Impact of Exercise and Metabolic Disorders on Heat Shock Proteins and Vascular Inflammation

Noble, Earl G.; Shen, Garry X.

doi:10.1155/2012/836519

Cited by 45 publications

(35 citation statements)

References 176 publications

(206 reference statements)

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“…Previous studies reported that obesity and insulin resistance are associated with impaired expression of various components of the heat shock response, including members of DNAJ family [6,65,66]. It is also known that physical exercise induces the heat shock response and improves the clinical parameters associated with obesity and insulin resistance [13,67]. In our current investigation, we also showed that exercise induced the expression of HDAC4.…”

Section: Discussionsupporting

confidence: 76%

Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity

Dehbi¹

2013

Qatar Foundation Annual Research Forum Volume 2013 Issue 1

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Sedentary lifestyle and excessive energy intake are prominent contributors to obesity; a major risk factors for the development of insulin resistance, type 2 diabetes and cardiovascular diseases. Elucidating the molecular mechanisms underlying these chronic conditions is of relevant importance as it might lead to the identification of novel anti-obesity targets. The purpose of the current study is to investigate differentially expressed proteins between lean and obese subjects through a shot-gun quantitative proteomics approach using peripheral blood mononuclear cells (PBMCs) extracts as well as potential modulation of those proteins by physical exercise. Using this approach, a total of 47 proteins showed at least 1.5 fold change between lean and obese subjects. In obese, the proteomic profiling before and after 3 months of physical exercise showed differential expression of 38 proteins. Thrombospondin 1 (TSP1) was among the proteins that were upregulated in obese subjects and then decreased by physical exercise. Conversely, the histone deacetylase 4 (HDAC4) was downregulated in obese subjects and then induced by physical exercise. The proteomic data was further validated by qRT-PCR, Western blot and immunohistochemistry in both PBMCs and adipose tissue. We also showed that HDAC4 levels correlated positively with maximum oxygen consumption (V O2 Max ) but negatively with body mass index, percent body fat, and the inflammatory chemokine RANTES. In functional assays, our data indicated that ectopic expression of HDAC4 significantly impaired TNF-α-dependent activation of NF-κB, establishing thus a link between HDAC4 and regulation of the immune system. Together, the expression pattern of HDAC4 in obese subjects before and after physical exercise, its correlation with various physical, clinical and metabolic parameters along with its inhibitory effect on NF-κB are suggestive of a protective role of HDAC4 against obesity. HDAC4 could therefore represent a potential therapeutic target for the control and management of obesity and presumably insulin resistance.Citation: Abu-Farha M, Tiss A, Abubaker J, Khadir A, Al-Ghimlas F, et al. (2013) Proteomics Analysis of Human Obesity Reveals the Epigenetic Factor HDAC4 as a Potential Target for Obesity. PLoS ONE 8(9): e75342.

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Section: Discussionsupporting

confidence: 76%

Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity

Dehbi¹

2013

Qatar Foundation Annual Research Forum Volume 2013 Issue 1

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“…Exercise is also associated with transient elevations of Hsp expression, which may reduce inflammatory mediators (Noble and Shen 2012), suggesting that these proteins act as mediators of the effects of exercise on the immune function (Walsh et al 2001). Hsp70 is one of many DAMPs recognized by both TLR2 and TLR4 (Asea et al 2002).…”

