Impact of hepatic HSP72 on insulin signaling

Kitano, Sayaka; Kondo, Tatsuya; Matsuyama, Rina; Ono, Kaoru; Goto, Rieko; Takaki, Yuki; Hanatani, Satoko; Sakaguchi, Masaji; Igata, Motoyuki; Kawashima, Junji; Motoshima, Hiroyuki; Matsumura, Takeshi; Kai, Hirofumi; Araki, Eiichi

doi:10.1152/ajpendo.00215.2018

Cited by 15 publications

(18 citation statements)

References 42 publications

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“…Furthermore, silencing of HSP72 was shown to increase JNK activity while silencing of JNK decreased TNF-α, IL-6 and IL-8 levels, and apoptosis, while elevating cell viability. Reports have suggested that the knockout of HSP72, a natural inhibitor of JNK leads to an increase in JNK activity (Park et al 2001 ; Kitano et al 2019 ) while patients with severe COPD have been noted to exhibit upregulated levels of JNK in their adipose tissues (Tkacova et al 2011 ). Consistently, patients with COPD displayed increased numbers of positive cells for phosphorylated JNK in epithelial cells (Eurlings et al 2017 ).…”

Section: Discussionmentioning

confidence: 99%

“…Overexpression of HSP72 reportedly inhibits the production of lipopolysaccharide (LPS)-induced inflammatory cytokines resulting in a decrease in inflammatory injury in murine immune cells (Muralidharan et al 2014 ). Moreover, COPD patients have been observed exhibit both upregulated activity and phosphorylation of c-Jun N-terminal kinase (JNK) (Eurlings et al 2017 ); knockdown of HSP72 has been reported to elevate the activity and phosphorylation of JNK (Kitano et al 2019 ), which may represent a potential mechanism by which HSP72 protects against inflammatory injury in the lung. However, the exact mechanism by which baicalin exerts its protective role against COPD is yet to be elucidated.…”

Section: Introductionmentioning

confidence: 99%

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Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway

Hao

Shi

et al. 2021

Mol Med

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Background Chronic obstructive pulmonary disease (COPD) is characterized by airway obstruction and progressive lung inflammation. As the primary ingredient of a traditional Chinese medical herb, Baicalin has been previously shown to possess anti-inflammatory abilities. Thus, the current study aimed to elucidate the mechanism by which baicalin alleviates COPD. Methods Baicalin was adopted to treat cigarette smoke in extract-exposed MLE-12 cells after which cell viability and apoptosis were determined. The production of tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), IL-8 were determined by enzyme-linked immunoassay. A COPD mouse model was constructed via exposure to cigarette smoke and lipopolysaccharide, baicalin treatment. Lung function and inflammatory cell infiltration were determined and the production of Muc5AC, TNF-α, IL-6, IL-8 in the bronchoalveolar lavage fluid (BALF) was assayed by ELISA. The effect of HSP72 and JNK on COPD following treatment with baicalin was assessed both in vivo and in vitro by conducting loss- and gain- function experiments. Results Baicalin improved lung function evidenced by reduction in inflammatory cell infiltration and Muc5AC, TNF-α, IL-6 and IL-8 levels observed in BALF in mice. Baicalin was further observed to elevate cell viability while inhibited apoptosis and TNF-α, IL-6 and IL-8 levels in MLE-12 cells. Baicalin treatment increased HSP72 expression, while its depletion reversed the effect of baicalin on COPD. HSP72 inhibited the activation of JNK, while JNK activation was found to inhibit the effect of baicalin on COPD. Conclusions Baicalin upregulated the expression of HSP72, resulting in the inhibition of JNK signaling activation, which ultimately alleviates COPD.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway

Hao

Shi

et al. 2021

Mol Med

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“…Previous studies have clearly shown that insulin sensitivity could be improved by HSP72 induction via heat treatment (42°C for 30 min), pharmacologic intervention, and transgenic overexpression [23,38,39]. On the other hand, mice with HSP72 deletion were prone to be obese and glucose intolerant [40], further supporting the role of HSP72 in metabolic regulation.…”

Section: Discussionmentioning

confidence: 85%

Joint Effects of Heat Stress and PM2.5 Exposure on Glucose Metabolism and Hepatic Insulin Signaling

