scholarly journals Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults

Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1342
Author(s):  
Esther C. Gallegos-Cabriales ◽  
Ernesto Rodriguez-Ayala ◽  
Hugo A. Laviada-Molina ◽  
Edna J. Nava-Gonzalez ◽  
Rocío A. Salinas-Osornio ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Precision Medicine ◽  
Time Course ◽  
Clinical Medicine ◽  
Whole Body ◽  
Low Grade ◽  
Shotgun Lipidomics ◽  
Medicine Research ◽  
P Gene

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals.

Rapid changes in metabolic cold defense and GDP binding to brown adipose tissue mitochondria of rat pups

1993 ◽  
Vol 264 (5) ◽  
pp. R1017-R1023 ◽  
Author(s):  
G. Kortner ◽  
K. Schildhauer ◽  
O. Petrova ◽  
I. Schmidt
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Time Course ◽  
Developmental Changes ◽  
Whole Body ◽  
Rat Pups ◽  
Brown Adipose ◽  
Rapid Changes ◽  
Whole Body Metabolism

To determine developmental changes of brown adipose tissue (BAT) thermogenic activity at defined circadian and thermal states, we evaluated the time course of cold-induced increases of in vitro guanosine 5'-diphosphate (GDP) binding in parallel with whole body metabolism (oxygen consumption, VO2) and core temperature (Tc) in 1- to 11-day-old rat pups. During the maximum phase of the juvenile diurnal cycle, Tc of littermates was recorded continuously and VO2 alternately until 2 min before animals were killed for removal of interscapular BAT. GDP binding after 1.5 h at thermoneutrality and its increase during physiologically comparable cold loads were significantly lower in 1-day-old pups than in 5- and 11-day-old pups. Cold defense was activated more rapidly in the older pups, but GDP binding in even the 1-day-old pups was significantly increased during the second 10-min period of cold exposure. We conclude that rapid changes in thermogenic activity, in connection with the known developmental changes in the dependence of the suckling rat's metabolic cold defense on maternal and sibling contact and circadian phase, will distort longitudinal studies of any fast-changing BAT parameter when the conditions immediately before tissue removal are not thoroughly controlled.

scholarly journals Roles of Adipokines in Digestive Diseases: Markers of Inflammation, Metabolic Alteration and Disease Progression

2020 ◽  
Vol 21 (21) ◽  
pp. 8308
Author(s):  
Ming-Ling Chang ◽  
Zinger Yang ◽  
Sien-Sing Yang
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Whole Body ◽  
Low Grade ◽  
Colon Polyps ◽  
Alcoholic Fatty Liver ◽  
Global Epidemic ◽  
Markers Of Inflammation ◽  
Digestive Diseases ◽  
Digestive Cancers

Adipose tissue is a highly dynamic endocrine tissue and constitutes a central node in the interorgan crosstalk network through adipokines, which cause pleiotropic effects, including the modulation of angiogenesis, metabolism, and inflammation. Specifically, digestive cancers grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes are reprogrammed into cancer-associated adipocytes and secrete adipokines to affect tumor cells. Moreover, the liver is the central metabolic hub. Adipose tissue and the liver cooperatively regulate whole-body energy homeostasis via adipokines. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemic and is related to low-grade systemic inflammation characterized by altered adipokine regulation. Obesity-related digestive diseases, including gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, viral hepatitis-related diseases, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes, might cause specific alterations in adipokine profiles. These patterns and associated bases potentially contribute to the identification of prognostic biomarkers and therapeutic approaches for the associated digestive diseases. This review highlights important findings about altered adipokine profiles relevant to digestive diseases, including hepatic, pancreatic, gastrointestinal, and biliary tract diseases, with a perspective on clinical implications and mechanistic explorations.

