RAGE influences obesity in mice

Leuner, Beatrice; Max, M. C.; Thamm, K.; Kausler, C.; Yakobus, Yuliana; Bierhaus, Angelika; Sel, Saadettin; Hofmann, Britt; Silber, Rolf-Edgar; Simm, Andreas; Naß, Norbert

doi:10.1007/s00391-011-0279-x

Cited by 38 publications

(13 citation statements)

References 28 publications

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“…The findings are consistent with those of Monden et al (28) where RAGE null mice fed HFD (20% of total calories from cocoa butter and 0.15% from cholesterol) were protected from diet-induced obesity and insulin resistance and confirm the finding that RAGE contributes to regulation of adipocyte hypertrophy. In contrast, Leuner et al (29) reported that RAGE null mice fed an HFD (60% of calories from fat) displayed greater obesity versus the WT cohort. However, Leuner et al did not test the specific effects of RAGE expression in hematopoietic cells or the effects of RAGE antagonism.…”

Section: Discussionmentioning

confidence: 92%

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

et al. 2014

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In mammals, changes in the metabolic state, including obesity, fasting, cold challenge, and high-fat diets (HFDs), activate complex immune responses. In many strains of rodents, HFDs induce a rapid systemic inflammatory response and lead to obesity. Little is known about the molecular signals required for HFD-induced phenotypes. We studied the function of the receptor for advanced glycation end products (RAGE) in the development of phenotypes associated with high-fat feeding in mice. RAGE is highly expressed on immune cells, including macrophages. We found that high-fat feeding induced expression of RAGE ligand HMGB1 and carboxymethyllysine-advanced glycation end product epitopes in liver and adipose tissue. Genetic deficiency of RAGE prevented the effects of HFD on energy expenditure, weight gain, adipose tissue inflammation, and insulin resistance. RAGE deficiency had no effect on genetic forms of obesity caused by impaired melanocortin signaling. Hematopoietic deficiency of RAGE or treatment with soluble RAGE partially protected against peripheral HFD-induced inflammation and weight gain. These findings demonstrate that high-fat feeding induces peripheral inflammation and weight gain in a RAGE-dependent manner, providing a foothold in the pathways that regulate diet-induced obesity and offering the potential for therapeutic intervention.

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Section: Discussionmentioning

confidence: 92%

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

et al. 2014

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“…This implication is mostly related to its capacity to interact with advanced glycation end products (AGE) [51]. AGE can signal through RAGE to activate oxidative stress and inflammation and finally interfere with insulin-signaling pathways in adipocytes to decrease insulin sensitivity [52], [53].…”

Section: Discussionmentioning

confidence: 99%

Soluble HMGB1 Is a Novel Adipokine Stimulating IL-6 Secretion through RAGE Receptor in SW872 Preadipocyte Cell Line: Contribution to Chronic Inflammation in Fat Tissue

Nativel¹,

Marimoutou

Thon-Hon³

et al. 2013

PLoS ONE

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Low-grade inflammation (LGI) is a central phenomenon in the genesis of obesity and insulin-resistance characterized by IL-6 in human serum. Whereas this LGI was initially thought to be mainly attributed to macrophage activation, it is now known that pre-adipocytes and adipocytes secrete several adipokines including IL-6 and participate to LGI and associated pathologies. In macrophages, HMGB1 is a nuclear yet secreted protein and acts as a cytokine to drive the production of inflammatory molecules through RAGE and TLR2/4. In this paper we tested the secretion of HMGB1 and the auto- and paracrine contribution to fat inflammation using the human preadipocyte cell line SW872 as a model. We showed that 1) human SW872 secreted actively HMGB1, 2) IL-6 production was positively linked to high levels of secreted HMGB1, 3) recombinant HMGB1 boosted IL-6 expression and this effect was mediated by the receptor RAGE and did not involve TLR2 or TLR4. These results suggest that HMGB1 is a major adipokine contributing to LGI implementation and maintenance, and can be considered as a target to develop news therapeutics in LGI associated pathologies such as obesity and type II diabetes.

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“…( 51 , 72 , 79 ) Glyoxal, MDA and hydroxynonenal (HNE) are products of peroxidation lipids. ( 72 , 80 , 81 ) Table 1 outlines the various classes of AGEs. ( 73 , 82 , 83 ) It is now known that endogenous AGEs contribute to aging, CVD, kidney disease, diabetes, Alzheimer’s disease (AD), cataracts, autoimmune diseases, allergies, endocrine disorders and gastrointestinal disturbances.…”

Section: Advanced Glycation End-productsmentioning

confidence: 99%

Advanced glycation end-products: modifiable environmental factors profoundly mediate insulin resistance

Ottum

Mistry

2015

J. Clin. Biochem. Nutr.

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Advanced glycation end-products are toxic by-products of metabolism and are also acquired from high-temperature processed foods. They promote oxidative damage to proteins, lipids and nucleotides. Aging and chronic diseases are strongly associated with markers for oxidative stress, especially advanced glycation end-products, and resistance to peripheral insulin-mediated glucose uptake. Modifiable environmental factors including high levels of refined and simple carbohydrate diets, hypercaloric diets and sedentary lifestyles drive endogenous formation of advanced glycation end-products via accumulation of highly reactive glycolysis intermediates and activation of the polyol/aldose reductase pathway producing high intracellular fructose. High advanced glycation end-products overwhelm innate defenses of enzymes and receptor-mediated endocytosis and promote cell damage via the pro-inflammatory and pro-oxidant receptor for advanced glycation end-products. Oxidative stress disturbs cell signal transduction, especially insulin-mediated metabolic responses. Here we review emerging evidence that restriction of dietary advanced glycation end-products significantly reduces total systemic load and insulin resistance in animals and humans in diabetes, polycystic ovary syndrome, healthy populations and dementia. Of clinical importance, this insulin sensitizing effect is independent of physical activity, caloric intake and adiposity level.

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RAGE influences obesity in mice

Abstract: These data suggest that RAGE is involved in the development of obesity and insulin resistance.

Cited by 38 publications

References 28 publications

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

RAGE Regulates the Metabolic and Inflammatory Response to High-Fat Feeding in Mice

Soluble HMGB1 Is a Novel Adipokine Stimulating IL-6 Secretion through RAGE Receptor in SW872 Preadipocyte Cell Line: Contribution to Chronic Inflammation in Fat Tissue

Advanced glycation end-products: modifiable environmental factors profoundly mediate insulin resistance

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