Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity

Lee, Byung-Cheol; Kim, Myung-Sunny; Pae, Munkyong; Yamamoto, Yasuhiko; Eberlé, Delphine; Shimada, Takeshi; Kamei, Nozomu; Park, Hee-Sook; Sasorith, Souphatta; Woo, Ju Rang; You, Jichun; Mosher, William D.; Brady, Hugh J.M.; Shoelson, Steven E.; Lee, Jongsoon

doi:10.1016/j.cmet.2016.03.002

Cited by 243 publications

(304 citation statements)

References 47 publications

(58 reference statements)

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“…iNKT cells may be involved in adipose tissue inflammation, because reduced numbers have been associated with obesity and metabolic disturbances in patients [72]. Moreover, it has been recently demonstrated that adipose tissue natural killer (NK) cells control macrophages as an upstream regulator most likely through pro-inflammatory mediators including TNFα [73]. Both genetic and pharmacological depletion of NK cells significantly reduced adipose tissue macrophage numbers and improved obesity-induced insulin resistance [73].…”

Section: Autophagy Apoptosis and Immune Cell Infiltration In Adiposementioning

confidence: 99%

“…Moreover, it has been recently demonstrated that adipose tissue natural killer (NK) cells control macrophages as an upstream regulator most likely through pro-inflammatory mediators including TNFα [73]. Both genetic and pharmacological depletion of NK cells significantly reduced adipose tissue macrophage numbers and improved obesity-induced insulin resistance [73]. T-cells including CD8(+) cells could play an important role in the switch of macrophage subtypes from an M2-alternatively activated macrophage state to an M1-inflammatory macrophagedominated milieu [33,74].…”

Section: Autophagy Apoptosis and Immune Cell Infiltration In Adiposementioning

confidence: 99%

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Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

2016

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The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for noncommunicable diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal disorders and some cancers. Insulin resistance may link accumulation of adipose tissue in obesity to metabolic diseases, although the underlying mechanisms are not completely understood. In the past decades, data from human studies and transgenic animal models strongly suggested correlative, but also causative associations between activation of proinflammatory pathways and insulin resistance. Particularly chronic inflammation in adipose tissue seems to play an important role in the development of obesity-related insulin resistance. On the other hand, adipose tissue inflammation has been shown to be essential for healthy adipose tissue expansion and remodelling. However, whether adipose tissue inflammation represents a consequence or a cause of impaired insulin sensitivity remains an open question. A better understanding of the molecular pathways linking excess adipose tissue storage to chronic inflammation and insulin resistance may provide the basis for the future development of anti-inflammatory treatment strategies to improve adverse metabolic consequences of obesity. In this review, potential mechanisms of adipose tissue inflammation and how adipose tissue inflammation may cause insulin resistance are discussed.

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Section: Autophagy Apoptosis and Immune Cell Infiltration In Adiposementioning

confidence: 99%

Section: Autophagy Apoptosis and Immune Cell Infiltration In Adiposementioning

confidence: 99%

Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

2016

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“…Tregulatory cells maintain M2 macrophage polarization 188 . Obesity is also associated with increased adipose tissue NK cells that secrete TNF-α and exacerbate HFD induced insulin resistance 189 .…”

Section: Macrophage and Adipocyte Dysfunction In Obese Adipose Tissuementioning

confidence: 99%

Macrophage functions in lean and obese adipose tissue

2017

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Summary Interactions between macrophages and adipocytes influence both metabolism and inflammation. Obesity-induced changes to macrophages and adipocytes lead to chronic inflammation and insulin resistance. This paper reviews the various functions of macrophages in lean and obese adipose tissue and how obesity alters adipose tissue macrophage phenotypes. Metabolic disease and insulin resistance shift the balance between numerous pro- and anti-inflammatory regulators of macrophages and create a feed-forward loop of increasing inflammatory macrophage activation and worsening adipocyte dysfunction. This ultimately leads to adipose tissue fibrosis and diabetes. The molecular mechanisms underlying these processes have therapeutic implications for obesity, metabolic syndrome, and diabetes.

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“…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

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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.

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Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity

Cited by 243 publications

References 47 publications

Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

Macrophage functions in lean and obese adipose tissue

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

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