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 Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle

2009 ◽  
Vol 201 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Camilla Alexanderson ◽  
Elias Eriksson ◽  
Elisabet Stener-Victorin ◽  
Malin Lönn ◽  
Agneta Holmäng
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Uncoupling Protein ◽  
Female Rats ◽  
Whole Body ◽  
Low Grade ◽  
Expression Of Genes ◽  
Genes Encoding

Early postnatal events can predispose to metabolic and endocrine disease in adulthood. In this study, we evaluated the programming effects of a single early postnatal oestradiol injection on insulin sensitivity in adult female rats. We also assessed the expression of genes involved in inflammation and glucose metabolism in skeletal muscle and adipose tissue and analysed circulating inflammation markers as possible mediators of insulin resistance. Neonatal oestradiol exposure reduced insulin sensitivity and increased plasma levels of monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1. In skeletal muscle, oestradiol increased the expression of genes encoding complement component 3 (C3), Mcp-1, retinol binding protein-4 (Rbp4) and transforming growth factor β1 (Tgfβ1). C3 and MCP-1 are both related to insulin resistance, and C3, MCP-1 and TGFβ1 are also involved in inflammation. Expression of genes encoding glucose transporter-4 (Glut 4), carnitine-palmitoyl transferase 1b (Cpt1b), peroxisome proliferator-activated receptor δ (Ppard) and uncoupling protein 3 (Ucp3), which are connected to glucose uptake, lipid oxidation, and energy uncoupling, was down regulated. Expression of several inflammatory genes in skeletal muscle correlated negatively with whole-body insulin sensitivity. In s.c. inguinal adipose tissue, expression of Tgfβ1, Ppard and C3 was decreased, while expression of Rbp4 and Cpt1b was increased. Inguinal adipose tissue weight was increased but adipocyte size was unaltered, suggesting an increased number of adipocytes. We suggest that early neonatal oestrogen exposure may reduce insulin sensitivity by inducing chronic, low-grade systemic and skeletal muscle inflammation and disturbances of glucose and lipid metabolism in skeletal muscle in adulthood.

scholarly journals MRI Reveals Human Brown Adipose Tissue Is Rapidly Activated in Response to Cold

2019 ◽  
Vol 3 (12) ◽  
pp. 2374-2384 ◽  
Author(s):  
Stephan M Oreskovich ◽  
Frank J Ong ◽  
Basma A Ahmed ◽  
Norman B Konyer ◽  
Denis P Blondin ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Cold Exposure ◽  
Time Course ◽  
Whole Body ◽  
Proton Density ◽  
Fat Percentage ◽  
Similar Time ◽  
Brown Adipose ◽  
Posterior Neck

Abstract Context In rodents, cold exposure induces the activation of brown adipose tissue (BAT) and the induction of intracellular triacylglycerol (TAG) lipolysis. However, in humans, the kinetics of supraclavicular (SCV) BAT activation and the potential importance of TAG stores remain poorly defined. Objective To determine the time course of BAT activation and changes in intracellular TAG using MRI assessment of the SCV (i.e., BAT depot) and fat in the posterior neck region (i.e., non-BAT). Design Cross-sectional. Setting Clinical research center. Patients or Other Participants Twelve healthy male volunteers aged 18 to 29 years [body mass index = 24.7 ± 2.8 kg/m2 and body fat percentage = 25.0% ± 7.4% (both, mean ± SD)]. Intervention(s) Standardized whole-body cold exposure (180 minutes at 18°C) and immediate rewarming (30 minutes at 32°C). Main Outcome Measure(s) Proton density fat fraction (PDFF) and T2* of the SCV and posterior neck fat pads. Acquisitions occurred at 5- to 15-minute intervals during cooling and subsequent warming. Results SCV PDFF declined significantly after only 10 minutes of cold exposure [−1.6% (SE: 0.44%; P = 0.007)] and continued to decline until 35 minutes, after which time it remained stable until 180 minutes. A similar time course was also observed for SCV T2*. In the posterior neck fat (non-BAT), there were no cold-induced changes in PDFF or T2*. Rewarming did not result in a change in SCV PDFF or T2*. Conclusions The rapid cold-induced decline in SCV PDFF suggests that in humans BAT is activated quickly in response to cold and that TAG is a primary substrate.

scholarly journals Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Christine Bourgeois ◽  
Jennifer Gorwood ◽  
Anaelle Olivo ◽  
Laura Le Pelletier ◽  
Jacqueline Capeau ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hiv Infection ◽  
Systemic Inflammation ◽  
Immune Cells ◽  
The Body ◽  
Whole Body ◽  
Viral Reservoir ◽  
Low Grade ◽  
Endocrine Activity ◽  
Inflammatory Signals

