scholarly journals Attenuation of obesity and related metabolic disorders by the individual or combination treatment with IL-2/anti-IL-2 complex and hyperbaric oxygen

2018 ◽  
Author(s):  
Eun-Jeong Choi ◽  
Hyung-Ran Kim ◽  
Kie Jeong-Hae ◽  
Byung-In Moon ◽  
Ju-Young Seoh
Keyword(s):  
Adipose Tissue ◽  
Hyperbaric Oxygen ◽  
Combination Treatment ◽  
Metabolic Disorders ◽  
The Body ◽  
Low Grade ◽  
Control Groups ◽  
Adipocyte Hypertrophy ◽  
The Individual ◽  
Tissue Browning

AbstractObesity is the disease accumulating excessive fat in the body. The prevalence of obesity and related metabolic disorders is increasing every year worldwide. Immunologically, obesity is a chronic low-grade inflammatory state with the increase of M1 macrophages and decrease of regulatory T cells (Tregs). IL-2/anti-IL-2 complex (IL-2C) and hyperbaric oxygen (HBO) are known to expand Tregs in vivo and suppress inflammation. Therefore, in this study, IL-2C and HBO were investigated for the preventive effect of obesity and related metabolic disorders. Male C57BL/6 mice were fed with a high-fat diet (HFD) for 16 weeks, and counterparts were fed with a low-fat diet (LFD). At the end of the experiment, the body weight gain and impaired glucose metabolism, elevated levels of insulin and total cholesterol induced by HFD were improved by the individual or combination treatment with Il-2C and HBO. Histological examination of the epididymal white adipose tissue showed adipocyte hypertrophy and many crown-like structures in the HFD control groups. In addition, the liver showed the progression of non-alcoholic fatty liver disease (NAFLD) in the HFD control groups, but it was significantly improved by the individual or combination treatment with IL-2C and HBO.As for the underlying mechanism, inflammation induced by obesity was decreased, and HIF-1α expression by adipocyte hypertrophy was also reduced by the individual or combination treatment with IL-2C and HBO. In addition, adipose tissue browning was activated in brown and inguinal adipose tissue, and the expression of UCP-1 involved in the thermogenesis was increased by the individual or combination treatment with IL-2C and HBO. Overall, these results suggested that IL-2C and HBO might be a new promising immunotherapy for the treatment of obesity and related metabolic disorders by regulation of inflammation and activation of adipose tissue browning.

Abstract 1125: Mulberry Leaf Ameliorates The Production Of Adipocytokines By Inhibiting Oxidative Stress In White Adipose Tissue In db/db Mice

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Masayuki Sugimoto ◽  
Hidenori Arai ◽  
Yukinori Tamura ◽  
Toshinori Murayama ◽  
Koh Ono ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Metabolic Disorders ◽  
The Body ◽  
Mulberry Leaf ◽  
The Metabolic Syndrome ◽  
Pparγ Agonist ◽  
Tnf Α

