Effects of resistance training and estrogen replacement on adipose tissue inflammation in ovariectomized rats

Estrogen deficiency is directly related to central obesity and low-grade inflammation. Hormonal replacement and exercise training are both able to decrease fat accumulation and inflammation in postmenopausal women. However, the efficiency of resistance training (RT) and estrogen replacement (ER) in minimizing adiposity and inflammation in the visceral adipose tissue (VAT) of ovariectomized (OVX) rats has not yet been elucidated. In this study, Sprague–Dawley rats were divided into the following 6 groups: sham-operated sedentary (Sham-Sed), OVX-Sed, Sham-RT, OVX-RT, OVX-Sed-ER, and OVX-RT-ER groups. ER was performed by implanting silastic capsules containing 17β-estradiol. For RT, the animals were required to climb a 1.1-m vertical ladder with conical flasks containing weights attached to their tails for 12 weeks. Histological analyses were used to evaluate morphological changes. Gene expression levels were determined by quantitative real-time reverse transcriptase polymerase chain reaction, and protein concentrations were determined using Multiplex/Luminex assays. Ovariectomy increased the body mass (BM), adipocyte area, and inflammation in the VAT, the latter of which was indicated by reduced interleukin-10 (48%) and increased tumor necrosis factor (TNF)-α concentration (∼3%). RT efficiently decreased BM, adipocyte area, and inflammation in the OVX groups. The combination of RT and ER decreased BM (19%) and the TNF-α concentration (18%) and increased the gene and protein expression levels of adiponectin (173% and 18%). These results indicate that RT and the combination of RT and ER are efficient strategies for reducing the BM and improving the inflammatory status of OVX rats.

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Effect of Resistance Training on NADPH Oxidase and Adiponectin in PVAT of OVX Rats

Exercise Science ◽

10.15857/ksep.2021.30.2.205 ◽

2021 ◽

Vol 30 (2) ◽

pp. 205-212

Author(s):

Erling Guo ◽

Jin-Hwan Yoon ◽

Wooyeon Jo ◽

Jaeho Jin ◽

Sang Ki Lee

Keyword(s):

Adipose Tissue ◽

Resistance Training ◽

Nadph Oxidase ◽

Abdominal Aorta ◽

Sham Group ◽

Ovariectomized Rats ◽

Sprague Dawley ◽

Perivascular Adipose Tissue ◽

Ovx Rats ◽

Sprague Dawley Rats

PURPOSE: Perivascular adipose tissue (PVAT) is a type of adipose tissue that surrounds vessels to provide anti-contractile effects. This study aimed to investigate the effect of resistance training on NADPH oxidase, adiponectin, and endothelial NOS (eNOS) expression in the abdominal aorta and PVAT of ovariectomized rats.METHODS: Sprague-Dawley rats at 20 weeks of age were divided into three groups: sham control (Sham, n=10), OVX-control (OVX_ Con, n=10), and OVX-resistance exercise (OVX_Rex, n=10). Resistance training was performed by climbing a ladder for 12 weeks. Western blotting was used to analyze target protein expression in the rat abdominal aorta and PVAT.RESULTS: NADPH oxidase (p67phox) expression was significantly higher in the OVX_Con group than in the sham group, but it was significantly decreased in the OVX_Rex group. The expression of adiponectin, AKT, and eNOS in both abdominal aorta and PVAT was significantly reduced in the OVX_Con group than in the Sham group, but it was improved in the OVX_Rex group.CONCLUSIONS:The results suggest that regular resistance training inhibits p67phox and increases adiponectin expression and phosphorylation of AKT and eNOS in abdominal aortic PVAT of ovariectomized rats.

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Puerarin Attenuates Obesity-Induced Inflammation and Dyslipidemia by Regulating Macrophages and TNF-Alpha in Obese Mice

Biomedicines ◽

10.3390/biomedicines10010175 ◽

2022 ◽

Vol 10 (1) ◽

pp. 175

Author(s):

Ji-Won Noh ◽

Hee-Kwon Yang ◽

Min-Soo Jun ◽

Byung-Cheol Lee

Keyword(s):

