Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance

Nishimoto, Sei‐ichi; Fukuda, Daiju; Higashikuni, Yasutomi; Tanaka, Kimie; Hirata, Yoichiro; Murata, Chie; Kim‐Kaneyama, Joo‐ri; Sato, Fukiko; Bando, Masahiro; Yagi, Shusuke; Soeki, Takeshi; Hayashi, Toshio; Imoto, Issei; Sakaue, Hiroshi; Shimabukuro, Michio; Sata, Masataka

doi:10.1126/sciadv.1501332

Cited by 220 publications

(212 citation statements)

References 53 publications

Supporting

Mentioning

200

Contrasting

Order By: Relevance

“…Cell-free DNA is present in small amounts in the blood of healthy individuals, but its concentration is increased in patients suffering from chronic diseases. In this context, studies suggest that it acts as a contributor to chronic diseases by inducing inflammation via TLR9, a PRR classically activated by unmethylated CpG motifcontaining bacterial and viral DNA fragments (Chan & Lo 2002, Breitbach et al 2012, Nishimoto et al 2016. Mitochondrial DNA also triggers TLR9 to induce inflammation .…”

Section: Cell-free Dnamentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

View full text Add to dashboard Cite

Inflammation is essential for successful embryo implantation, pregnancy maintenance and delivery. In the last decade, important advances have been made in regard to endogenous, and therefore non-infectious, initiators of inflammation, which can act through the same receptors as pathogens. These molecules are referred to as damage-associated molecular patterns (DAMPs), and their involvement in reproduction has only recently been unraveled. Even though inflammation is necessary for successful reproduction, untimely activation of inflammatory processes can have devastating effect on pregnancy outcomes. Many DAMPs, such as uric acid, high-mobility group box 1 (HMGB1), interleukin (IL)-1 and cell-free fetal DNA, have been associated with pregnancy complications, such as miscarriages, preeclampsia and preterm birth in preclinical models and in humans. However, the specific contribution of alarmins to these conditions is still under debate, as currently there is lack of information on their mechanism of action. In this review, we discuss the role of sterile inflammation in reproduction, including early implantation and pregnancy complications. Particularly, we focus on major alarmins vastly implicated in numerous sterile inflammatory processes, such as uric acid, HMGB1, IL-1α and cell-free DNA (especially that of fetal origin) while giving an overview of the potential role of other candidate alarmins.Reproduction (2016) 152 R277-R292

show abstract

Section: Cell-free Dnamentioning

confidence: 99%

Sterile inflammation and pregnancy complications: a review

Nadeau-Vallée¹,

Obari²,

Palacios³

et al. 2016

Reproduction

219

161

View full text Add to dashboard Cite

show abstract

“…Many factors have been suggested as possible initiators of recruitment including fatty acid flux (8), abnormal adipokine secretion, and cell-free DNA from adipocytes (9). In recent years, enhanced adipocyte death has been attracting increasing attention.…”

Section: Adipocyte Death and Macrophage Infiltra-tionmentioning

confidence: 99%

Adipocyte Death and Chronic Inflammation in Obesity

Kuroda

Sakaue

2017

J. Med. Invest.

Self Cite

View full text Add to dashboard Cite

: Cell death is closely linked to many diseases including cancer, neurodegenerative diseases, autoimmune diseases, and metabolic disorders. Increased adipocyte death has been reported during the development of obesity. Adipocyte death may be caused by excessive stress during obesity-related adipose tissue remodeling. Adipose tissue macrophages are key players in obesity-related inflammation and systemic insulin resistance. Accumulating evidence suggests that adipocyte death is involved in immune cell function and initiates inflammation through an interaction with macrophages ; however, the precise mechanisms remain largely unknown.This review focuses on the contribution of dead cells (particularly dead adipocytes in adipose tissue) to the pathophysiological conditions associated with obesity. J. Med. Invest.

show abstract

“…Chronic low-grade inflammation in adipose tissue leads to insulin resistance and various pathological responses [1][2][3]. The anti-inflammatory adipocytokine adiponectin has been found to be closely associated with insulin resistance and cardiovascular disease [4][5][6][7].…”

Section: Introductionmentioning

confidence: 99%

Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism

Wang

Zhou

et al. 2016

Cell Physiol Biochem

View full text Add to dashboard Cite

Background/Aims: Extensive research has explored the role of aldosterone in insulin resistance. Recent evidence suggests that the mineralocorticoid receptor (MR) mediates aldosterone-induced dysregulation of cytokines, and most of this research has focused on adjustments in fat tissue and adipocytes. However, the direct effect of MR blockade on insulin resistance in cardiomyocytes remains largely unknown. In the present study, we investigated whether MR blockade improves insulin-sensitizing factors in insulin-resistant rats and attenuates the dysregulation of the aldosterone-related transport of adiponectin and glucose in cardiomyocytes and examined the underlying mechanisms. Methods: The effects of aldosterone, MR inhibitors (e.g., eplerenone), a peroxisome proliferator-activated receptor (PPAR) α agonist, and a p38 mitogen-activated protein kinase (MAPK) inhibitor on adiponectin and glucose transport were studied at the mRNA and protein levels in vitro and in vivo. Results: Our data revealed that aldosterone reduced the expression of adiponectin and inhibited the transport of glucose in cardiomyocytes and that MR blockade reversed these affects. In vivo, MR blockade improved insulin-sensitive parameters and increased adiponectin expression in the myocardia of high-fat diet rats. Furthermore, aldosterone promoted p38MAPK expression but negatively affected PPARα expression, and the downregulation of adiponectin by aldosterone was reversed by MR blockade, a PPARα agonist, and a p38 MAPK inhibitor. Conclusion: The above results suggested that aldosterone promoted insulin resistance in the heart and that this effect could be partly reversed by MR blockade through signal transduction in the P38 MAPK pathway and PPARα.

show abstract

Obesity-induced DNA released from adipocytes stimulates chronic adipose tissue inflammation and insulin resistance

Abstract: DNA released from obesity-induced degenerated adipocytes stimulates inflammation in adipose tissue and insulin resistance.

Cited by 220 publications

References 53 publications

Sterile inflammation and pregnancy complications: a review

Sterile inflammation and pregnancy complications: a review

Adipocyte Death and Chronic Inflammation in Obesity

Mineralocorticoid Receptor Blockade Improves Insulin Sensitivity in the Rat Heart and a Possible Molecular Mechanism

Contact Info

Product

Resources

About