Calorie restriction and endurance exercise share potent anti-inflammatory function in adipose tissues in ameliorating diet-induced obesity and insulin resistance in mice

Abstract Background : Metabolic inflammation has been considered as an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M 1 -like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has been proven to have excellent anti-inflammatory activity and has therapeutic effects on a variety of inflammatory diseases. Therefore, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods: In this study, the monosodium glutamate (MSG) obese mice model was used. The 6-month-old MSG mice were divided into three groups, which were treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for successive 10 weeks, respectively. Meanwhile, the 6-month-old normal mice without MSG treatment were selected as normal controls. Results: When the obesity model was successfully established, obesity degree, insulin resistance, fasting blood glucose(FBG) and serum lipid profiles were significantly increased. Our results showed that the 10-week administration of piperine (40 mg/kg/d) not only significantly decreased the elevated FBG, serum TC and TG levels, but also enhanced infusion rate in hyperglycemic clamp experiment and improved the oral glucose intolerance as well as abnormal insulin tolerance in adult MSG obese mice. Additionally, piperine significantly decreased the total and differential white blood cell (WBC) count and the serum level of lipopolysaccharide (LPS), pro-inflammatory cytokines such as galectin-3 (Gal-3), interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M 1 -like polarization marker CD11c and Gal-3 in adipose tissues. In addition, the in vitro study showed that piperine inhibited LPS- stimulated polarization of RAW 264.7 cells toward the M 1 phenotype. Conclusions: In summary, these findings demonstrated that piperine could significantly inhibit body weight gain, reduce fat accumulation, rectify glycolipid metabolism disorders, improve severe insulin resistance and ameliorates systemic metabolic inflammation in MSG obesity mice. Our study indicates that piperine, as a potential natural alkaloid, can be used in the treatment of obesity-associated diabetes by delaying the progression of obesity-induced insulin resistance.

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Deletion of PPAR in adipose tissues of mice protects against high fat diet-induced obesity and insulin resistance

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0306743102 ◽

2005 ◽

Vol 102 (17) ◽

pp. 6207-6212 ◽

Cited By ~ 318

Author(s):

J. R. Jones ◽

C. Barrick ◽

K.-A. Kim ◽

J. Lindner ◽

B. Blondeau ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

High Fat ◽

Adipose Tissues ◽

Diet Induced Obesity

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Anti-inflammatory effects of yerba maté extract (Ilex paraguariensis) ameliorate insulin resistance in mice with high fat diet-induced obesity

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2011.01.003 ◽

2011 ◽

Vol 335 (2) ◽

pp. 110-115 ◽

Cited By ~ 65

Author(s):

Demétrius P. Arçari ◽

Waldemar Bartchewsky ◽

Tanila W. dos Santos ◽

Karim A. Oliveira ◽

Carlorine C. DeOliveira ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Ilex Paraguariensis ◽

Yerba Mate ◽

High Fat ◽

Diet Induced Obesity ◽

Anti Inflammatory ◽

Ameliorate Insulin Resistance

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Methotrexate attenuates vascular inflammation through an adenosine-microRNA dependent pathway

eLife ◽

10.7554/elife.58064 ◽

2021 ◽

Vol 10 ◽

Author(s):

Dafeng Yang ◽

Stefan Haemmig ◽

Haoyang Zhou ◽

Daniel Pérez-Cremades ◽

Xinghui Sun ◽

...

Keyword(s):

Insulin Resistance ◽

Vascular Endothelium ◽

Vascular Inflammation ◽

Vascular Diseases ◽

High Dose ◽

Dependent Manner ◽

Diet Induced Obesity ◽

Therapeutic Opportunity ◽

Anti Inflammatory

Endothelial cell (EC) activation is an early hallmark in the pathogenesis of chronic vascular diseases. MicroRNA-181b (MiR-181b) is an important anti-inflammatory mediator in the vascular endothelium affecting endotoxemia, atherosclerosis, and insulin resistance. Herein, we identify that the drug methotrexate (MTX) and its downstream metabolite adenosine exert anti-inflammatory effects in the vascular endothelium by targeting and activating MiR-181b expression. Both systemic and endothelial-specific MiR-181a2b2-deficient mice develop vascular inflammation, white adipose tissue (WAT) inflammation, and insulin resistance in a diet-induced obesity model. Moreover, MTX attenuated diet-induced WAT inflammation, insulin resistance, and EC activation in a MiR-181a2b2-dependent manner. Mechanistically, MTX attenuated cytokine-induced EC activation through a unique adenosine-adenosine receptor A3-SMAD3/4-MiR-181b signaling cascade. These findings establish an essential role of endothelial MiR-181b in controlling vascular inflammation and that restoring MiR-181b in ECs by high dose MTX or adenosine signaling may provide a potential therapeutic opportunity for anti-inflammatory therapy.