Adipose Tissue ◽

In Silico ◽

Tolerance Test ◽

Low Grade ◽

Adipocyte Size ◽

Metabolic Complications ◽

Immunological Mechanisms ◽

Tnf Α ◽

Test Serum

Obesity causes low-grade inflammation that results in dyslipidemia and insulin resistance. We evaluated the effect of puerarin on obesity and metabolic complications both in silico and in vivo and investigated the underlying immunological mechanisms. Twenty C57BL/6 mice were divided into four groups: normal chow, control (HFD), HFD + puerarin (PUE) 200 mg/kg, and HFD + atorvastatin (ATO) 10 mg/kg groups. We examined bodyweight, oral glucose tolerance test, serum insulin, oral fat tolerance test, serum lipids, and adipocyte size. We also analyzed the percentage of total, M1, and M2 adipose tissue macrophages (ATMs) and the expression of F4/80, tumor necrosis factor-α (TNF-α), C-C motif chemokine ligand 2 (CCL2), CCL4, CCL5, and C-X-C motif chemokine receptor 4. In silico, we identified the treatment-targeted genes of puerarin and simulated molecular docking with puerarin and TNF, M1, and M2 macrophages based on functionally enriched pathways. Puerarin did not significantly change bodyweight but significantly improved fat pad weight, adipocyte size, fat area in the liver, free fatty acids, triglycerides, total cholesterol, and HDL-cholesterol in vivo. In addition, puerarin significantly decreased the ATM population and TNF-α expression. Therefore, puerarin is a potential anti-obesity treatment based on its anti-inflammatory effects in adipose tissue.

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Lipopolysaccharide activates an innate immune system response in human adipose tissue in obesity and type 2 diabetes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00302.2006 ◽

2007 ◽

Vol 292 (3) ◽

pp. E740-E747 ◽

Cited By ~ 561

Author(s):

S. J. Creely ◽

P. G. McTernan ◽

C. M. Kusminski ◽

ff. M. Fisher ◽

N. F. Da Silva ◽

...

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Protein Expression ◽

Serum Insulin ◽

Human Adipose Tissue ◽

Innate Immune ◽

System Response ◽

Low Grade ◽

Tnf Α

Type 2 diabetes (T2DM) is associated with chronic low-grade inflammation. Adipose tissue (AT) may represent an important site of inflammation. 3T3-L1 studies have demonstrated that lipopolysaccharide (LPS) activates toll-like receptors (TLRs) to cause inflammation. For this study, we 1) examined activation of TLRs and adipocytokines by LPS in human abdominal subcutaneous (AbdSc) adipocytes, 2) examined blockade of NF-κB in human AbdSc adipocytes, 3) examined the innate immune pathway in AbdSc AT from lean, obese, and T2DM subjects, and 4) examined the association of circulating LPS in T2DM subjects. The findings showed that LPS increased TLR-2 protein expression twofold ( P < 0.05). Treatment of AbdSc adipocytes with LPS caused a significant increase in TNF-α and IL-6 secretion (IL-6, Control: 2.7 ± 0.5 vs. LPS: 4.8 ± 0.3 ng/ml; P < 0.001; TNF-α, Control: 1.0 ± 0.83 vs. LPS: 32.8 ± 6.23 pg/ml; P < 0.001). NF-κB inhibitor reduced IL-6 in AbdSc adipocytes (Control: 2.7 ± 0.5 vs. NF-κB inhibitor: 2.1 ± 0.4 ng/ml; P < 0.001). AbdSc AT protein expression for TLR-2, MyD88, TRAF6, and NF-κB was increased in T2DM patients ( P < 0.05), and TLR-2, TRAF-6, and NF-κB were increased in LPS-treated adipocytes ( P < 0.05). Circulating LPS was 76% higher in T2DM subjects compared with matched controls. LPS correlated with insulin in controls ( r = 0.678, P < 0.0001). Rosiglitazone (RSG) significantly reduced both fasting serum insulin levels (reduced by 51%, P = 0.0395) and serum LPS (reduced by 35%, P = 0.0139) in a subgroup of previously untreated T2DM patients. In summary, our results suggest that T2DM is associated with increased endotoxemia, with AT able to initiate an innate immune response. Thus, increased adiposity may increase proinflammatory cytokines and therefore contribute to the pathogenic risk of T2DM.

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Estrogen Inhibits Colon Polyp Formation by Reducing Angiogenesis in a Carcinogen-Induced Rat Model

International Journal of Endocrinology ◽

10.1155/2013/453898 ◽

2013 ◽

Vol 2013 ◽

pp. 1-7 ◽

Cited By ~ 6

Author(s):

Jia Yang ◽

Li-juan Xiong ◽

Fei Xu ◽

Xiang Zhao ◽

Bo Liu ◽

...

