Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression.


OBJECTIVES To evaluate whether reduced activity of the anti-inflammatory HSP70 pathway correlates with nonalcoholic fatty liver disease (NAFLD) progression and with markers of oxidative stress because obesity activates inflammatory JNKs, whereas HSP70 exerts the opposite effect. METHODS Adult obese patients (N = 95) undergoing bariatric surgery were divided into steatosis (ST), steatohepatitis (SH), and fibrosis (SH+F) groups. The levels of HSP70, its major transcription factor, HSF1, and JNKs were assessed by immunoblotting hepatic and visceral adipose tissue; data were confirmed by immunohistochemistry. Plasma biochemistry (lipids, HbA1c , HOMA, hepatic enzymes, and redox markers) was also evaluated. RESULTS In both liver and adipose tissue, decreased HSP70 levels, paralleled by similar reductions in HSF1 and reduced plasma antioxidant enzyme activities, correlated with insulin resistance and with NAFLD progression (expression levels were as follows: ST > SH > SH + F). The immunohistochemistry results suggested Kupffer cells as a site of HSP70 inhibition. Conversely, JNK1 content and phosphorylation increased. CONCLUSIONS Decreased HSF1 levels in the liver and fat of obese patients correlated with impairment of HSP70 in an NAFLD stage-dependent manner. This impairment may affect HSP70-dependent anti-inflammation, with consequent oxidative stress and insulin resistance in advanced stages of NAFLD. Possible causal effects of fat cell senescence are discussed.

DOI: 10.1002/oby.20919
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@article{Naso2015ObesityDT, title={Obesity depresses the anti-inflammatory HSP70 pathway, contributing to NAFLD progression.}, author={F{\'a}bio Cangeri Di Naso and Rossana Rosa Porto and Henrique Sarubbi Fillmann and Lucas S Maggioni and Alexandre Vontobel Padoin and Rafael Jacques Ramos and Cl{\'a}udio Cor{\'a} Mottin and Aline Bittencourt and N. Marroni and Paulo Ivo Homem de Bittencourt}, journal={Obesity}, year={2015}, volume={23 1}, pages={120-9} }