Gu¹,

Cai²,

Zhong³

et al. 2021

Preprint

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Background: Heatwave events are occurring more frequently, accompanied by a significant increase in the ambient concentration of fine particulate matter (PM2.5). Epidemiological studies have suggested that heat stress or PM2.5 exposure would impair glucose homeostasis and insulin sensitivity, but the combined effect and the exact mechanisms are not well understood.Methods: C57BL/6 mice were randomly divided into filtered air (FA), fine particulate matter (PM) group, filtered air combined with heat stress (FH) group, and fine particulate matter combined with heat stress (PH) group for a 4-week PM2.5 exposure, followed by a 2-week heat stress exposure, via a whole-body exposure system. Systemic glucose homeostasis, insulin sensitivity, and circulating inflammatory cytokines were examined. HSP72 expression and insulin signaling in the liver were measured.Results: Glucose tolerance and insulin sensitivity were impaired in response to heat stress, accompanied by lessened hepatic GLUT2 expression and inhibited insulin signaling pathway. No synergistic effects of heat stress and PM2.5 exposure on glucose homeostasis were observed, while heat-upregulated HSP72 expression was attenuated with accumulated TNF-α induced by further PM2.5 exposure.Conclusions: Heat stress combined with PM2.5 exposure induced TNF-α, which could inhibit heat-elevated hepatic HSP72 expression. Elevated circulating TNF-α impaired hepatic insulin signaling and GLUT2 expression. Then, glucose homeostasis was perturbed, and insulin action was impaired.

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“…Our previous reports suggest that HSP72 induction by geranylgeranylacetone (GGA) or heat shock (HS) + mild electrical stimulation (MES) attenuates metabolic abnormalities such as glucose intolerance, insulin resistance, chronic inflammation, enhanced hepatic gluconeogenesis, and steatosis in mouse models of diabetes as well as in patients with metabolic syndrome and type 2 diabetes ( 6 , 7 , 8 ). The introduction of HSP72 specifically in the liver of whole-body HSP72 knockout mice by lentivirus resulted in the amelioration of whole-body glucose homeostasis and inflammation as well as hepatic gluconeogenesis and steatosis ( 9 ). Therefore, the hepatic role of HSP72 should be more precisely investigated.…”

Section: Introductionmentioning

confidence: 99%

Activation of heat shock response improves biomarkers of NAFLD in patients with metabolic diseases

Kondo

Miyakawa

Kitano

et al. 2021

Endocrine Connections

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Nonalcoholic fatty liver disease (NAFLD) is often accompanied by metabolic disorders such as metabolic syndrome and type 2 diabetes (T2DM). Heat shock response (HSR) is one of the most important homeostatic abilities, but is deteriorated by chronic metabolic insults. Heat shock (HS) with appropriate mild electrical stimulation (MES) activates HSR, and improves metabolic abnormalities including insulin resistance, hyperglycemia and inflammation in metabolic disorders. To analyze the effects of HS + MES treatment on NAFLD biomarkers, three cohorts including healthy men (2 times/week, n=10), patients with metabolic syndrome (4 times/week, n=40), and patients with T2DM (n=100; 4 times/week (n=40) and 2, 4, 7 times/week (n=20 each)) treated with HS + MES were retrospectively analyzed. The healthy subjects showed no significant alterations in NAFLD biomarkers after the treatment. In patients with metabolic syndrome, many of the NAFLD steatosis markers, including fatty liver index, NAFLD-liver fat score, liver/spleen ratio and hepatic steatosis index and NAFLD fibrosis marker, aspartate aminotransferase/alanine aminotransferase (AST/ALT) ratio, were improved upon the treatment. In patients with T2DM, all investigated NAFLD steatosis markers were improved and NAFLD fibrosis markers such as the AST/ALT ratio, fibrosis-4 index and NAFLD-fibrosis score were improved upon the treatment. Thus, HS + MES, a physical intervention, may become a novel treatment strategy for NAFLD as well as metabolic disorders.

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Impact of hepatic HSP72 on insulin signaling

Cited by 15 publications

References 42 publications

Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway

Baicalin alleviates chronic obstructive pulmonary disease through regulation of HSP72-mediated JNK pathway

Joint Effects of Heat Stress and PM2.5 Exposure on Glucose Metabolism and Hepatic Insulin Signaling

Activation of heat shock response improves biomarkers of NAFLD in patients with metabolic diseases

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