scholarly journals Site-Specific Reduction of Oxidative and Lipid Metabolism in Adipose Tissue of 3′-Azido-3′-Deoxythymidine-Treated Rats

2006 ◽  
Vol 51 (2) ◽  
pp. 583-590 ◽  
Author(s):  
Catherine Deveaud ◽  
Bertrand Beauvoit ◽  
Annabel Reynaud ◽  
Jacques Bonnet

ABSTRACT Although it is well accepted that treatment with some nucleoside reverse transcriptase inhibitors modifies both fat metabolism and fat distribution in humans, the mechanisms underlying these modifications are not yet known. The present investigation examined whether a decrease in oxidative capacity, induced by a chronic oral administration of 3′-azido-3′-deoxythymidine (AZT) in rats, could be associated with an alteration of the lipogenic capacity of white adipose tissues. The impact of obesity as a factor was then evaluated. Results showed that AZT treatment induced differential effects depending on anatomical localization. Indeed, in the inguinal adipose tissue, the specific activities of cytochrome c oxidase and fatty acid synthase, two rate-controlling enzymes in energy and lipogenic metabolisms, respectively, both decreased under AZT treatment, thus leading to a lowered cell lipid accumulation. Moreover, the AMP-activated protein kinase phosphorylation level tended to increase, thus implying that AZT causes an energy imbalance. Furthermore, the inguinal tissue of obese rats presented a sensitivity to AZT treatment that was higher than that of lean rats. In contrast, for epididymal tissue, no significant change in all these parameters could be detected under AZT treatment, regardless of the nutritional status of the animals. Taken together, these data demonstrate differential effects of AZT on subcutaneous adipose tissue and visceral white adipose tissue. It could be considered that the chronic decreases in energy and lipogenic metabolism of inguinal adipocyte, consecutive to AZT treatment, may lead, in the long term, to adipose tissue atrophy.

Author(s):  
Teruhide Koyama ◽  
Nagato Kuriyama ◽  
Ritei Uehara

Background: The aim of this study was to investigate whether plasma midregional proadrenomedullin (MR-proADM) reflected body composition, such as body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), VAT/SAT ratio, body fat mass (BFM), and skeletal muscle mass (SMM). Methods: A total of 2244 individuals (727 men and 1517 women) were included in the study. Multiple regression analysis was performed to assess the combined influence of variables: age, daily alcohol consumption, Brinkman index, sleeping time, metabolic equivalents, anamnesis for hypertension, dyslipidemia, diabetes, and body composition of MR-proADM, by using a stepwise forward selection method. Results: MR-proADM was significantly related to all anthropometric indices (BMI, VAT, SAT, VAT/SAT ratio, BFM, and SMM) in men and women. On the basis of a stepwise forward selection method, VAT (men: beta = 0.184, p < 0.001, women: beta = 0.203, p < 0.001) and BFM (beta = 0.181, p < 0.001) in women, were found to be significantly associated with MR-proADM. Conclusion: This study suggests that plasma MR-proADM concentration is a more reliable indicator of VAT for fat distribution, and thus, MR-proADM may help better understand the obesity paradox. Changes in circulating levels of MR-proADM could possibly reflect changes in body composition, endocrine, and metabolic milieu.


2018 ◽  
Vol 124 (3) ◽  
pp. 729-740 ◽  
Author(s):  
Lærke Bertholdt ◽  
Anders Gudiksen ◽  
Tomasz Stankiewicz ◽  
Ida Villesen ◽  
Jonas Tybirk ◽  
...  

Recruitment of fatty acids from adipose tissue is increased during fasting. However, the molecular mechanisms behind fasting-induced metabolic regulation in human adipose tissue and the potential impact of training state in this are unknown. Therefore the aim of the present study was to investigate 1) fasting-induced regulation of lipolysis and glyceroneogenesis in human adipose tissue as well as 2) the impact of training state on basal oxidative capacity and fasting-induced metabolic regulation in human adipose tissue. Untrained [maximal oxygen uptake (V̇o2max) < 45 ml·min−1·kg−1] and trained subjects (V̇o2max > 55 ml·min−1·kg−1) fasted for 36 h, and abdominal subcutaneous adipose tissue biopsies were obtained 2, 12, 24, and 36 h after a standardized meal. Adipose tissue oxidative phosphorylation complexes, phosphoenolpyruvate carboxykinase, and pyruvate dehydrogenase (PDH)-E1α protein as well as PDH kinase (PDK) 2, PDK4, and PDH phosphatase 2 mRNA content were higher in trained subjects than in untrained subjects. In addition, trained subjects had higher adipose tissue hormone-sensitive lipase Ser660 phosphorylation and adipose triglyceride lipase protein content as well as higher plasma free fatty acid concentration than untrained subjects during fasting. Moreover, adipose tissue PDH phosphorylation increased with fasting only in trained subjects. Taken together, trained subjects seem to possess higher basal adipose tissue oxidative capacity as well as higher capacity for regulation of lipolysis and for providing substrate for glyceroneogenesis in adipose tissue during fasting than untrained subjects. NEW & NOTEWORTHY This study shows for the first time higher protein content of lipolytic enzymes and higher oxidative phosphorylation protein in adipose tissue from trained subjects than from untrained subjects during fasting. Furthermore, trained subjects had higher capacity for adipose tissue glyceroneogenesis than untrained subjects.


