Study of insulin resistance and chronic inflammation in cybrid cells harboring diabetes-susceptible mitochondrial haplogroups

Background The relationship between tumor necrosis factor (TNF)-related parameters and cardiorenal metabolic factors is still controversial in clinical hypertension. Methods Normotensive men (NT, n=60) and treated stage 2 and 3 essential hypertensive men (HT, n=89) were enrolled in this study. The relationship between TNF-related parameters and cardiorenal metabolic factors was examined in NT and HT, separately. Results HT showed higher rates of insulin resistance and enhanced chronic inflammation compared with NT. The levels of soluble TNF receptor 1 and 2 were significantly higher in HT than in NT, although TNF-α levels were unexpectedly lower in HT than in NT. Regression analysis indicated that the TNF-related parameters were closely linked with mild renal dysfunction both in NT and HT, and moderately related to chronic inflammation only in HT. HT taking inhibitors of the renin-angiotensin system showed improved insulin resistance, but no difference in the TNF-related parameters. Conclusion These results suggest that the disturbed TNF system is closely linked with chronic inflammation rather than with insulin resistance in HT.

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MicroRNAs link chronic inflammation in childhood to growth impairment and insulin-resistance

Cytokine & Growth Factor Reviews ◽

10.1016/j.cytogfr.2017.12.004 ◽

2018 ◽

Vol 39 ◽

pp. 1-18 ◽

Cited By ~ 8

Author(s):

Francesca Cirillo ◽

Pietro Lazzeroni ◽

Cecilia Catellani ◽

Chiara Sartori ◽

Sergio Amarri ◽

...

Keyword(s):

Insulin Resistance ◽

Chronic Inflammation ◽

Growth Impairment

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Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

BMJ Open Diabetes Research & Care ◽

10.1136/bmjdrc-2019-000783 ◽

2019 ◽

Vol 7 (1) ◽

pp. e000783 ◽

Cited By ~ 7

Author(s):

Liang Xu ◽

Naoto Nagata ◽

Guanliang Chen ◽

Mayumi Nagashimada ◽

Fen Zhuge ◽

...

Keyword(s):

Insulin Resistance ◽

Weight Gain ◽

Energy Expenditure ◽

Chronic Inflammation ◽

Plasma Levels ◽

High Fat Diet ◽

Macrophage Activation ◽

Low Grade ◽

Obese Mice ◽

High Fat

ObjectiveWe reported previously that empagliflozin—a sodium-glucose cotransporter (SGLT) 2 inhibitor—exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice.Research design and methodsAfter 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin.ResultsTreatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation.ConclusionsTreatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.

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Relationship of Androgens to Insulin Resistance and Chronic Inflammation in Morbidly Obese Premenopausal Women: Studies before and after Vertical Banded Gastroplasty

Obesity Surgery ◽

10.1381/096089206778392130 ◽

2006 ◽

Vol 16 (9) ◽

pp. 1214-1220 ◽

Cited By ~ 18

Author(s):

Hans-Peter Kopp ◽

Katharina Krzyzanowska ◽

Gerit-Holger Schernthaner ◽

Stefan Kriwanek ◽

Guntram Schernthaner

Keyword(s):

Insulin Resistance ◽

Chronic Inflammation ◽

Vertical Banded Gastroplasty ◽

Premenopausal Women ◽

Morbidly Obese ◽

Women Studies ◽

Banded Gastroplasty ◽

Before And After ◽

Relationship Of

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Abstract: P1232 INSULIN RESISTANCE, CHRONIC INFLAMMATION AND MUSCLE WASTING IN END-STAGE RENAL DISEASE PATIENTS ON HEMODIALYSIS

Atherosclerosis Supplements ◽

10.1016/s1567-5688(09)71249-8 ◽

2009 ◽

Vol 10 (2) ◽

pp. e1287

Author(s):

Z Rasic-Milutinovic ◽

G Perunicic-Pekovic ◽

L Bokan

Keyword(s):

Insulin Resistance ◽

Renal Disease ◽

Chronic Inflammation ◽

End Stage Renal Disease ◽

Muscle Wasting ◽

Stage Renal Disease ◽

End Stage

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Bacterial Endotoxin Activity in Human Serum Is Associated With Dyslipidemia, Insulin Resistance, Obesity, and Chronic Inflammation

Diabetes Care ◽

10.2337/dc10-2197 ◽

2011 ◽

Vol 34 (8) ◽

pp. 1809-1815 ◽

Cited By ~ 214

Author(s):

Mariann I. Lassenius ◽

Kirsi H. Pietiläinen ◽

Kati Kaartinen ◽

Pirkko J. Pussinen ◽

Jaana Syrjänen ◽

...

Keyword(s):

Insulin Resistance ◽

Human Serum ◽

Chronic Inflammation ◽

Bacterial Endotoxin ◽

Endotoxin Activity

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Macrophage TCF-4 co-activates p65 to potentiate chronic inflammation and insulin resistance in mice

Clinical Science ◽

10.1042/cs20160192 ◽

2016 ◽

Vol 130 (14) ◽

pp. 1257-1268 ◽

Cited By ~ 5

Author(s):

Xia Kang ◽

Along Hou ◽

Rui Wang ◽

Da Liu ◽

Wei Xiang ◽

...

Keyword(s):

Insulin Resistance ◽

Chronic Inflammation ◽

Proinflammatory Cytokines ◽

Blood Monocytes ◽

Mrna Transcription ◽

Enhanced Expression ◽

Factor Α ◽

Transcription Factor 4 ◽

Interfering Rna

Transcription factor 4 (TCF-4) was recently identified as a candidate gene for the cause of type 2 diabetes, although the mechanisms have not been fully elucidated. In the present study, we demonstrated that the TCF-4 transgene in macrophages aggravated high-fat diet (HFD)-induced insulin resistance and chronic inflammation, characterized by the elevation of proinflammatory cytokines in the blood, liver and white adipose tissue, as well as a proinflammatory profile of immune cells in visceral fats in mice. Mechanistically, TCF-4 functioned as a co-activator of p65 to amplify the saturated free fatty acid (FFA)-stimulated promoter activity, mRNA transcription and secretion of proinflammatory cytokines in primary macrophages. Blockage of p65 with a specific interfering RNA or inhibitor could prevent TCF-4-enhanced expression of proinflammatory cytokines in FFA/lipopolysaccharide-treated primary macrophages. The p65 inhibitor could abolish macrophage TCF-4 transgene-aggravated systemic inflammation, glucose intolerance and insulin resistance in HFD-treated mice. In addition, we demonstrated that the mRNA expression of TCF-4 in the peripheral blood monocytes from humans was positively correlated to the levels of interleukin (IL)-1β, tumour necrosis factor α, IL-6 and fasting plasma glucose. In summary, we identified TCF-4 as a co-activator of p65 in the potentiation of proinflammatory cytokine production in macrophages and aggravation of HFD-induced chronic inflammation and insulin resistance in mice.

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