Mulberry leaf (ML) is commonly used to feed silkworms. Previous study showed that ML ameliorates atherosclerosis. However, its mechanism is not completely understood. Because dysregulated production of adipocytokines is involved in the development of the metabolic syndrome and cardiovascular disease, we examined the effect of ML on the production of adipocytokines and metabolic disorders related to the metabolic syndrome, and compared its effect with that of a PPARγ agonist, pioglitazone (Pio). By treating obese diabetic db/db mice with ML, Pio, and their combination, we investigated the mechanism by which they improve metabolic disorders. In this study, db/+m (lean control) and db/db mice were fed a standard diet with or without 3% (w/w) ML and/or 0.01% (w/w) Pio for 12 weeks from 9 weeks of age. At the end of the experiment we found that ML decreased plasma glucose and triglyceride by 32% and 30%, respectively. Interestingly, administration of ML in addition to Pio showed additive effects; further 40% and 30% reduction in glucose and triglyceride compared with Pio treatment, respectively. Moreover, administration of ML in addition to Pio suppressed the body weight increase by Pio treatment and reduced visceral/subcutaneous fat ratio by 20% compared with control db/db mice. Importantly, ML treatment increased expression of adiponectin in white adipose tissue (WAT) by 40%, which was only found in db/db mice, not in control db/+m mice. Combination of ML and Pio increased plasma adiponectin concentrations by 25% and its expression in WAT by 17% compared with Pio alone. In contrast, ML decreased expression of TNF-α and MCP-1 by 25% and 20%, respectively, and the addition of Pio resulted in a further decrease of these cytokines by about 45%. To study the mechanism, we examined the role of oxidative stress. ML decreased the amount of lipid peroxides by 43% and the expression of NADPH oxidase subunits in WAT, which was consistent with the results of TNF-α and MCP-1. Thus our results indicate that ML ameliorates adipocytokine dysregulation by inhibiting oxidative stress in WAT of obese mice, and that ML may have a potential for the treatment of the metabolic syndrome as well as reducing adverse effects of Pio.

scholarly journals Pharmacological myeloperoxidase (MPO) inhibition in an obese/hypertensive mouse model attenuates obesity and liver damage, but not cardiac remodeling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Arnold Piek ◽  
Debby P. Y. Koonen ◽  
Elisabeth-Maria Schouten ◽  
Eva L. Lindtstedt ◽  
Erik Michaëlsson ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mouse Model ◽  
The Body ◽  
Low Grade ◽  
Protective Effects ◽  
Positive Effects ◽  
Low Fat Diet ◽  
Multiple Organs ◽  
Cardiac Phenotype ◽  
Obesity Hypertension

AbstractLifestyle factors are important drivers of chronic diseases, including cardiovascular syndromes, with low grade inflammation as a central player. Attenuating myeloperoxidase (MPO) activity, an inflammatory enzyme associated with obesity, hypertension and heart failure, could have protective effects on multiple organs. Herein, the effects of the novel oral available MPO inhibitor AZM198 were studied in an obese/hypertensive mouse model which displays a cardiac phenotype. Eight week old male C57BL6/J mice received 16 weeks of high fat diet (HFD) combined with angiotensin II (AngII) infusion during the last 4 weeks, with low fat diet and saline infusion as control. Treated animals showed therapeutic AZM198 levels (2.1 µM), corresponding to 95% MPO inhibition. AZM198 reduced elevated circulating MPO levels in HFD/AngII mice to normal values. Independent of food intake, bodyweight increase and fat accumulation were attenuated by AZM198, alongside with reduced visceral adipose tissue (VAT) inflammation and attenuated severity of nonalcoholic steatohepatitis. The HFD/AngII perturbation caused impaired cardiac relaxation and contraction, and increased cardiac hypertrophy and fibrosis. AZM198 treatment did, however, not improve these cardiac parameters. Thus, AZM198 had positive effects on the main lipid controlling tissues in the body, namely adipose tissue and liver. This did, however, not directly result in improved cardiac function.

scholarly journals CD90 serves as differential modulator of subcutaneous and visceral adipose-derived stem cells by regulating AKT activation that influences adipose tissue and metabolic homeostasis

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Zhenzhen Pan ◽  
Zixin Zhou ◽  
Huiying Zhang ◽  
Hui Zhao ◽  
Peixuan Song ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Adipogenic Differentiation ◽  
Clonal Expansion ◽  
S Phase ◽  
Adipose Derived Stem Cells ◽  
Akt Activation ◽  
Adipocyte Hypertrophy ◽  
Mitotic Clonal Expansion ◽  
Visceral Adipose