Author(s):  
Felicitas Lanzl ◽  
Fabian Duddeck ◽  
Saskia Willuweit ◽  
Steffen Peldschus

Abstract A deeper understanding of the mechanical characteristics of adipose tissue under large deformation is important for the analysis of blunt force trauma, as adipose tissue alters the stresses and strains that are transferred to subjacent tissues. Hence, results from drop tower tests of subcutaneous adipose tissue are presented (i) to characterise adipose tissue behaviour up to irreversible deformation, (ii) to relate this to the microstructural configuration, (iii) to quantify this deformation and (iv) to provide an analytical basis for computational modelling of adipose tissue under blunt impact. The drop tower experiments are performed exemplarily on porcine subcutaneous adipose tissue specimens for three different impact velocities and two impactor geometries. An approach based on photogrammetry is used to derive 3D representations of the deformation patterns directly after the impact. Median values for maximum impactor acceleration for tests with a flat cylindrical impactor geometry at impact velocities of 886 mm/s, 1253 mm/s and 2426 mm/s amount to 61.1 g, 121.6 g and 264.2 g, respectively, whereas thickness reduction of the specimens after impact amount to 16.7%, 30.5% and 39.3%, respectively. The according values for tests with a spherically shaped impactor at an impact velocity of 1253 mm/s are 184.2 g and 78.7%. Based on these results, it is hypothesised that, in the initial phase of a blunt impact, adipose tissue behaviour is mainly governed by the behaviour of the lipid inside the adipocytes, whereas for further loading, contribution of the extracellular collagen fibre network becomes more dominant.


2019 ◽  
Author(s):  
John F. Dou ◽  
Muraly Puttabyatappa ◽  
Vasantha Padmanabhan ◽  
Kelly M. Bakulski

AbstractBackgroundBisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood.ObjectiveTo determine the impact of prenatal BPA exposure on the transcriptome of VAT and SAT adipose depots.MethodsRNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Differences in transcriptional profiling of SAT and VAT in controls and the effect of prenatal BPA treatment on individual genes and gene pathways were determined.ResultsThere were 179 differentially expressed genes (padjusted<0.05, log2-fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways.ConclusionPrenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.


2010 ◽  
Vol 299 (2) ◽  
pp. E258-E265 ◽  
Author(s):  
Katrien Koppo ◽  
Dominique Larrouy ◽  
Marie A. Marques ◽  
Michel Berlan ◽  
Magda Bajzova ◽  
...  

The aim of this study was to evaluate the relative contributions of various hormones involved in the regulation of lipid mobilization in subcutaneous adipose tissue (SCAT) during exercise and to assess the impact of obesity on this regulation. Eight lean and eight obese men performed a 60-min cycle exercise bout at 50% of their peak oxygen uptake on two occasions: during intravenous infusion of octreotide (a somatostatin analog) or physiological saline (control condition). Lipolysis in SCAT was evaluated using in situ microdialysis. One microdialysis probe was perfused with the adrenergic blockers phentolamine and propranolol while another probe was perfused with the phosphodiesterase and adenosine receptor inhibitor aminophylline. Compared with the control condition, infusion of octreotide reduced plasma insulin levels in lean (from ∼3.5 to 0.5 μU/ml) and in obese (from ∼9 to 2 μU/ml), blunted the exercise-induced rise in plasma GH and epinephrine levels in both groups, and enhanced the exercise-induced natriuretic peptide (NP) levels in lean but not in obese subjects. In both groups, octreotide infusion resulted in higher exercise-induced increases in dialysate glycerol concentrations in the phentolamine-containing probe while no difference in lipolytic response was found in the aminophylline-containing probe. The results suggest that insulin antilipolytic action plays a role in the regulation of lipolysis during exercise in lean as well as in obese subjects. The octreotide-induced enhancement of exercise lipolysis in lean subjects was associated with an increased exercise-induced plasma NP response. Adenosine may contribute to the inhibition of basal lipolysis in both subject groups.


