Obesity and Systemic Inflammation: Insights into Epigenetic Mechanisms

Kaliman, Perla; Párrizas, Marcelina

doi:10.5772/22463

Cited by 5 publications

(3 citation statements)

References 175 publications

(159 reference statements)

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“…This condition has been connected with the onset and evolution of age-related diseases, including type 2 diabetes mellitus, cardiovascular disease, cancer and neurodegeneration [2-4]. Indeed, the aging brain exhibits a progressive increase in inflammatory processes [5], which can be neurotoxic, altering important central functions [6] and contributing to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD) [7].…”

Section: Introductionmentioning

confidence: 99%

“…The process of aging is associated with a low-grade systemic inflammation defined as inflammaging [ 1 ], which is characterized by an increase of acute-phase circulating proteins and proinflammatory factors such as interleukin (IL)-6 and tumor necrosis factor (TNF-α). This condition has been connected with the onset and evolution of age-related diseases, including type 2 diabetes mellitus, cardiovascular disease, cancer and neurodegeneration [ 2 - 4 ]. Indeed, the aging brain exhibits a progressive increase in inflammatory processes [ 5 ], which can be neurotoxic, altering important central functions [ 6 ] and contributing to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD) [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Rcor2 underexpression in senescent mice: a target for inflammaging?

Álvarez-López

Molina-Martínez

Castro

et al. 2014

J Neuroinflammation

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BackgroundAging is characterized by a low-grade systemic inflammation that contributes to the pathogenesis of neurodegenerative disorders such as Alzheimer’s disease (AD). However, little knowledge is currently available on the molecular processes leading to chronic neuroinflammation. In this context, recent studies have described the role of chromatin regulators in inflammation and longevity including the REST corepressor (Rcor)-2 factor, which seems to be involved in an inflammatory suppressive program.MethodsTo assess the impact of Rcor2 in age-related inflammation, gene expression levels were quantified in different tissues and ages of the spontaneous senescence-accelerated P8 mouse (P8) using the SAMR1 mouse (R1) as a control. Specific siRNA transfection in P8 and R1 astrocyte cultures was used to determine Rcor2 involvement in the modulation of neuroinflammation. The effect of lipopolysaccharide (LPS) treatment on Rcor2 levels and neuroinflammation was analyzed both in vivo and in vitro.ResultsP8 mice presented a dramatic decrease in Rcor2 gene expression compared with R1 controls in splenocytes, an alteration also observed in the brain cortex, hippocampus and primary astrocytes of these mice. Rcor2 reduction in astrocytes was accompanied by an increased basal expression of the interleukin (Il)-6 gene. Strikingly, intraperitoneal LPS injection in R1 mice downregulated Rcor2 in the hippocampus, with a concomitant upregulation of tumor necrosis factor (Tnf-α), Il1-β and Il6 genes. A negative correlation between Rcor2 and Il6 gene expression was also verified in LPS-treated C6 glioma cells. Knock down of Rcor2 by siRNA transfection (siRcor2) in R1 astrocytes upregulated Il6 gene expression while siRcor2 further increased Il6 expression in P8 astrocytes. Moreover, LPS activation provoked a further downregulation of Rcor2 and an amplified induction of Il6 in siRcor2-tranfected astrocytes.ConclusionsData presented here show interplay between Rcor2 downregulation and increased inflammation and suggest that Rcor2 may be a key regulator of inflammaging.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Rcor2 underexpression in senescent mice: a target for inflammaging?

Álvarez-López

Molina-Martínez

Castro

et al. 2014

J Neuroinflammation

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“…tissue inflammation and decrease in insulin sensitivity are also associated with CD4 tissue cell population (Kaliman & Parrizas, 2011). Interaction between dysfunctional adipose tissues, activated T cells, and chemokines leads to dysregulation of adipokines (Holvoet, 2012), by overexpression of resistin, leptin and reduction of adiponectin levels (Holvoet, 2012;Torres-Leal et al, 2012).…”

Section: Dysfunctional Adipose Tissues Caused By Obesitymentioning

confidence: 99%

Adiponectin is partially associated with exosomes in mouse serum

Phoonsawat

Aoki-Yoshida

Tsuruta

et al. 2014

Biochemical and Biophysical Research Communications

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Previous studies suggest that adipocyte-derived exosomes play a role in cell-to-cell communication during the development of metabolic diseases. However, the characteristics and function of exosomes released from adipocytes in vivo remain to be elucidated. Clearly, exosomes released from adipocytes could exist in the circulation. In addition, because the composition of exosomes is heterogenic, depending on the cellular origin of the exosome, adipocyte-derived exosomes could be accompanied by molecules produced specifically in adipocytes. In this context, this study postulated that such molecules associated with exosomes in the serum could be markers for adipocyte-derived exosomes in vivo. This study particularly focused on secretory proteins produced specifically in adipocytes, namely adipocytokines including adiponectin, leptin, and resistin. Serum adiponectin is partially associated with exosomesBased on western blotting, CD63, a well-known protein marker of exosomes, was concentrated in the pellet of mouse serum after ultracentrifugation, suggesting successful isolation of exosomes. Western blotting detected adiponectin but no leptin and only trace amounts of resistin in the exosome fraction. After ultracentrifugation on a discontinuous gradient, both adiponectin and CD63 were detected in a fraction at a density of 1.17 g/mL, consistent with the density of exosomes. The adiponectin signal in the exosome fraction was decreased by proteinase K treatment and completely quenched by a combination of proteinase K and Triton X-100. These results suggest that a portion of adiponectin exists as a transmembrane protein in the exosomes in mouse serum. showed that the concentration of adiponectin in the serum and the ratio of adiponectin to total protein in the exosome fraction were lower in obese mice than in lean mice.In conclusion, this study showed that serum adiponectin is partially associated with exosomes in mice. Considering that adiponectin is produced exclusively by adipocytes, adiponectin-associated exosomes in serum could be derived from adipocytes. This study proposes that adiponectin could be a marker for exosomes released from adipocytes in vivo.iii

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