White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity. Several of AT’s intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. In obesity, the concomitant pro-inflammatory signals produced by immune cells, adipocytes and adipose stem cells help to drive local inflammation in a vicious circle. Although the secretion of adipokines by AT is a prime contributor to systemic inflammation, the lipotoxicity associated with AT dysfunction might also be involved and could affect distant organs. In HIV-infected patients, the AT is targeted by both HIV infection and antiretroviral therapy (ART). During the primary phase of infection, the virus targets AT directly (by infecting AT CD4 T cells) and indirectly (via viral protein release, inflammatory signals, and gut disruption). The initiation of ART drastically changes the picture: ART reduces viral load, restores (at least partially) the CD4 T cell count, and dampens inflammatory processes on the whole-body level but also within the AT. However, ART induces AT dysfunction and metabolic side effects, which are highly dependent on the individual molecules and the combination used. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA and induce oxidative stress and adipocyte death. Protease inhibitors predominantly affect metabolic pathways (affecting adipogenesis and adipocyte homeostasis) resulting in insulin resistance. Recently marketed integrase strand transfer inhibitors induce both adipocyte adipogenesis, hypertrophy and fibrosis. It is challenging to distinguish between the respective effects of viral persistence, persistent immune defects and ART toxicity on the inflammatory profile present in ART-controlled HIV-infected patients. The host metabolic status, the size of the pre-established viral reservoir, the quality of the immune restoration, and the natural ageing with associated comorbidities may mitigate and/or reinforce the contribution of antiretrovirals (ARVs) toxicity to the development of low-grade inflammation in HIV-infected patients. Protecting AT functions appears highly relevant in ART-controlled HIV-infected patients. It requires lifestyle habits improvement in the absence of effective anti-inflammatory treatment. Besides, reducing ART toxicities remains a crucial therapeutic goal.

Innate immunity orchestrates adipose tissue homeostasis

2017 ◽  
Vol 31 (1) ◽  
Author(s):  
Yi-Wei Lin ◽  
Li-Na Wei
Keyword(s):  
Insulin Resistance ◽  
Innate Immunity ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Inflammatory Cells ◽  
Whole Body ◽  
M2 Macrophage ◽  
Low Grade ◽  
Metabolic Complications ◽  
M1 Macrophage

AbstractObesity is strongly associated with multiple diseases including insulin resistance, type 2 diabetes, cardiovascular diseases, fatty liver disease, neurodegenerative diseases and cancers, etc. Adipose tissue (AT), mainly brown AT (BAT) and white AT (WAT), is an important metabolic and endocrine organ that maintains whole-body homeostasis. BAT contributes to non-shivering thermogenesis in a cold environment; WAT stores energy and produces adipokines that fine-tune metabolic and inflammatory responses. Obesity is often characterized by over-expansion and inflammation of WAT where inflammatory cells/mediators are abundant, especially pro-inflammatory (M1) macrophages, resulting in chronic low-grade inflammation and leading to insulin resistance and metabolic complications. Macrophages constitute the major component of innate immunity and can be activated as a M1 or M2 (anti-inflammatory) phenotype in response to environmental stimuli. Polarized M1 macrophage causes AT inflammation, whereas polarized M2 macrophage promotes WAT remodeling into the BAT phenotype, also known as WAT browning/beiging, which enhances insulin sensitivity and metabolic health. This review will discuss the regulation of AT homeostasis in relation to innate immunity.

scholarly journals Subacute Endotoxemia Induces Adipose Inflammation and Changes in Lipid and Lipoprotein Metabolism in Cats

Endocrinology ◽  
2011 ◽  
Vol 152 (3) ◽  
pp. 804-815 ◽  
Author(s):  
M. Osto ◽  
E. Zini ◽  
M. Franchini ◽  
C. Wolfrum ◽  
F. Guscetti ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Adipose Tissue ◽  
Whole Body ◽  
Low Grade ◽  
Model Assessment ◽  
Insulin Metabolism ◽  
Tissue Specific ◽  
Markers Of Inflammation ◽  
Adipose Tissue Dysfunction

