores, F, Budoff, MJ
Coronary artery disease. 2018;(4):325-328
Abstract
AIMS: Increased epicardial adipose tissue (EAT), pericardial adipose tissue (PAT), periaortic adipose tissue (PaAT), and subcutaneous adipose tissue (SAT) are mediators of metabolic risk, and are associated with the severity of coronary artery calcium (CAC). Aged garlic extract (AGE) has been shown to reduce the progression of coronary atherosclerosis. This study evaluates the effect of AGE with supplements (AGE+S) on EAT, PAT, SAT, and PaAT. METHODS Sixty asymptomatic participants participated in a randomized trial evaluating the effect of AGE+S versus placebo on coronary atherosclerosis progression, and underwent CAC at baseline and after 12 months of treatment. EAT, PAT, PaAT, and SAT volumes were measured on CAC scans. PAT was calculated as: intrathoracic adipose tissue-EAT. SAT was defined as the volume of fat depot anterior to the sternum and posterior to the vertebra. PaAT was defined as fat depot around the descending aorta. RESULTS At 1 year, the increase in EAT, PAT, PaAT, and SAT was significantly lower in the AGE+S as compared with the placebo group (P<0.05). The odds ratios of increase in EAT, PAT, PaAT, and SAT were 0.63 [95% confidence interval (CI): 0.43-0.90], 0.72 (95% CI: 0.45-0.93), 0.81 (95% CI: 0.65-0.98), and 0.87 (CI: 0.52-0.98), respectively, compared with the placebo group, which even remained significant (all P<0.05) after adjustment for cardiovascular risk factors and statin therapy and BMI. CONCLUSION This study shows that AGE+S is associated with favorable effects on reducing the progression rate of adipose tissue volumes.
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Effect of Dietary Carbohydrate Type on Serum Cardiometabolic Risk Indicators and Adipose Tissue Inflammatory Markers.
Meng, H, Matthan, NR, Fried, SK, Berciano, S, Walker, ME, Galluccio, JM, Lichtenstein, AH
The Journal of clinical endocrinology and metabolism. 2018;(9):3430-3438
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CONTEXT AND OBJECTIVE Direct comparisons between types of dietary carbohydrate in terms of cardiometabolic risk indicators are limited. This study was designed to compare the effects of an isocaloric exchange of simple, refined, and unrefined carbohydrates on serum cardiometabolic risk indicators, adipose tissue inflammatory markers, and peripheral blood mononuclear cell (PBMC) fractional cholesterol efflux. DESIGN, PARTICIPANTS, AND MEASURES Participants [postmenopausal women and men (N = 11), 65 ± 8 years, body mass index 29.8 ± 3.2 kg/m2, low-density lipoprotein (LDL) cholesterol ≥2.6 mmol/L] were provided with diets (60% energy from total carbohydrate, 15% from protein, 25% from fat) for 4.5 weeks in a randomized crossover design, with 2-week washout periods. The variable component was an isocaloric exchange of simple, refined, or unrefined carbohydrate-containing foods. Serum lipoprotein, glucose, insulin, and inflammatory marker concentrations were measured. Abdominal subcutaneous adipose tissue was aspirated to assess macrophage and inflammatory marker gene expression and ex vivo cytokine secretion, and PBMCs were isolated to assess ex vivo fractional cholesterol efflux. RESULTS Fasting serum LDL and non-high-density lipoprotein (HDL) cholesterol concentrations were higher after the refined compared with simple or unrefined carbohydrate-enriched diets (P < 0.01). Other serum measures, ex vivo fractional cholesterol efflux and adipose tissue gene expression and ex vivo cytokine secretion, were similar between diets. CONCLUSIONS Diets enriched in refined compared with simple or unrefined carbohydrate resulted in higher fasting serum LDL and non-HDL cholesterol concentrations but had little effect on other cardiometabolic risk indicators. This small study raises the intriguing possibility that refined carbohydrate may have unique adverse effects on cardiometabolic risk indicators distinct from simple and unrefined carbohydrate.
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Six-month Calorie Restriction in Overweight Individuals Elicits Transcriptomic Response in Subcutaneous Adipose Tissue That is Distinct From Effects of Energy Deficit.
Lam, YY, Ghosh, S, Civitarese, AE, Ravussin, E
The journals of gerontology. Series A, Biological sciences and medical sciences. 2016;(10):1258-65
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Abstract
Calorie restriction confers health benefits distinct from energy deficit by exercise. We characterized the adipose-transcriptome to investigate the molecular basis of the differential phenotypic responses. Abdominal subcutaneous fat was collected from 24 overweight participants randomized in three groups (N = 8/group): weight maintenance (control), 25% energy deficit by calorie restriction alone (CR), and 25% energy deficit by calorie restriction with structured exercise (CREX). Within each group, gene expression was compared between 6 months and baseline with cutoffs at nominal p ≤ .01 and absolute fold-change ≥ 1.5. Gene-set enrichment analysis (false discovery rate < 5%) was used to identify significantly regulated biological pathways. CR and CREX elicited similar overall clinical response to energy deficit and a comparable reduction in gene transcription specific to oxidative phosphorylation and proteasome function. CR vastly outweighed CREX in the number of differentially regulated genes (88 vs 39) and pathways (28 vs 6). CR specifically downregulated the chemokine signaling-related pathways. Among the CR-regulated genes, 27 functioned as transcription/translation regulators (eg, mRNA processing or transcription/translation initiation), whereas CREX regulated only one gene in this category. Our data suggest that CR has a broader effect on the transcriptome compared with CREX which may mediate its specific impact on delaying primary aging.