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 Metabolic markers and oxidative stress in children’s obesity pathogenesis

2020 ◽  
Vol 65 (1) ◽  
pp. 22-29
Author(s):  
O. V. Povarova ◽  
E. A. Gorodetskaya ◽  
E. I. Kalenikova ◽  
O. S. Medvedev
Keyword(s):  
Oxidative Stress ◽  
Adipose Tissue ◽  
Chronic Inflammation ◽  
Metabolic Disorders ◽  
Mineral Metabolism ◽  
Related Factors ◽  
Metabolic Markers ◽  
Hormonal Function ◽  
The Moment ◽  
Relationship Of

The article presents a modern view of obesity as a chronic inflammation of adipose tissue. Obesity is accompanied by metabolic changes in lipid, protein, carbohydrate, mineral metabolism and disorders in the hormonal function of adipose tissue as an endo- and paracrine organ. At the moment, there are searched the biochemical markers of metabolic disorders of obesity. The obesity-related factors (hyperglycemia, increased lipid levels, insulin resistance, chronic inflammation, hyperleptinemia, endothelial dysfunction, impaired respiratory function of mitochondria, minerals and microelements deficiency) form and increase oxidative stress making it an integral component of the pathogenesis of obesity and possible complications. Given the important role of Q10 coenzyme in antioxidant tissue protection, the authors discuss the relationship of obesity and metabolic disorders to the endogenous levels of Q10 coenzyme and its possible use for pharmacological correction.

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 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 Beneficial Effects of Alpha-Lipoic Acid on Hypertension, Visceral Obesity, UCP-1 Expression and Oxidative Stress in Zucker Diabetic Fatty Rats

Antioxidants ◽  
2019 ◽  
Vol 8 (12) ◽  
pp. 648 ◽  
Author(s):  
Adil El Midaoui ◽  
I. George Fantus ◽  
Ali Ait Boughrous ◽  
Réjean Couture
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Body Weight ◽  
Gastrocnemius Muscle ◽  
Antioxidant Properties ◽  
Visceral Obesity ◽  
Adipocyte Hypertrophy ◽  
Zdf Rats ◽  
Protein Staining ◽  
O2 Production

Evidence suggests that oxidative stress plays a major role in the development of metabolic syndrome. This study aims to investigate whether α-lipoic acid (LA), a potent antioxidant, could exert beneficial outcomes in Zucker diabetic fatty (ZDF) rats. Male 6-week-old ZDF rats and their lean counterparts (ZL) were fed for six weeks with a standard diet or a chow diet supplemented with LA (1 g/kg feed). At 12 weeks of age, ZDF rats exhibited an increase in systolic blood pressure, epididymal fat weight per body weight, hyperglycemia, hyperinsulinemia, insulin resistance (HOMA index), adipocyte hypertrophy and a rise in basal superoxide anion (O2•−) production in gastrocnemius muscle and a downregulation of epididymal uncoupled protein-1 (UCP-1) protein staining. Treatment with LA prevented the development of hypertension, the rise in whole body weight and O2•− production in gastrocnemius muscle, but failed to affect insulin resistance, hyperglycemia and hyperinsulinemia in ZDF rats. LA treatment resulted in a noticeable increase of pancreatic weight and a further adipocyte hypertrophy, along with a decrease in epididymal fat weight per body weight ratio associated with an upregulation of epididymal UCP-1 protein staining in ZDF rats. These findings suggest that LA was efficacious in preventing the development of hypertension, which could be related to its antioxidant properties. The anti-visceral obesity effect of LA appears to be mediated by its antioxidant properties and the induction of UCP-1 protein at the adipose tissue level in ZDF rats. Disorders of glucose metabolism appear, however, to be mediated by other unrelated mechanisms in this model of metabolic syndrome.

scholarly journals Codon-optimized FAM132b prevents diet-induced obesity by modulating adrenergic response and insulin action