2011 ◽  
Vol 36 (10) ◽  
pp. 1360-1365 ◽  
Author(s):  
Z Kovacova ◽  
M Tencerova ◽  
B Roussel ◽  
Z Wedellova ◽  
L Rossmeislova ◽  
...  

2005 ◽  
Vol 288 (4) ◽  
pp. E741-E747 ◽  
Author(s):  
Tongjian You ◽  
Rongze Yang ◽  
Mary F. Lyles ◽  
Dawei Gong ◽  
Barbara J. Nicklas

Adipose tissue is a major source of inflammatory and thrombotic cytokines. This study investigated the relationship of abdominal subcutaneous adipose tissue cytokine gene expression to body composition, fat distribution, and metabolic risk during obesity. We determined body composition, abdominal fat distribution, plasma lipids, and abdominal subcutaneous fat gene expression of leptin, TNF-α, IL-6, PAI-1, and adiponectin in 20 obese, middle-aged women (BMI, 32.7 ± 0.8 kg/m2; age, 57 ± 1 yr). A subset of these women without diabetes ( n = 15) also underwent an OGTT. In all women, visceral fat volume was negatively related to leptin ( r = −0.46, P < 0.05) and tended to be negatively related to adiponectin ( r = −0.38, P = 0.09) gene expression. Among the nondiabetic women, fasting insulin ( r = 0.69, P < 0.01), 2-h insulin ( r = 0.56, P < 0.05), and HOMA index ( r = 0.59, P < 0.05) correlated positively with TNF-α gene expression; fasting insulin ( r = 0.54, P < 0.05) was positively related to, and 2-h insulin ( r = 0.49, P = 0.06) tended to be positively related to, IL-6 gene expression; and glucose area ( r = −0.56, P < 0.05) was negatively related to, and insulin area ( r = −0.49, P = 0.06) tended to be negatively related to, adiponectin gene expression. Also, adiponectin gene expression was significantly lower in women with vs. without the metabolic syndrome (adiponectin-β-actin ratio, 2.26 ± 0.46 vs. 3.31 ± 0.33, P < 0.05). We conclude that abdominal subcutaneous adipose tissue expression of inflammatory cytokines is a potential mechanism linking obesity with its metabolic comorbidities.


2018 ◽  
Author(s):  
Craig A. Glastonbury ◽  
Alexessander Couto Alves ◽  
Julia S. El-Sayed Moustafa ◽  
Kerrin S. Small

AbstractAdipose tissue is comprised of a heterogeneous collection of cell-types which can differentially impact disease phenotypes. We investigated cell-type heterogeneity in two population-level subcutaneous adipose tissue RNAseq datasets (TwinsUK, N =766 and GTEx, N=326). We find that adipose cell-type composition is heritable and confirm the positive association between macrophage proportion and obesity (BMI), but find a stronger BMI-independent association with DXA-derived body-fat distribution traits. Cellular heterogeneity can confound ‘omic analyses, but is rarely taken into account in analysis of solid-tissue transcriptomes. We benchmark the impact of adipose tissue cell-composition on a range of standard analyses, including phenotypegene expression association, co-expression networks and cis-eQTL discovery. We applied G x Cell Type Proportion interaction models to identify 26 cell-type specific eQTLs in 20 genes, including 4 autoimmune disease GWAS loci, demonstrating the potential of in silico deconvolution of bulk tissue to identify cell-type restricted regulatory variants.


2021 ◽  
Author(s):  
Veronica Mocanu ◽  
Daniel V. Timofte ◽  
Ioana Hristov

Adipocyte expansion, which involves adipose tissue-derived mesenchymal stem cells (ASCs), is a critical process with implications in the pathogenesis of metabolic syndrome and insulin resistance associated with obesity. Impaired subcutaneous adipogenesis leads to dysfunctional, hypertrophic adipocytes, chronic low-grade inflammation, and peripheric insulin resistance. Alternatively, it has also been proposed that the preservation of the functionality of subcutaneous adipocyte precursors could contribute to some obese individuals remaining metabolically healthy. Very few studies evaluated the changes in the adipogenic differentiation for human subcutaneous ASCs following bariatric surgery. Weight loss after bariatric surgery involves extensive remodeling of adipose tissue, comprising the hyperplasia-hypertrophy balance. Subcutaneous ASCs may be implicated in the variations of bariatric outcomes, through a different restoration in their proliferative and adipogenic potential. Weight loss induced by bariatric surgery correlates to the subcutaneous ASC functions and could explain the variability of metabolic improvement. Limited research data are available to the present and these data support the importance of diagnosis of subcutaneous ASCs functions as predictors of metabolic improvement after bariatric surgery.


Sign in / Sign up

Export Citation Format

Share Document