Abstract Background White adipose tissue includes subcutaneous and visceral adipose tissue (SAT and VAT) with different metabolic features. SAT protects from metabolic disorders, while VAT promotes them. The proliferative and adipogenic potentials of adipose-derived stem cells (ADSCs) are critical for maintaining adipose tissue homeostasis through driving adipocyte hyperplasia and inhibiting pathological hypertrophy. However, it remains to be elucidated the critical molecules that regulate different potentials of subcutaneous and visceral ADSCs (S-ADSCs, V-ADSCs) and mediate distinct metabolic properties of SAT and VAT. CD90 is a glycosylphosphatidylinositol-anchored protein on various cells, which is also expressed on ADSCs. However, its expression patterns and differential regulation on S-ADSCs and V-ADSCs remain unclear. Methods S-ADSCs and V-ADSCs were detected for CD90 expression. Proliferation, colony formation, cell cycle, mitotic clonal expansion, and adipogenic differentiation were assayed in S-ADSCs, V-ADSCs, or CD90-silenced S-ADSCs. Glucose tolerance test and adipocyte hypertrophy were examined in mice after silencing of CD90 in SAT. CD90 expression and its association with CyclinD1 and Leptin were analyzed in adipose tissue from mice and humans. Regulation of AKT by CD90 was detected using a co-transfection system. Results Compared with V-ADSCs, S-ADSCs expressed high level of CD90 and showed increases in proliferation, mitotic clonal expansion, and adipogenic differentiation, together with AKT activation and G1-S phase transition. CD90 silencing inhibited AKT activation and S phase entry, thereby curbing proliferation and mitotic clonal expansion of S-ADSCs. In vivo CD90 silencing in SAT inhibited S-ADSC proliferation, which caused adipocyte hypertrophy and glucose intolerance in mice. Furthermore, CD90 was highly expressed in SAT rather than in VAT in human and mouse, which had positive correlation with CyclinD1 but negative correlation with Leptin. CD90 promoted AKT activation through recruiting its pleckstrin homology domain to plasma membrane. Conclusions CD90 is differentially expressed on S-ADSCs and V-ADSCs, and plays critical roles in ADSC proliferation, mitotic clonal expansion, and hemostasis of adipose tissue and metabolism. These findings identify CD90 as a crucial modulator of S-ADSCs and V-ADSCs to mediate distinct metabolic features of SAT and VAT, thus proposing CD90 as a valuable biomarker or target for evaluating ADSC potentials, monitoring or treating obesity-associated metabolic disorders.

scholarly journals NLRP3 Inflammasome Activation in Adipose Tissues and Its Implications on Metabolic Diseases

2020 ◽  
Vol 21 (11) ◽  
pp. 4184 ◽  
Author(s):  
Kelvin Ka-Lok Wu ◽  
Samson Wing-Ming Cheung ◽  
Kenneth King-Yip Cheng
Keyword(s):  
Adipose Tissue ◽  
Nlrp3 Inflammasome ◽  
Metabolic Disorders ◽  
Immune Cell ◽  
Diabetic Patients ◽  
Inflammasome Activation ◽  
Low Grade ◽  
Adipose Tissues ◽  
Adipose Tissue Dysfunction ◽  
Nlrp3 Inflammasome Activation

Adipose tissue is an active endocrine and immune organ that controls systemic immunometabolism via multiple pathways. Diverse immune cell populations reside in adipose tissue, and their composition and immune responses vary with nutritional and environmental conditions. Adipose tissue dysfunction, characterized by sterile low-grade chronic inflammation and excessive immune cell infiltration, is a hallmark of obesity, as well as an important link to cardiometabolic diseases. Amongst the pro-inflammatory factors secreted by the dysfunctional adipose tissue, interleukin (IL)-1β, induced by the NLR family pyrin domain-containing 3 (NLRP3) inflammasome, not only impairs peripheral insulin sensitivity, but it also interferes with the endocrine and immune functions of adipose tissue in a paracrine manner. Human studies indicated that NLRP3 activity in adipose tissues positively correlates with obesity and its metabolic complications, and treatment with the IL-1β antibody improves glycaemia control in type 2 diabetic patients. In mouse models, genetic or pharmacological inhibition of NLRP3 activation pathways or IL-1β prevents adipose tissue dysfunction, including inflammation, fibrosis, defective lipid handling and adipogenesis, which in turn alleviates obesity and its related metabolic disorders. In this review, we summarize both the negative and positive regulators of NLRP3 inflammasome activation, and its pathophysiological consequences on immunometabolism. We also discuss the potential therapeutic approaches to targeting adipose tissue inflammasome for the treatment of obesity and its related metabolic disorders.