2020 ◽  
Author(s):  
Zhengtang Qi ◽  
Jie Xia ◽  
Xiangli Xue ◽  
Wenbin Liu ◽  
Zhuochun Huang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Gene Transfer ◽  
Insulin Action ◽  
Metabolic Disorders ◽  
Codon Optimization ◽  
Whole Body ◽  
Therapeutic Effects ◽  
Glycemic Response ◽  
Adrenergic Response

AbstractFAM132b, also known as myonectin, has been identified as a myokine produced by exercise. It is a secreted protein precursor that belongs to the adipolin/erythroferrone family, and has hormone activity in circulation to regulate cellular iron homeostasis and lipid metabolism via unknown receptors. Here, adeno-associated viral vectors (AAV9) were engineered to induce overexpression of FAM132b with 2 codon mutations (A136T and P159A). Treatment of mice under high-fat diet feeding with FAM132b gene transfer resulted in marked reductions in body weight, fat depot, adipocytes size, glucose intolerance and insulin resistance. Moreover, FAM132b overproduction reduced glycemic response to epinephrine (EPI) in whole body and increased lipolytic response to EPI in adipose tissues. This adrenergic response of adipose tissue led to the result that gene transfer reduced glycogen utilization and increased fat consumption in skeletal muscle during exercise. FAM132b knockdown by shRNA significantly increased glycemic response to EPI in vivo and reduced adipocytes response to EPI and adipose tissue browning. Structural analysis suggested that FAM132b mutants delivered by AAV9 may form a weak bond with ADRB2, and potentially bind to insulin against insulin receptor by blocking the receptor binding sites on insulin B-chain. Our study underscores the potential of FAM132b gene therapy with codon optimization to treat obesity by modulating adrenergic response and interfering insulin action.SignificanceWe show here that AAV9-mediated expression of FAM132b with A136T and P159A is a safe and effective therapeutic strategy for improving glucose homeostasis. This is the first demonstration of a therapeutic effect on metabolic disorders in mice with FAM132b codon optimization. These therapeutic effects indicate that FAM132b gene transfer with selective codon mutants in vivo might be a valid therapy for diabetes that can be extended to other metabolic disorders.

The levels of adipocyte protein, a transporter of fatty acids, and adiponectin in the adolescents presenting with obesity and their relationship with the distribution of the adipose tissue

2014 ◽  
Vol 60 (2) ◽  
pp. 13-19
Author(s):  
P L Okorokov ◽  
O V Vasyukova ◽  
A V Vorontsov ◽  
A V Ilyin ◽  
V P Vladimirova ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Visceral Adipose Tissue ◽  
Metabolic Disorders ◽  
Adiponectin Level ◽  
Protein A ◽  
Visceral Obesity ◽  
Serum Adiponectin Level ◽  
Visceral Adipose ◽  
Subcutaneous Adipose

This study included 130 patients at the age of 14-17 years presenting with constitutional exogenous obesity (CEO) and 24 children without obesity (controls). The levels of adipocyte protein, a transporter of fatty acids (FABP4), in the sera of the adolescents with CEO were significantly higher than in the absence of obesity. They did not depend on the stage of puberty and differed in the children of different sex. The serum adiponectin level in the boys showed negative correlation with the amount of visceral adipose tissue and decreased progressively with the increase in the degree of obesity. The rise in the serum FABP4 level in the girls was associated with the increase in the amount of subcutaneous adipose tissue and positively correlated with the severity of obesity. Visceral obesity in the adolescents was accompanied by a variety of metabolic disorders while changes in the waist circumference did not reflect dynamics in the amount of visceral adipose tissue.

Comparative effects of N-acetyl-l-cysteine and ramipril on arterial hypertension, insulin resistance, and oxidative stress in chronically glucose-fed rats

2008 ◽  
Vol 86 (11) ◽  
pp. 752-760 ◽  
Author(s):  
Adil El Midaoui ◽  
Mahmoud Ali Ismael ◽  
Huogen Lu ◽  
I. George Fantus ◽  
Jacques de Champlain ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Plasma Levels ◽  
Superoxide Anion ◽  
Oxidase Activity ◽  
Therapeutic Effects ◽  
Superoxide Anion Production ◽  
Nadph Oxidase Activity

