scholarly journals Peripheral Blood Mononuclear Cell Metabolism Acutely Adapted to Postprandial Transition and Mainly Reflected Metabolic Adipose Tissue Adaptations to a High-Fat Diet in Minipigs

Nutrients ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 1816 ◽  
Author(s):  
Yuchun Zeng ◽  
Jérémie David ◽  
Didier Rémond ◽  
Dominique Dardevet ◽  
Isabelle Savary-Auzeloux ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Peripheral Blood ◽  
Time Course ◽  
Mononuclear Cells ◽  
Cell Metabolism ◽  
Whole Body ◽  
High Fat ◽  
Short Term ◽  
Peripheral Blood Mononuclear ◽  
First Time

Although peripheral blood mononuclear cells (PBMCs) are widely used as a valuable tool able to provide biomarkers of health and diseases, little is known about PBMC functional (biochemistry-based) metabolism, particularly following short-term nutritional challenges. In the present study, the metabolic capacity of minipig PBMCs to respond to nutritional challenges was explored at the biochemical and molecular levels. The changes observed in enzyme activities following a control test meal revealed that PBMC metabolism is highly reactive to the arrival of nutrients and hormones in the circulation. The consumption, for the first time, of a high fat–high sucrose (HFHS) meal delayed or sharply reduced most of the observed postprandial metabolic features. In a second experiment, minipigs were subjected to two-month HFHS feeding. The time-course follow-up of metabolic changes in PBMCs showed that most of the adaptations to the new diet took place during the first week. By comparing metabolic (biochemical and molecular) PMBC profiles to those of the liver, skeletal muscle, and adipose tissue, we concluded that although PBMCs conserved common features with all of them, their response to the HFHS diet was closely related to that of the adipose tissue. As a whole, our results show that PBMC metabolism, particularly during short-term (postprandial) challenges, could be used to evaluate the whole-body metabolic status of an individual. This could be particularly interesting for early diagnosis of metabolic disease installation, when fasting clinical analyses fail to diagnose the path towards the pathology.

scholarly journals Effect of high-fat diet on peripheral blood mononuclear cells and adipose tissue in early stages of diet-induced weight gain

2019 ◽  
Vol 122 (12) ◽  
pp. 1359-1367 ◽  
Author(s):  
Jake E. Lowry ◽  
Batbayar Tumurbaatar ◽  
Claudia D’Agostino ◽  
Erika Main ◽  
Traver J. Wright ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Peripheral Blood ◽  
High Fat Diet ◽  
Time Course ◽  
Mononuclear Cells ◽  
High Fat ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells ◽  
Inflammatory Changes

AbstractSubcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.

scholarly journals Effects of cold exposure revealed by global transcriptomic analysis in ferret peripheral blood mononuclear cells

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Bàrbara Reynés ◽  
Evert M. van Schothorst ◽  
Jaap Keijer ◽  
Andreu Palou ◽  
Paula Oliver
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Peripheral Blood Mononuclear Cells ◽  
Cold Exposure ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Cell Cycle Gene ◽  
Peripheral Blood Mononuclear ◽  
Brown Adipose ◽  
Blood Mononuclear Cells

AbstractAnimal studies, mostly performed in rodents, show the beneficial anti-obesity effects of cold studies. This is due to thermogenic activation of brown adipose tissue (BAT), a tissue also recently discovered in adult humans. Studies in humans, however, are hampered by the accessibility of most tissues. In contrast, peripheral blood mononuclear cells (PBMC) are accessible and share the expression profile of different sets of genes with other tissues, including those that reflect metabolic responses. Ferrets are an animal model physiologically closer to humans than rodents. Here, we investigated the effects on ferrets of one-week acclimation to 4 °C by analysing the PBMC transcriptome. Cold exposure deeply affected PBMC gene expression, producing a widespread down-regulation of genes involved in different biological pathways (cell cycle, gene expression regulation/protein synthesis, immune response, signal transduction, and genes related to extracellular matrix/cytoskeleton), while thermogenic and glycogenolysis-related processes were increased. Results obtained in PBMC reflected those of adipose tissue, but hardly those of the liver. Our study, using ferret as a model, reinforce PBMC usefulness as sentinel biological material for cold-exposure studies in order to deepen our understanding of the general and specific pathways affected by cold acclimation. This is relevant for future development of therapies to be used clinically.