scholarly journals Enhanced nutritionally induced adipose tissue development in mice with stromelysin-1 gene inactivation

2003 ◽  
Vol 89 (04) ◽  
pp. 696-704 ◽  
Author(s):  
Erik Maquoi ◽  
Diego Demeulemeester ◽  
Gabor Vörös ◽  
Désire Collen ◽  
H. Lijnen
Keyword(s):  
Adipose Tissue ◽  
Research Society ◽  
The Body ◽  
Tissue Development ◽  
Cholesterol Levels ◽  
Fat Deposits ◽  
Adipose Tissue Development ◽  
Adipocyte Hypertrophy ◽  
Deficient Mice

SummaryTo investigate a potential role of stromelysin-1 (MMP-3) in development of adipose tissue, 5 week old male MMP-3 deficient mice (MMP-3-/-) and wild-type (MMP-3+/+) controls were kept on a high fat diet (HFD) for 15 weeks. MMP-3-/- mice were hyperphagic and gained more weight than the MMP-3+/+ mice. At the time of sacrifice, the body weight of the MMP-3-/- mice was significantly higher than that of the MMP-3+/+ mice, as was the weight of the isolated subcutaneous (SC) and gonadal (GON) fat deposits. Significant adipocyte hypertrophy was observed in the GON but not in the SC adipose tissue of MMP-3-/- mice. Fasting plasma glucose and cholesterol levels were comparable in both genotypes, whereas triglyceride levels were significantly lower in MMP-3-/- mice. Staining with an endothelial cell specific lectin revealed a significantly higher blood vessel density and larger total stained area in the GON adipose tissues of MMP-3-/- mice. Thus, in a murine model of nutritionally induced obesity, MMP-3 impairs adipose tissue development, possibly by affecting food intake and/or adipose tissue-related angiogenesis.Theme paper: Part of this paper was originally presented at the joint meetings of the 16th International Congress of the International Society of Fibrinolysis and Proteolysis (ISFP) and the 17th International Fibrinogen Workshop of the International Fibrinogen Research Society (IFRS) held in Munich, Germany, September, 2002.

scholarly journals Differential effects of EPA and DHA on plasma and adipose tissue lipid mediators: the ComparED study

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Cécile Vors ◽  
Fabiana Piscitelli ◽  
Roberta Verde ◽  
Sofia Laforest ◽  
Janie Allaire ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Plasma Levels ◽  
Corn Oil ◽  
Lipid Mediators ◽  
High Dose ◽  
Low Grade ◽  
Double Blind ◽  
Epa And Dha ◽  
Anti Inflammatory ◽  
The Individual