Acute inflammation in humans is associated with transient insulin resistance (IR) and dyslipidemia. Chronic low-grade inflammation is a pathogenic component of IR and adipose tissue dysfunction in obesity-induced type 2 diabetes. Because feline diabetes closely resembles human type 2 diabetes, we studied whether lipopolysaccharide (LPS)-induced subacute inflammation, in the absence of obesity, is the potential primary cause of IR and metabolic disorders. Cats received increasing iv doses (10–1000 ng/kg−1 · h−1) of LPS (n = 5) or saline (n = 5) for 10 d. Body temperature, proinflammatory and metabolic markers, and insulin sensitivity were measured daily. Tissue mRNA and protein expression were quantified on d 10. LPS infusion increased circulating and tissue markers of inflammation. Based on the homeostasis model assessment, endotoxemia induced transient IR and β-cell dysfunction. At the whole-body level, IR reverted after the 10-d treatment; however, tissue-specific indications of IR were observed, such as down-regulation of adipose glucose transporter 4, hepatic peroxisome proliferative activated receptor-γ1 and -2, and muscle insulin receptor substrate-1. In adipose tissue, increased hormone-sensitive lipase activity led to reduced adipocyte size, concomitant with increased plasma and hepatic triglyceride content and decreased total and high-density lipoprotein cholesterol levels. Prolonged LPS-induced inflammation caused acute IR, followed by long-lasting tissue-specific dysfunctions of lipid-, glucose-, and insulin metabolism-related targets; this ultimately resulted in dyslipidemia but not whole-body IR. Endotoxemia in cats may provide a promising model to study the cross talk between metabolic and inflammatory responses in the development of adipose tissue dysfunction and IR.

scholarly journals The Endocrine Role of Adipose Tissue and Its Management of Obesity-Related Diseases.

2020 ◽  
pp. 1-2
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid Esters ◽  
Whole Body ◽  
Low Grade ◽  
Endocrine Organ ◽  
Hydroxyl Fatty Acids ◽  
Body Energy ◽  
Low Grade Inflammation ◽  
Acid Esters

Adipose tissue plays a central role in regulating whole-body energy. Moreover, adipose tissue acts as an endocrine organ and produces numerous bioactive factors called adipokines which communicate with other organs and modulate a range of metabolic pathways: proteins (adiponectin, angiopoietins, chemerin, etc.), lipids (fatty acid esters of hydroxyl fatty acids, lysophosphatidic acids and sphingolipids), metabolites (uric acid and uridine) and microRNAs. However, excessive adipose tissue is associated with a chronic state of low-grade inflammation, caused by unbalanced production or secretion of these adipokines and can contribute to the development of obesity [1].

scholarly journals STAT1 dissociates adipose tissue inflammation from insulin sensitivity in obesity

2020 ◽  
Author(s):  
Ada Admin ◽  
Aaron R. Cox ◽  
Natasha Chernis ◽  
David A. Bader ◽  
Pradip K Saha ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Tca Cycle ◽  
Whole Body ◽  
Low Grade ◽  
Type I ◽  
Obese Mice ◽  
Fat Cell ◽  
Relationship Of

Obesity fosters low-grade inflammation in white adipose tissue (WAT) that may contribute to the insulin resistance that characterizes type 2 diabetes mellitus (T2DM). However, the causal relationship of these events remains unclear. The established dominance of signal transducer and activator of transcription 1 (STAT1) function in the immune response suggests an obligate link between inflammation and the co-morbidities of obesity. To this end, we sought to determine how STAT1 activity in white adipocytes affects insulin sensitivity. STAT1 expression in WAT inversely correlated with fasting plasma glucose in both obese mice and humans. Metabolomic and gene expression profiling established STAT1 deletion in adipocytes (<i>STAT1<sup>a-KO­­­</sup></i>) enhanced mitochondrial function and accelerated TCA cycle flux coupled with reduced fat cell size in subcutaneous WAT depots. <i>STAT1<sup>a-KO</sup></i> reduced WAT inflammation, but insulin resistance persisted in obese mice. Rather, elimination of type I cytokine interferon gamma (IFNg) activity enhanced insulin sensitivity in diet-induced obesity. Our findings reveal a permissive mechanism that bridges WAT inflammation to whole-body insulin sensitivity.

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