Beneficial effects of an antioxidant (N-acetyl-l-cysteine, NAC) and an angiotensin I-converting enzyme (ACE) inhibitor (ramipril) were assessed in a rat model of insulin resistance induced by 10% glucose feeding for 20 weeks. Treatments with NAC (2 g/kg per day) and ramipril (1 mg/kg per day) were initiated at 16 weeks in the drinking fluid. Systolic blood pressure, plasma levels of insulin and glucose, and insulin resistance were significantly higher in rats treated with glucose for 20 weeks. This was associated with a higher production of superoxide anion and NADPH oxidase activity in aorta and liver and with a marked reduction in protein expression of skeletal muscle insulin receptor substrate-1 (IRS-1) in the gastrocnemius muscle. NAC prevented all these alterations. Although ramipril also reversed high blood pressure, it had a lesser effect on insulin resistance (including IRS-1) and blocked superoxide anion production only in aorta. Ramipril, in contrast to NAC, did not reduce NADPH oxidase activity in aorta and liver or plasma levels of 4-hydroxynonenal and malondialdehyde. Results suggest that the inhibition of the oxidative stress in hypertensive and insulin-resistant states contributes to the therapeutic effects of NAC and ramipril. Whereas NAC exerts effective antioxidant activity in multiple tissues, ramipril appears to preferentially target the vasculature.

scholarly journals Inflammation Markers in Adipose Tissue and Cardiovascular Risk Reduction by Pomegranate Juice in Obesity Induced by a Hypercaloric Diet in Wistar Rats

Nutrients ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 2577
Author(s):  
Maria Monica Michicotl-Meneses ◽  
María del Rocío Thompson-Bonilla ◽  
César A. Reyes-López ◽  
Blanca Estela García-Pérez ◽  
Itzel I. López-Tenorio ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Density Lipoprotein ◽  
Pomegranate Juice ◽  
Lipoprotein Cholesterol ◽  
Therapeutic Effects ◽  
Inflammation Markers ◽  
Plasminogen Activator Inhibitor 1 ◽  
Cardiovascular Risk Reduction ◽  
Monocyte Chemoattractant Protein 1

Pomegranate juice (Punica granatum) has been used since ancient times in traditional medicine (Unani Medicine, Ayurveda); its main compounds are anthocyanins and ellagic acid, which have anti-inflammatory, antioxidant, hepatoprotective, and cardiovascular health effects. The objective was to evaluate the effect of pomegranate juice on inflammation, blood pressure, and vascular and physiological markers associated with obesity induced by a high-fat diet in a murine model. The results show that pomegranate juice reduces the concentration of low-density lipoprotein cholesterol (cLDL) 39% and increases the concentration of high-density lipoprotein cholesterol (cHDL) by 27%, leading to a 12%–18% decrease in the risk of cardiovascular diseases (CVD). In addition to reducing blood pressure by 24%, it also had an antiatherogenic effect by decreasing sE-selectin levels by 42%. On the other hand, the juice significantly increased adiponectin levels in adipose tissue, decreased levels of inflammation markers (tumor necrosis factor-α (TNF-α), plasminogen activator inhibitor-1 (PAI-1), interleukin-17A (IL-17A), interleukin-6 (IL-6), interleukin-1β (IL-1β)), and inhibited the monocyte chemoattractant protein-1 (MCP-1). Pomegranate juice requires clinical studies to prove its immunoregulatory and therapeutic effects on cardiovascular and atherogenic risks.

scholarly journals Deficiency of Angiotensin Type 2 Receptor Rescues Obesity But Not Hypertension Induced by Overexpression of Angiotensinogen in Adipose Tissue

Endocrinology ◽  
2008 ◽  
Vol 150 (3) ◽  
pp. 1421-1428 ◽  
Author(s):  
Laurent Yvan-Charvet ◽  
Florence Massiéra ◽  
Noël Lamandé ◽  
Gérard Ailhaud ◽  
Michèle Teboul ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adipose Tissue ◽  
Angiotensin Ii ◽  
Fat Mass ◽  
Lipogenic Gene Expression ◽  
Angiotensin Type 2 Receptor ◽  
Adipocyte Hypertrophy ◽  
Angiotensin Type