Keyword(s):

Rat Model ◽

Colon Polyp ◽

Ovariectomized Rats ◽

Nuclear Antigen ◽

Control Group ◽

Colon Polyps ◽

Estrogen Replacement ◽

Polyp Formation ◽

Ovx Rats ◽

Proliferating Cell

Objective.To study the effects of estrogen on colon polyp formation, proliferation, and angiogenesis on a rat model of colon cancer induced by dimethylhydrazine (DMH).Methods.Thirty-six female ovariectomized (OVX) rats were randomly divided into 3 groups: (I) control group (administrated with vehicles weekly), (II) DMH group (administrated with DMH weekly), and (III) DMH + E2group (administrated with DMH and 17β-estradiol weekly). The incidence, volumes, and multiplicity of colon polyps in each group were evaluated. The microvessel density (MVD), the expressions of Proliferating Cell Nuclear Antigen (PCNA), and the expressions of HIF-1αand VEGF in polyps were detected in each group.Results.Estrogen reduced the multiplicity, volumes, and the PCNA expressions of DMH-induced colon polyps. The MVD in DMH + E2group was significantly lower than that in DMH group. Estrogen treatment decreased the HIF-1αand VEGF expressions at both mRNA and protein level.Conclusion.Estrogen replacement was protective for ovariectomized rats from DMH-induced carcinogenesis, and one of the mechanisms for this was due to estrogen’s inhibitive effects on blood vessel formation by downregulating VEGF and HIF-1αexpressions.

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Betaine reduces the expression of inflammatory adipokines caused by hypoxia in human adipocytes

British Journal Of Nutrition ◽

10.1017/s0007114512000888 ◽

2012 ◽

Vol 109 (1) ◽

pp. 43-49 ◽

Cited By ~ 18

Author(s):

K. Olli ◽

S. Lahtinen ◽

N. Rautonen ◽

K. Tiihonen

Keyword(s):

Adipose Tissue ◽

Inflammatory Markers ◽

Mrna Level ◽

Low Grade ◽

Human Adipocytes ◽

Low Oxygen ◽

Hypoxic Conditions ◽

Tnf Α ◽

Oxygen Conditions ◽

Low Grade Inflammation

Obesity is characterised by a state of chronic low-grade inflammation and the elevated circulating and tissue levels of inflammatory markers, including inflammation-related adipokines, released from white adipose tissue. The expression and release of these adipokines generally rises as the adipose tissue expands and hypoxic conditions start to develop within the tissue. Here, the effect of betaine, a trimethylglycine having a biological role as an osmolyte and a methyl donor, on the expression of inflammation-related markers was tested in human adipocytes under hypoxia. Differentiated adipocytes were cultivated under low (1 %) oxygen tension for 8–20 h. The expression of different adipokines, including IL-6, leptin, PPARγ, TNF-α and adiponectin, was measured by quantitative PCR by determining the relative mRNA level from the adipocytes. Hypoxia, in general, led to a decrease in the expression of PPARγ mRNA in human adipocytes, whereas the expression levels of leptin and IL-6 mRNA were substantially increased by hypoxia. The cultivation of adipocytes under hypoxia also led to a reduction in the expression of TNF-α mRNA. The results showed that hypoxia increased the relative quantification of leptin gene transcription, and that betaine (250 μmol/l) reduced this effect, caused by low oxygen conditions. Under hypoxia, betaine also reduced the mRNA level of the pro-inflammatory markers IL-6 and TNF-α. These results demonstrate that the extensive changes in the expression of inflammation-related adipokines in human adipocytes caused by hypoxia can be diminished by the presence of physiologically relevant concentrations of betaine.

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Influence of miRNA-30a-5p on Pulmonary Fibrosis in Mice with Streptococcus pneumoniae Infection through Regulation of Autophagy by Beclin-1

BioMed Research International ◽

10.1155/2021/9963700 ◽

2021 ◽

Vol 2021 ◽

pp. 1-8

Author(s):

Hanyu Liu ◽

Yabo Li ◽

Yingdong Zou ◽

Xingzong Zhang ◽

Xiongfei Shi ◽

...

