Fetuin-A mRNA expression is elevated in NASH compared with NAFL patients

Abstract

Fetuin-A is a pro-inflammatory protein expressed by hepatocytes. Its course in morbidly obese patients with NAFLD (non-alcoholic fatty liver disease) following weight loss by BAS (bariatric surgery) has not been fully elucidated yet. In the present study, we prospectively examined the effects of weight loss on various metabolic factors at 4 weeks and 6 months after surgery. Blood and liver tissues were retrieved from 108 morbidly obese NAFLD patients before/during BAS, and 50 of these individuals met the criteria for NASH (non-alcoholic steatohepatitis). Fetuin-A expression was measured by qPCR (quantitative real-time PCR), Western blotting and immunohistochemistry. Hepatocyte apoptosis was quantified via M30 (caspase-cleaved cytokeratin-18 fragments). Plasma concentrations of adiponectin and fetuin-A were determined by ELISA. Serum-derived parameters were additionally taken at 4 weeks and 6 months post-operatively. In addition, primary human hepatocytes were treated with NEFA (non-esterified fatty acid) to investigate changes in fetuin-A. BMI (body mass index) decreased significantly from 53.0±1.1 to 36.4±1.9 kg/m2 in the NAFL group and from 53.3±1.1 to 37.6±1.2 kg/m2 in the NASH group (P<0.0001) at 6 months post-surgery. This was associated with diminishing M30 and M65 (total cytokeratin-18) levels over 6 months after surgery. Adiponectin levels increased continuously in NASH patients, whereas NAFL patients plateaued at 4 weeks post-operatively. Hepatic fetuin-A mRNA and protein expression was elevated before surgery-induced weight loss. However, plasma concentrations of fetuin-A increased signficantly in NASH patients 4 weeks post-operatively. Treatment of hepatocytes with NEFA led to up-regulation of fetuin-A expression. BAS probably has a beneficial effect on NAFLD, as indicated by reduced hepatocyte apoptosis and improved adipokine profiles. In addition, fetuin-A expression is more prominent in NASH.

Serum fetuin-A levels are associated with serum triglycerides before and 6 months after bariatric surgery

“…This finding is consistent with the results of the study of Kahraman et al 18 Two other studies evaluated the changes in circulating fetuin-A at least 12 months after bariatric surgery.…”

“…Two studies that evaluated the changes in circulating fetuin-A after bariatric surgery found a decrease in serum fetuin-A levels, with one of the studies showing no change in circulating fetuin-A, though the exact metabolic role of fetuin-A in this context remains to be investigated. 14,15,18 The relationship of the changes in circulating fetuin-A with the changes in body composition after bariatric surgery has not been previously investigated. Although body weight (BW) decreases progressively during the 12 months' period following bariatric surgery, loss of lean body mass (lBM) and reduction of basal metabolic rate (BMR) occur only up until completion of the first 6 months without any further decrease in the later period.…”

A heterogeneous response of liver and skeletal muscle fat to the combination of a Paleolithic diet and exercise in obese individuals with type 2 diabetes: a randomised controlled trial

“…Circulating fetuin-A levels have been associated with severity of liver steatosis, independently of insulin resistance, and with non-alcoholic steatohepatitis [45,46]. Our results showed a strong association between fetuin-A levels and changes in liver fat content.…”

The Effect of Intraoperative N-Acetylcysteine on Hepatocellular Injury During Laparoscopic Bariatric Surgery. A Randomised Controlled Trial

“…There is only one longitudinal study showing that CK-18 fragment levels fall 6 months after surgery in patients with NASH [36]. Our data is the first of its kind measuring CK-18 fragments in the first 4 days after bariatric surgery.…”