Section: Discussionmentioning

confidence: 99%

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

Rodriguez‐Miguelez

Fernandez‐Gonzalo

Almar

et al. 2014

AGE

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This study assessed the effects of a resistance exercise training program on the inflammatory response associated with Toll-like receptor (TLR) 2 and TLR4 signaling pathways in senior participants. Twenty-six healthy subjects (age, 69.5±1.3) were randomized to a training (TG; n=16) or a control (CG; n=10) group. TG performed an 8-week resistance training program, while CG followed their daily routines. Peripheral blood mononuclear cells were isolated from blood samples obtained before and after the intervention, and levels of proteins involved in the TLR2, TLR4, and myeloid differentiation primary response gene 88 (MyD88)-dependent and MyD88-independent pathways were analyzed. The inflammatory status was evaluated through messenger RNA (mRNA) and protein content of interleukin (IL)-10 and tumor necrosis factor alpha (TNF-α) and plasma levels of C-reactive protein (CRP). After the 8-week resistance training, TLR2 and TLR4 protein expression was reduced in TG. MyD88, p65, phosphop38, TIR domain-containing adaptor inducing interferon (TRIF), IKKi/IKKε, phospho-interferon regulatory factor (IRF) 3, and phosho-IRF7 were also downregulated in TG after the intervention. The training program induced an increase of phospho-extracellular signal-regulated kinases 1 and 2 (ERK1/2) and Hsp70 and a reduction of Hsp60. While TNF-α mRNA and protein values remained unchanged in both TG and CG, IL-10 mRNA and protein content were upregulated in TG after the intervention. CRP values decreased in TG only. The increase in Hsp70 negatively correlated with TLR2 and TLR4 downregulation. These data suggest that resistance exercise may represent an effective tool to ameliorate the pro-inflammatory status of old participants through an attenuation of MyD88-dependent and MyD88-independent TLR2 and TLR4 signaling pathways.

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“…This was associated with decreases in Hsp70 levels in the FHL in response to exercise in both healthy and diabetic rats that were not observed in the soleus, which was not targeted by this training protocol. The process of muscle hypertrophy has been suggested to be preceded by muscle-damaging stress (Bischoff and Heintz 1994), indicating that an acute exercise overload may be considered stressful and may initiate the stress responses and production of inflammatory mediators (Malm 2001;Noble and Shen 2012;Silver et al 2012). However, some studies have shown that exercise training adaptations instead decreased inflammatory mediators and stress factors in skeletal muscle (Atalay et al 2004;Calle and Fernandez 2010;Molanouri Shamsi et al 2014).…”

Section: Discussionmentioning

confidence: 99%

Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats

Shamsi

Mahdavi

Quinn

et al. 2016

Cell Stress and Chaperones

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Impairment of adipose tissue and skeletal muscles accrued following type 1 diabetes is associated with protein misfolding and loss of adipose mass and skeletal muscle atrophy. Resistance training can maintain muscle mass by changing both inflammatory cytokines and stress factors in adipose tissue and skeletal muscle. The purpose of this study was to determine the effects of a 5-week ladder climbing resistance training program on the expression of Hsp70 and inflammatory cytokines in adipose tissue and fast-twitch flexor hallucis longus (FHL) and slow-twitch soleus muscles in healthy and streptozotocin-induced diabetic rats. Induction of diabetes reduced body mass, while resistance training preserved FHL muscle weight in diabetic rats without any changes in body mass. Diabetes increased Hsp70 protein content in skeletal muscles, adipose tissue, and serum. Hsp70 protein levels were decreased in normal and diabetic rats by resistance training in the FHL, but not soleus muscle. Furthermore, resistance training decreased inflammatory cytokines in FHL skeletal muscle.On the other hand, Hsp70 and inflammatory cytokine protein levels were increased by training in adipose tissue. Also, significant positive correlations between inflammatory cytokines in adipose tissue and skeletal muscles with Hsp70 protein levels were observed. In conclusion, we found that in diabetic rats, resistance training decreased inflammatory cytokines and Hsp70 protein levels in fast skeletal muscle, increased adipose tissue inflammatory cytokines and Hsp70, and preserved FHL muscle mass. These results suggest that resistance training can maintain skeletal muscle mass in diabetes by changing inflammatory cytokines and stress factors such as Hsp70 in skeletal muscle and adipose tissue.

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Impact of Exercise and Metabolic Disorders on Heat Shock Proteins and Vascular Inflammation

Cited by 45 publications

References 176 publications

Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity

Proteomics analysis of human obesity reveals the epigenetic factor HDAC4 as a potential target for obesity

Role of Toll-like receptor 2 and 4 signaling pathways on the inflammatory response to resistance training in elderly subjects

Effect of resistance exercise training on expression of Hsp70 and inflammatory cytokines in skeletal muscle and adipose tissue of STZ-induced diabetic rats

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