Keyword(s):

Streptococcus Pneumoniae ◽

Pulmonary Fibrosis ◽

Protein Level ◽

Beclin 1 ◽

Enzyme Linked Immunosorbent Assay ◽

Mrna Levels ◽

Pulmonary Tissue ◽

Expression Levels ◽

Tnf Α ◽

Gene And Protein Expression

The study is aimed at observing the influence of microribonucleic acid- (miRNA-) 30a-50p on the pulmonary fibrosis in mice with Streptococcus pneumoniae infection through the regulation of autophagy by Beclin-1. Specific pathogen-free mice were instilled with Streptococcus pneumoniae through the trachea to establish the pulmonary fibrosis model. Then, they were divided into the miRNA-30a-50p mimics group (mimics group, n = 10 ) and miRNA-30a-5p inhibitors group (inhibitors group, n = 10 ), with the control group ( n = 10 ) also set. Pulmonary tissue wet weight/dry weight (W/D) was detected. The content of tumor necrosis factor-α (TNF-α), interleukin- (IL-) 6, and myeloperoxidase (MPO) was determined using enzyme-linked immunosorbent assay (ELISA). Besides, the changes in the pulmonary function index dynamic lung compliance (Cdyn), plateau pressure (Pplat), and peak airway pressure (Ppeak) were monitored, and the gene and protein expression levels were measured via quantitative PCR (qPCR) and Western blotting. The expression level of miRNA-30a-5p was substantially raised in the mimics group ( p < 0.05 ), but extremely low in the inhibitors group ( p < 0.05 ). The mimics group had obviously raised levels of serum aminotransferase (AST), glutamic-pyruvic transaminase (GPT), alkaline phosphatase (ALP), and pulmonary tissue W/D ( p < 0.05 ). Additionally, the expression levels of TNF-α, IL-6, and MPO were notably elevated in the mimics group, while their expression levels showed the opposite conditions in the inhibitors group ( p < 0.05 ). According to the HE staining results, the inhibitors group had arranged orderly cells, while the mimics group exhibited lung injury, pulmonary edema, severe inflammatory response, and alveolar congestion. In the inhibitors group, Cdyn was remarkably elevated, but Pplat and Ppeak declined considerably ( p < 0.05 ). Besides, the inhibitors group exhibited elevated messenger RNA (mRNA) levels of Beclin-1 and LC3, lowered mRNA levels of α-SMA and p62, a raised protein level of Beclin-1, and a markedly decreased protein level of p62 ( p < 0.05 ). Silencing miRNA-30a-5p expression can promote the expression of Beclin-1 to accelerate the occurrence of autophagy, thereby treating pulmonary fibrosis in mice with Streptococcus pneumoniae infection.

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Obesity and inflammation: the effects of weight loss

Nutrition Research Reviews ◽

10.1017/s0954422408138732 ◽

2008 ◽

Vol 21 (2) ◽

pp. 117-133 ◽

Cited By ~ 200

Author(s):

L. Kirsty Forsythe ◽

Julie M. W. Wallace ◽

M. Barbara E. Livingstone

Keyword(s):

Physical Activity ◽

Weight Loss ◽

Inflammatory Marker ◽

Present Review ◽

Low Grade ◽

Surgical Interventions ◽

Inflammatory Status ◽

Tnf Α ◽

Induce Weight Loss ◽

Inflammatory Profile

Following the discovery of TNF-α and leptin as secretory products of adipocytes in the early 1990s, subsequent obesity research focused on the new functional role of adipose tissue, as an active endocrine organ. Many more inflammatory peptides have been linked to adiposity, which ultimately characterised obesity as a state of low-grade systemic inflammation, or ‘metaflammation’ which may link obesity to its co-morbidities. The aim of the present review is to examine the effects of weight loss on inflammation in overweight and obese, but otherwise healthy, populations. Studies were broadly classified into four types (diet, physical activity, diet and physical activity combined, and surgical interventions) and discussed according to the method used to induce weight loss. All studies measured at least one obesity-related inflammatory marker (ORIM). The overall finding from the present review is that weight loss does improve inflammation in terms of both the inflammatory (C-reactive protein, TNF-α, IL-6 and leptin) and anti-inflammatory (adiponectin) ORIM. Within this, the greatest improvements in ORIM are observed in studies achieving a weight loss of at least 10 %. However, a number of methodological issues have been identified as potential limitations within the literature including the sex and age of subjects, sample size, study duration and the assessment of body composition. In conclusion, although a period of weight loss per se is capable of reversing the unfavourable inflammatory profile evident in the obese state, further studies are required to determine the time needed, in which a reduced weight is maintained, in order to benefit from improved inflammatory status long term.

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TNF-α Represses β-Klotho Expression and Impairs FGF21 Action in Adipose Cells: Involvement of JNK1 in the FGF21 Pathway

Endocrinology ◽

10.1210/en.2012-1193 ◽

2012 ◽

Vol 153 (9) ◽

pp. 4238-4245 ◽

Cited By ~ 118

Author(s):

Julieta Díaz-Delfín ◽

Elayne Hondares ◽

Roser Iglesias ◽

Marta Giralt ◽

Carme Caelles ◽

...