CD4+ T-cell immunity predicts long-lasting antitumor immunity after PD-1 blockade therapy.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2545-2545
Author(s):  
Kyoichi Kaira ◽  
Ou Yamaguchi ◽  
Kenichi Yoshimura ◽  
Atsuto Mouri ◽  
Ayako Shiono ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Mononuclear Cells ◽  
Therapy Response ◽  
T Cell Immunity ◽  
Prediction Formula ◽  
Short Term ◽  
Peripheral Blood Mononuclear ◽  
Cell Immunity

2545 Background: Patients treated with programmed cell death 1 (PD-1)-blockade therapy fall into 3 distinct subgroups: non-responders presenting early disease progression, long survivors who achieve durable disease control, and the remaining short-term responders. We reported that the prediction formula comprised of the percentages of CD62L-downregulated (CD62Llow) and CD25+FOXP3+CD4+T cells in the peripheral blood predicted non-responders of non-small cell lung cancer patients (n = 50) scheduled to receive anti-PD-1-antibody (nivolumab) therapy in the 2017 ASCO meeting. In this study, we included 171 patients with NSCLC who were scheduled for nivolumab treatment after obtaining written informed consent. Peripheral blood mononuclear cells (PBMC) were examined before and after Nivolumab therapy up to 2 years to investigate the differences between long survivors and short-term responders. Methods: The patients received Nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks. Tumor response was assessed with the use of the Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1, at week 8 and every 8 weeks thereafter. PBMCs were analyzed with a 18-color microfluorometer, LSR Fortessa and a masscytometer, CyTOF. Results: The responder-type patient group whose prediction formula values were greater than 192 showed significantly longer PFS ( P< 0.0001) and OS ( P< 0.0001). The long survivors who consisted of tail plateau of PFS exhibited significantly more CD62LlowCD4+T cells than the short-term responders as pre-existing immunity. The remaining responders kept significantly higher percentages of CD62LlowCD4+T cells ( P= 0.0088) and prediction formula values ( P= 0.017) than the patients with acquired resistance. Conclusions: The pre-existing CD4+T cell balance between primed effector and regulatory T cells correlated with anti-PD-1 therapy response. Further, CD62Llowcell-dominant CD4+T cell immunity was required to maintain durable antitumor reactivity induced by anti-PD-1 antibody therapy. These results have important clinical implication, as they support anti-PD-1 therapy provision to all potentially responding patients and pave the way for new treatment strategies for patients with distinct CD4+T cell immune statuses. Clinical trial information: UMIN000020719.

scholarly journals Interscapular and Perivascular Brown Adipose Tissue Respond Differently to a Short-Term High-Fat Diet

2019 ◽  
Author(s):  
Peter Aldiss ◽  
Jo Lewis ◽  
David Boocock ◽  
Amanda Miles ◽  
Ian Bloor ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Vascular Function ◽  
Rna Degradation ◽  
Whole Body ◽  
Anatomical Location ◽  
High Fat ◽  
Short Term ◽  
Brown Adipose

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n = 12) were fed either a standard (10% fat, n = 6) or high fat diet (HFD: 45% fat, n = 6) for 72 h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72 h induced rapid weight gain (c. 2.6%) and reduced serum NEFA with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and PPAR signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g. Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.

scholarly journals Interscapular and Perivascular Brown Adipose Tissue Respond Differently to a Short-Term High-Fat Diet

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1065 ◽  
Author(s):  
Peter Aldiss ◽  
Jo E. Lewis ◽  
David J. Boocock ◽  
Amanda K. Miles ◽  
Ian Bloor ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
High Fat Diet ◽  
Vascular Function ◽  
Rna Degradation ◽  
Whole Body ◽  
Anatomical Location ◽  
High Fat ◽  
Short Term ◽  
Brown Adipose

Brown adipose tissue (BAT) function may depend on its anatomical location and developmental origin. Interscapular BAT (iBAT) regulates acute macronutrient metabolism, whilst perivascular BAT (PVAT) regulates vascular function. Although phenotypically similar, whether these depots respond differently to acute nutrient excess is unclear. Given their distinct anatomical locations and developmental origins and we hypothesised that iBAT and PVAT would respond differently to brief period of nutrient excess. Sprague-Dawley rats aged 12 weeks (n=12) were fed either a standard (10% fat, n=6) or high fat diet (HFD: 45% fat, n=6) for 72h and housed at thermoneutrality. Following an assessment of whole body physiology, fat was collected from both depots for analysis of gene expression and the proteome. HFD consumption for 72h induced rapid weight gain (c. 2.6%) and reduced serum non-esterified fatty acids (NEFA) with no change in either total adipose or depot mass. In iBAT, an upregulation of genes involved in insulin signalling and lipid metabolism was accompanied by enrichment of lipid-related processes and functions, plus glucagon and peroxisome proliferator-activated receptor (PPAR) signalling pathways. In PVAT, HFD induced a pronounced down-regulation of multiple metabolic pathways which was accompanied with increased abundance of proteins involved in apoptosis (e.g., Hdgf and Ywaq) and toll-like receptor signalling (Ube2n). There was also an enrichment of DNA-related processes and functions (e.g., nucleosome assembly and histone exchange) and RNA degradation and cell adhesion pathways. In conclusion, we show that iBAT and PVAT elicit divergent responses to short-term nutrient excess highlighting early adaptations in these depots before changes in fat mass.

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