AbstractOxylipins and endocannabinoids (eCBs) both belong to superclasses of lipid mediators with potent inflammation modulatory activities. The adipose tissue (AT) plays a key role in metabolic syndrome-related inflammation, via altered adipocyte physiology, infiltrated macrophages and altered profile of eCBs. We previously reported that DHA is more potent than EPA at modulating systemic inflammation, but the underlying mechanisms remain unclear. The objective of this study was to compare the individual effect of high-dose DHA and of EPA on circulating lipid mediators, i.e. plasma oxylipins and eCBs, and AT-related inflammation. In a randomized double-blind crossover trial, 154 volunteers with abdominal obesity and low-grade inflammation were subjected to three 10-wk supplementation phases: 1- EPA (2.7 g/d); 2- DHA (2.7 g/d); 3- corn oil (control), each separated by a 9-wk washout. Supplements were provided as re-esterified triacylglycerols. Profiling of plasma oxylipins and eCBs was performed on 58 subjects after each phase. Abdominal subcutaneous AT biopsies were also obtained from 13 individuals after each phase. Plasma DHA-, EPA-, arachidonic acid-derived oxylipins were analyzed by LC-MS. eCBs and some of their bioactive congeners were analyzed in plasma and AT by LC-APCI-MS. Adipocyte diameter was determined by histological analysis and AT macrophage infiltration was quantified by double immunofluorescence. Compared with EPA, DHA increased plasma levels of hydroxy-docosahexaenoic acids (7-, 11-, 14-, 4-, 17-HDOHE; P < 0.0001) and palmitoylethanolamide (PEA; P = 0.04). Compared with DHA, EPA led to higher plasma level of hydroxy-eicosapentaenoic acids (12-, 15-, 5-HEPE; P < 0.0001). In the AT, EPA increased the level of oleoylethanolamide (OEA; P = 0.01) compared with DHA, but no other difference was observed between treatments in adipose eCBs and eCB-related lipids. DHA and EPA did not differentially modify adipocyte size distributions (P > 0.50) and proportions of M1-type and M2-type macrophages (P > 0.30). In conclusion, increased plasma levels of anti-inflammatory DHA-derived oxylipins and plasma PEA may be responsible, at least to some extent, for the more potent anti-inflammatory effects of DHA compared with EPA observed in the ComparED study. Conversely, subcutaneous AT does not seem to be involved in explaining such differences between EPA and DHA.

scholarly journals Effects of the Angiotensin Receptor Blocker Olmesartan on Adipocyte Hypertrophy and Function in Mice with Metabolic Disorders

2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Akinobu Maeda ◽  
Kouichi Tamura ◽  
Hiromichi Wakui ◽  
Masato Ohsawa ◽  
Kengo Azushima ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Blood Pressure ◽  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Visceral Obesity ◽  
Pleiotropic Effects ◽  
Stress Axis ◽  
Therapeutic Effects ◽  
Kkay Mice ◽  
Adipocyte Hypertrophy

In the present study, we examined the therapeutic effects of olmesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders with visceral obesity, with a focus on an olmesartan effect on the adipose tissue. Olmesartan treatment (3 mg/kg per day) for 4 weeks significantly lowered systolic blood pressure but did not affect body weight during the study period in KKAy mice. However, there were three interesting findings possibly related to the pleiotropic effects of olmesartan on adipose tissue in KKAy mice: (1) an inhibitory effect on adipocyte hypertrophy, (2) a suppressive effect on IL-6 gene expression, and (3) an ameliorating effect on oxidative stress. On the other hand, olmesartan exerted no evident influence on the adipose tissue expression of AT1R-associated protein (ATRAP), which is a molecule interacting with AT1R so as to inhibit pathological AT1R activation and is suggested to be an emerging molecular target in metabolic disorders with visceral obesity. Collectively, these results suggest that the blood pressure lowering effect of olmesartan in KKAy mice is associated with an improvement in adipocyte, including suppression of adipocyte hypertrophy and inhibition of the adipose IL-6-oxidative stress axis. Further study is needed to clarify the functional role of adipose ATRAP in the pleiotropic effects of olmesartan.

scholarly journals Linking obesogenic dysregulation to prostate cancer progression

2015 ◽  
Vol 4 (4) ◽  
pp. R68-R80 ◽  
Author(s):  
Renea A Taylor ◽  
Jennifer Lo ◽  
Natasha Ascui ◽  
Matthew J Watt
Keyword(s):  
Prostate Cancer ◽  
Adipose Tissue ◽  
Cancer Progression ◽  
Prostate Gland ◽  
The Body ◽  
Endocrine Function ◽  
Low Grade ◽  
Prostate Cancer Progression ◽  
Cancer Aggressiveness ◽  
Increased Risk

