Adipose tissue inflammation and cancer cachexia: the role of steroid hormones

AbstractAdipose tissue inflammation plays a role in the etiology of many chronic diseases, and has been the focus of much attention in the context of obesity and metabolic syndrome. Similarly, during cancer cachexia, a syndrome that markedly increases cancer-associated morbidity and mortality, local adipose inflammation is reported in animal models and in patients, potentially contributing to the chronic systemic inflammation that constitutes the hallmark of this condition. We discuss, on the basis of information generated by obesity-related studies, the possible relation between adipose tissue inflammation and compromised steroid hormone secretion and action in cachexia.

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Adipocyte-Derived Lactate Potentiates Obesity-Evoked Adipose Macrophage Inflammation

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.079 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A40-A41

Author(s):

Xiaoyan Hannah Hui ◽

Tianshi Feng

Keyword(s):

Adipose Tissue ◽

Lactate Level ◽

Macrophage Polarization ◽

Lactate Production ◽

Physiological Role ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Adipose Inflammation

Abstract Introduction: Obesity is characterized by mobilization of macrophage inflammation, which represents the major events of obesity-associated adipose tissue inflammation. . On the other hand, lactate accumulation in adipose tissue long been observed. However, whether elevation of lactate plays an essential role in adipose inflammation is not known. In this study, we sought to examine the intermediary role of lactate in macrophage polarization and adipose inflammation upon obesity. Method: Lactate level and activity of lactate dehydrogense (LDH), the key enzyme of lactate production, were measured by biochemical assays. Adipocyte- and macrophage- specific Ldha knock out mice were constructed by cre-LoxP system to study the physiological role of lactate in diet induced obesity. Macrophage polarization and inflammation were examined by western blotting and Q-PCR. Results: Lactate and LDH activity were selectively upregulated in adipose tissues of obese mice. Adipocyte-, but not macrophage-selective deletion of LDHA, led to a significant improvement of adipose inflammation and metabolic dysfunctions. In vitro experiments showed that the lactate promoted M1 polarization through direct interation and inhibition of the PHD2, which subsequently stabilizes HIF-1alpha. In addition, a positive correlation between adipose lactate level and adipose tissue inflammation was found in obese patients. Conclusion: In obese condition, increased production of lactate from adipocytes enhances adipose tissue inflammation by promoting the proinflammatory polarization of adipose macrophages.

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Adipose tissue inflammation and cancer cachexia: Possible role of nuclear transcription factors

Cytokine ◽

10.1016/j.cyto.2011.10.008 ◽

2012 ◽

Vol 57 (1) ◽

pp. 9-16 ◽

Cited By ~ 51

Author(s):

M.L. Batista ◽

S.B. Peres ◽

M.E. McDonald ◽

P.S.M. Alcantara ◽

M. Olivan ◽

...

Keyword(s):

Adipose Tissue ◽

Transcription Factors ◽

Cancer Cachexia ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation

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Adipose tissue inflammation and metabolic syndrome. The proactive role of probiotics

European Journal of Nutrition ◽

10.1007/s00394-018-1790-2 ◽

2018 ◽

Vol 58 (1) ◽

pp. 27-43 ◽

Cited By ~ 26

Author(s):

Sebastian Torres ◽

Emanuel Fabersani ◽

Antonela Marquez ◽

Paola Gauffin-Cano

Keyword(s):

Metabolic Syndrome ◽

Adipose Tissue ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Proactive Role

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Adipose tissue inflammation and metabolic dysfunction: a clinical perspective

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci-2013-0032 ◽

2013 ◽

Vol 15 (1) ◽

Cited By ~ 2

Author(s):

Charmaine S. Tam ◽

Leanne M. Redman

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Low Grade ◽

Metabolic Dysfunction ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Proinflammatory Mediators ◽

Low Grade Inflammation

AbstractObesity is characterized by a state of chronic low-grade inflammation due to increased immune cells, specifically infiltrated macrophages into adipose tissue, which in turn secrete a range of proinflammatory mediators. This nonselective low-grade inflammation of adipose tissue is systemic in nature and can impair insulin signaling pathways, thus, increasing the risk of developing insulin resistance and type 2 diabetes. The aim of this review is to provide an update on clinical studies examining the role of adipose tissue in the development of obesity-associated complications in humans. We will discuss adipose tissue inflammation during different scenarios of energy imbalance and metabolic dysfunction including obesity and overfeeding, weight loss by calorie restriction or bariatric surgery, and conditions of insulin resistance (diabetes, polycystic ovarian syndrome).

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The role of glucose-6-phosphate dehydrogenase in adipose tissue inflammation in obesity

Adipocyte ◽

10.1080/21623945.2017.1288321 ◽

2017 ◽

Vol 6 (2) ◽

pp. 147-153 ◽

Cited By ~ 10

Author(s):

Yoon Jeong Park ◽

Sung Sik Choe ◽

Jee Hyung Sohn ◽

Jae Bum Kim

Keyword(s):

Adipose Tissue ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Glucose 6 Phosphate Dehydrogenase

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The role of uncoupling protein 2 in macrophages and its impact on obesity-induced adipose tissue inflammation and insulin resistance

Journal of Biological Chemistry ◽

10.1074/jbc.ra120.014868 ◽

2020 ◽

Vol 295 (51) ◽

pp. 17535-17548

Author(s):

Xanthe A. M. H. van Dierendonck ◽

Tiphaine Sancerni ◽

Marie-Clotilde Alves-Guerra ◽

Rinke Stienstra

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Macrophage Activation ◽

Uncoupling Protein ◽

Uncoupling Protein 2 ◽

Adipose Tissue Inflammation ◽

Tissue Inflammation ◽

Obesity And Diabetes ◽

Adipose Tissue Macrophages

The development of a chronic, low-grade inflammation originating from adipose tissue in obese subjects is widely recognized to induce insulin resistance, leading to the development of type 2 diabetes. The adipose tissue microenvironment drives specific metabolic reprogramming of adipose tissue macrophages, contributing to the induction of tissue inflammation. Uncoupling protein 2 (UCP2), a mitochondrial anion carrier, is thought to separately modulate inflammatory and metabolic processes in macrophages and is up-regulated in macrophages in the context of obesity and diabetes. Here, we investigate the role of UCP2 in macrophage activation in the context of obesity-induced adipose tissue inflammation and insulin resistance. Using a myeloid-specific knockout of UCP2 (Ucp2ΔLysM), we found that UCP2 deficiency significantly increases glycolysis and oxidative respiration, both unstimulated and after inflammatory conditions. Strikingly, fatty acid loading abolished the metabolic differences between Ucp2ΔLysM macrophages and their floxed controls. Furthermore, Ucp2ΔLysM macrophages show attenuated pro-inflammatory responses toward Toll-like receptor-2 and -4 stimulation. To test the relevance of macrophage-specific Ucp2 deletion in vivo, Ucp2ΔLysM and Ucp2fl/fl mice were rendered obese and insulin resistant through high-fat feeding. Although no differences in adipose tissue inflammation or insulin resistance was found between the two genotypes, adipose tissue macrophages isolated from diet-induced obese Ucp2ΔLysM mice showed decreased TNFα secretion after ex vivo lipopolysaccharide stimulation compared with their Ucp2fl/fl littermates. Together, these results demonstrate that although UCP2 regulates both metabolism and the inflammatory response of macrophages, its activity is not crucial in shaping macrophage activation in the adipose tissue during obesity-induced insulin resistance.

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