Keyword(s):

Adipose Tissue ◽

High Fat Diet ◽

Mouse Embryonic Fibroblast ◽

Fibroblast Growth Factor 21 ◽

High Fat ◽

Fgf Receptor ◽

Inflammatory Status ◽

Tnf Α

Fibroblast growth factor 21 (FGF21) is a member of the FGF family that reduces glycemia and ameliorates insulin resistance. Adipose tissue is a main target of FGF21 action. Obesity is associated with a chronic proinflammatory state. Here, we analyzed the role of proinflammatory signals in the FGF21 pathway in adipocytes, evaluating the effects of TNF-α on β-Klotho and FGF receptor-1 expression and FGF21 action in adipocytes. We also determined the effects of rosiglitazone on β-Klotho and FGF receptor-1 expression in models of proinflammatory signal induction in vitro and in vivo (high-fat diet-induced obesity). Because c-Jun NH2-terminal kinase 1 (JNK1) serves as a sensing juncture for inflammatory status, we also evaluated the involvement of JNK1 in the FGF21 pathway. TNF-α repressed β-Klotho expression and impaired FGF21 action in adipocytes. Rosiglitazone prevented the reduction in β-Klotho expression elicited by TNF-α. Moreover, β-Klotho levels were reduced in adipose tissue from high-fat diet-induced obese mice, whereas rosiglitazone restored β-Klotho to near-normal levels. β-Klotho expression was increased in white fat from JNK1−/− mice. The absence of JNK1 increased the responsiveness of mouse embryonic fibroblast-derived adipocytes and brown adipocytes to FGF21. In conclusion, we show that proinflammatory signaling impairs β-Klotho expression and FGF21 responsiveness in adipocytes. We also show that JNK1 activity is involved in modulating FGF21 effects in adipocytes. The impairment in the FGF21 response machinery in adipocytes and the reduction in FGF21 action in response to proinflammatory signals may play important roles in metabolic alterations in obesity and other diseases associated with enhanced inflammation.

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Estrogen replacement restores flow-induced vasodilation in coronary arterioles of aged and ovariectomized rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00178.2009 ◽

2009 ◽

Vol 297 (6) ◽

pp. R1713-R1723 ◽

Cited By ~ 43

Author(s):

Amanda J. LeBlanc ◽

Rafael Reyes ◽

Lori S. Kang ◽

Robert A. Dailey ◽

John N. Stallone ◽

...

Keyword(s):

Nitric Oxide ◽

Ovarian Hormones ◽

Female Rats ◽

Ovariectomized Rats ◽

Estrogen Replacement ◽

Cvd Risk ◽

Young Females ◽

Ovx Rats ◽

Coronary Arterioles ◽

Reduced Flow

The risk for cardiovascular disease (CVD) increases with advancing age; however, the age at which CVD risk increases significantly is delayed by more than a decade in women compared with men. This cardioprotection, which women experience until menopause, is presumably due to the presence of ovarian hormones, in particular, estrogen. The purpose of this study was to determine how age and ovarian hormones affect flow-induced vasodilation in the coronary resistance vasculature. Coronary arterioles were isolated from young (6 mo), middle-aged (14 mo), and old (24 mo) intact, ovariectomized (OVX), and ovariectomized + estrogen replaced (OVE) female Fischer-344 rats to assess flow-induced vasodilation. Advancing age impaired flow-induced dilation of coronary arterioles (young: 50 ± 4 vs. old: 34 ± 6; % relaxation). Ovariectomy reduced flow-induced dilation in arterioles from young females, and estrogen replacement restored vasodilation to flow. In aged females, flow-induced vasodilation of arterioles was unaltered by OVX; however, estrogen replacement improved flow-induced dilation by ∼160%. The contribution of nitric oxide (NO) to flow-induced dilation, assessed by nitric oxide synthase (NOS) inhibition with NG-nitro-l-arginine methyl ester (l-NAME), declined with age. l-NAME did not alter flow-induced vasodilation in arterioles from OVX rats, regardless of age. In contrast, l-NAME reduced flow-induced vasodilation of arterioles from estrogen-replaced rats at all ages. These findings indicate that the age-induced decline of flow-induced, NO-mediated dilation in coronary arterioles of female rats is related, in part, to a loss of ovarian estrogen, and estrogen supplementation can improve flow-induced dilation, even at an advanced age.

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