The global epidemic of obesity is closely linked to the development of serious co-morbidities, including many forms of cancer. Epidemiological evidence consistently shows that obesity is associated with a similar or mildly increased incidence of prostate cancer but, more prominently, an increased risk for aggressive prostate cancer and prostate cancer-specific mortality. Studies in mice demonstrate that obesity induced by high-fat feeding increases prostate cancer progression; however, the mechanisms underpinning this relationship remain incompletely understood. Adipose tissue expansion in obesity leads to local tissue dysfunction and is associated with low-grade inflammation, alterations in endocrine function and changes in lipolysis that result in increased delivery of fatty acids to tissues of the body. The human prostate gland is covered anteriorly by the prominent peri-prostatic adipose tissue and laterally by smaller adipose tissue depots that lie directly adjacent to the prostatic surface. We discuss how the close association between dysfunctional adipose tissue and prostate epithelial cells might result in bi-directional communication to cause increased prostate cancer aggressiveness and progression. However, the literature indicates that several ‘mainstream’ hypotheses regarding obesity-related drivers of prostate cancer progression are not yet supported by a solid evidence base and, in particular, are not supported by experiments using human tissue. Understanding the links between obesity and prostate cancer will have major implications for the health policy for men with prostate cancer and the development of new therapeutic or preventative strategies.

scholarly journals Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

2021 ◽  
Vol 12 ◽  
Author(s):  
Christine Bourgeois ◽  
Jennifer Gorwood ◽  
Anaelle Olivo ◽  
Laura Le Pelletier ◽  
Jacqueline Capeau ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hiv Infection ◽  
Systemic Inflammation ◽  
Immune Cells ◽  
The Body ◽  
Whole Body ◽  
Viral Reservoir ◽  
Low Grade ◽  
Endocrine Activity ◽  
Inflammatory Signals

White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity. Several of AT’s intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. In obesity, the concomitant pro-inflammatory signals produced by immune cells, adipocytes and adipose stem cells help to drive local inflammation in a vicious circle. Although the secretion of adipokines by AT is a prime contributor to systemic inflammation, the lipotoxicity associated with AT dysfunction might also be involved and could affect distant organs. In HIV-infected patients, the AT is targeted by both HIV infection and antiretroviral therapy (ART). During the primary phase of infection, the virus targets AT directly (by infecting AT CD4 T cells) and indirectly (via viral protein release, inflammatory signals, and gut disruption). The initiation of ART drastically changes the picture: ART reduces viral load, restores (at least partially) the CD4 T cell count, and dampens inflammatory processes on the whole-body level but also within the AT. However, ART induces AT dysfunction and metabolic side effects, which are highly dependent on the individual molecules and the combination used. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA and induce oxidative stress and adipocyte death. Protease inhibitors predominantly affect metabolic pathways (affecting adipogenesis and adipocyte homeostasis) resulting in insulin resistance. Recently marketed integrase strand transfer inhibitors induce both adipocyte adipogenesis, hypertrophy and fibrosis. It is challenging to distinguish between the respective effects of viral persistence, persistent immune defects and ART toxicity on the inflammatory profile present in ART-controlled HIV-infected patients. The host metabolic status, the size of the pre-established viral reservoir, the quality of the immune restoration, and the natural ageing with associated comorbidities may mitigate and/or reinforce the contribution of antiretrovirals (ARVs) toxicity to the development of low-grade inflammation in HIV-infected patients. Protecting AT functions appears highly relevant in ART-controlled HIV-infected patients. It requires lifestyle habits improvement in the absence of effective anti-inflammatory treatment. Besides, reducing ART toxicities remains a crucial therapeutic goal.

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