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Piperine ameliorates insulin resistance via inhibiting metabolic inflammation in monosodium glutamate-treated obese mice

BMC Endocrine Disorders ◽

10.1186/s12902-020-00617-1 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Chaolong Liu ◽

Yanting Yuan ◽

Ji Zhou ◽

Ruixin Hu ◽

Lixia Ji ◽

...

Keyword(s):

Insulin Resistance ◽

Inflammatory Cytokines ◽

Monosodium Glutamate ◽

The Body ◽

Mrna Levels ◽

Obese Mice ◽

Adipose Tissues ◽

Metabolic Inflammation ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Abstract Background Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M1-like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has excellent anti-inflammatory activities and may be used in the treatment of a variety of inflammatory diseases. In this study, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods Newborn mice were subcutaneously (s.c.) injected with monosodium glutamate (MSG) to establish a diabetes model. After 24 weeks, the MSG obese mice were divided into three groups and treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for 10 successive weeks, respectively. Results The obesity model was successfully established, as the body weight, insulin resistance, fasting blood glucose (FBG) and dyslipidemia were significantly increased. The 10-week administration of piperine to the obese mice not only significantly decreased the elevated FBG (Model: 6.45 ± 0.41 mM; Piperine: 4.72 ± 0.44 mM, p < 0.01), serum TC (Model: 5.66 ± 0.66 mM; Piperine: 3.55 ± 0.30 mM, p < 0.01) and TG (Model: 1.41 ± 0.08 mM; Piperine: 0.94 ± 0.05 mM, p < 0.001), but also enhanced the glucose infusion rate in the hyperglycemic clamp experiment. Meanwhile, piperine improved glucose intolerance and insulin resistance in MSG obese mice. Piperine markedly decreased the total and differential white blood cell (WBC) count, the serum levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines such as galectin-3 (Gal-3) and interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M1-like polarization marker CD11c and Gal-3 in adipose tissues. The in vitro study showed that piperine inhibited LPS-stimulated polarization of RAW 264.7 cells toward the M1 phenotype. Conclusions Piperine served as an immunomodulator for the treatment of obesity-related diabetes through its anti-inflammatory effects, which might be achieved by inhibiting macrophages M1 polarization in adipose tissues.

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Anti-inflammatory effect of piperine ameliorates insulin resistance in monosodium glutamate–treated obese mice

10.21203/rs.3.rs-16723/v3 ◽

2020 ◽

Author(s):

Chaolong Liu ◽

Yanting Yuan ◽

Ji Zhou ◽

Ruixin Hu ◽

Lixia Ji ◽

...

Keyword(s):

Insulin Resistance ◽

Inflammatory Cytokines ◽

Monosodium Glutamate ◽

The Body ◽

Mrna Levels ◽

Obese Mice ◽

Adipose Tissues ◽

Newborn Mice ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Abstract Background: Metabolic inflammation is an essential event in obesity-induced diabetes and insulin resistance. In obesity, an increasing number of macrophages recruited into visceral adipose tissues undergo significant M1-like polarization, secreting variable amounts of pro-inflammatory cytokines and causing insulin resistance. Piperine has excellent anti-inflammatory activities and may be used in the treatment of a variety of inflammatory diseases. In this study, we investigated the effect of piperine on adipose tissue inflammation and insulin resistance in obese mice. Methods: Newborn mice were subcutaneously (s.c.) injected with monosodium glutamate (MSG) to establish a diabetes model. After 24 weeks, the MSG obese mice were divided into three groups and treated with piperine (40 mg/kg/day), metformin (150 mg/kg/day) and vehicle for 10 successive weeks, respectively. Results: The obesity model was successfully established, as the body weight, insulin resistance, fasting blood glucose (FBG) and dyslipidemia were significantly increased. The 10-week administration of piperine to the obese mice not only significantly decreased the elevated FBG (Model: 6.45 ± 0.41 mM; Piperine: 4.72 ± 0.44 mM, p<0.01), serum TC (Model: 5.66 ± 0.66 mM; Piperine: 3.55 ± 0.30 mM, p<0.01) and TG (Model: 1.41 ± 0.08 mM; Piperine: 0.94 ± 0.05 mM, p<0.001), but also enhanced the glucose infusion rate in the hyperglycemic clamp experiment. Meanwhile, piperine improved glucose intolerance and insulin resistance in MSG obese mice. Piperine markedly decreased the total and differential white blood cell (WBC) count, the serum levels of lipopolysaccharide (LPS) and pro-inflammatory cytokines such as galectin-3 (Gal-3) and interleukin-1β (IL-1β). Furthermore, piperine clearly down-regulated the mRNA levels of pro-inflammatory cytokines and the protein levels of M1-like polarization marker CD11c and Gal-3 in adipose tissues. The in vitro study showed that piperine inhibited LPS-stimulated polarization of RAW 264.7 cells toward the M1 phenotype. Conclusions: Piperine served as an immunomodulator for the treatment of obesity-related diabetes through its anti-inflammatory effects, which might be achieved by inhibiting macrophages M1 polarization in adipose tissues.

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