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Decreased HSF1 levels in obese patients correlated with NAFLD progression

Many obese adults who underwent bariatric surgery showed decreased HSF1 levels, indicating a progression in nonalcoholic fatty liver disease, according to new study data.

“The interconnection between obesity, inflammation and HSP70 pathways encompass a much more complex network that operates at the gene regulatory level,” the researchers wrote. “[We investigated] whether HSP70 pathways could be impaired in the liver and adipose tissue of NAFLD patients, thus allowing JNK-triggered inflammatory signals to reach metabolic tissues.”

Ninety-five patients with class 3 obesity who underwent bariatric surgery were included in the study. All patients underwent intraoperative liver biopsy and were divided into three groups: steatosis (28.4%), steatohepatitis (40%) and steatohepatitis with fibrosis (31.6%). Clinical, plasma and NAFLD scoring data from all the patients were evaluated, as well as HSP70, HSF1 and JNKs levels. Furthermore, liver biopsies from 22 patients with NAFLD also were analyzed for HSP70 and JNK proteins.

Results showed that HSP70 (HSP72, HSP73) proteins from adipose tissue found in the patients with NAFLD were inversely correlated with NAFLD progression (Spearman rank correlation=–0.934; P<.05) and decreased among the patients with NASH compared with the steatosis groups (P<.05). This decrease correlated with the suppressed HSF1 in adipose tissue from the same group of patients.

In the hepatic tissue from the liver biopsies, HSP70 protein levels decreased as NAFLD progressed (Spearman rank correlation=–0.456; P<.05). Among the hepatic tissue in patients with NAFLD, JNK1 and p-JNK1 were “reciprocally enhanced” with HSP70 levels; JNK2 was not found in the liver tissue.

“In the present work, the heat shock protein biochemical pathway, whose activity is powerfully cytoprotective and anti-inflammatory, was found to be depressed and negatively correlated with NAFLD progression in both the liver and adipose tissue of NAFLD patients,” the researchers concluded. “These observations may have an important diagnostic value for severely obese and NAFLD patients because the ‘HSP70 status’ may be assessed in the circulating blood of human patients using a small blood drop.”

Disclosure: The researchers report no relevant financial disclosures.