Increased angiotensinogen (AGT) production by white adipose tissue has been related to not only obesity but also hypertension. Several studies have highlighted the importance of the angiotensin II type 2 receptor (AT2) in the regulation of blood pressure and fat mass, but the relevance of this transporter in a physiopathological model of increased AGT production, as it occurs in obesity, has not yet been investigated. We used transgenic mice that display either a deletion of AT2 (AT2 KO), an overexpression of AGT (OVEX), or both compound mutants (KOVEX). Results demonstrated that adipocyte hypertrophy and increased lipogenic gene expression induced by adipose AGT overproduction was rescued by deletion of AT2. In line with AGT overexpression, KOVEX and OVEX mice have similar increased plasma AGT levels. However, KOVEX mice display a higher blood pressure than OVEX mice. In kidney, renin expression was clearly reduced in OVEX mice, and its expression was normalized in KOVEX mice. Taken together, we demonstrated that the loss of AT2 expression was sufficient to rescue obesity induced by adipose tissue AGT overexpression and confirmed the necessary role of AT2 for the onset of obesity in this model. Furthermore, despite a reduction of adipose mass in KOVEX, AT2 deficiency caused increased renin production, further worsening the hypertension caused by AGT overexpression. Angiotensin type 2 receptor shows antihypertensive function but promotes the angiotensin II-mediated fat mass enlargement.

Abstract 113: Glucose Metabolic Disorders in Aging-Associated Microglial NADPH Oxidase 2 Activation and Oxidative Damage of Cerebral Microvasculature and Neurons

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Li Geng ◽  
Jian-Mei Li
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Blood Pressure ◽  
Nadph Oxidase ◽  
Metabolic Disorders ◽  
Aging Brain ◽  
Ros Generation ◽  
Ros Production ◽  
The Brain

Aging has been recognised to be a major risk factor for the development of cardiovascular and neurodegenerative diseases and growing evidence suggests a role for oxidative stress. A Nox2-containing NADPH oxidase has been reported to be a major source of reactive oxygen species (ROS) generation in the vascular system and in the brain. However, the role of Nox2 enzyme in aging-related metabolic disorders and vascular neurodegeneration remains unclear. In this study, we used age-matched wild-type (WT) and Nox2-deficient (Nox2 -/- ) mice on a C57BL/6 background at young (3-4 month) and aging (20-24 month) to investigate the role of Nox2 in aging-related oxidative stress, metabolic disorders and cerebral vascular dysfunction. There was an aging-related increase in blood pressure in WT mice (126 mmHg for young and 148 mmHg for aging) (P<0.05); however the blood pressure was well maintained without significant change in Nox2 -/- aging mice. Compared to young WT mice, WT aging mice had significantly high levels of fasting serum insulin and this was accompanied with delayed clearance of glucose (P<0.05) indicating insulin resistance. In contrast, there was no indication of insulin resistance for Nox2 -/- aging mice. We then examined aging-related brain oxidative stress. Compared to WT young mice, there were significant increases (2.7±0.7 folds) in the levels of ROS production by WT aging brain tissue homogenates as detected by lucigenin-chemiluminescence and DHE fluorescence. Increased ROS production in WT aging brain was accompanied by a significant increase (1.8±0.3 folds) in the Nox2 expression detected mainly in the microglial cells (labelled by Iba-1) and decreases in brain capillaries (labelled by CD31) (2.4±0.8 folds) and neurons (labelled by Neu-N) (2.9±0.5 folds) (all P<0.05). Knockout of Nox2 abolished aging-associated increases in brain ROS production and significantly reduced the aging-related pathophysiological changes in the brain. In conclusion, aging-associated metabolic disorders play a crucial role in aging-associated Nox2 activation and vascular neurodegeneration. Nox2-containing NADPH oxidase represents a valuable therapeutic target for oxidative stress-related brain microvascular damage and neurodegeneration.

Sign in / Sign up

Export Citation Format

Share Document