Hepatic Expression of ACBP Is a Prognostic Marker for Weight Loss After Bariatric Surgery

Abstract

The incidence and prevalence of obesity and related cardio-metabolic diseases are on the rise, posing a critical health care challenge to systems across the globe. Bariatric surgery is a therapeutic cornerstone for morbidly obese patients, besides novel medical treatments, partly by ameliorating metabolic inflammation, a hallmark of metabolic diseases. Acyl-CoA Binding Protein (ACBP), also known as diazepam-binding inhibitor (DBI), is a regulator of autophagy and metabolism, and has recently been shown to increase in individuals undergoing voluntary fasting and in patients with cancer cachexia-induced malnutrition. By analyzing a prospectively collected study with matched serum and liver samples from patients undergoing laparoscopic adjustable gastric banding at baseline and six months after surgery, we here demonstrate that ACBP serum levels significantly increase following bariatric surgery. Hepatic ACBP expression at baseline predicted weight loss six months after the procedure. The predictive value of ACBP warrants further study, as it could identify patients who benefit most from metabolic surgery in the future.

Keywords: ACBP; DBI; bariatric surgery; weight loss.

Figure 1

Serum levels of ACBP/DBI increase significantly 6 months after bariatric surgery. (A) ACBP/DBI levels in sera of patients at the time point of bariatric surgery and 6 months after surgery, n = 29; (B) mRNA expression levels in liver tissue samples of ACBP/DBI at the time of bariatric surgery and 6 months after surgery, n = 23 (C); mRNA levels of ACBP/DBI in adipose tissue at the time of bariatric surgery and 6 months after surgery, n = 10. Statistical significance was assessed using a Wilcoxon matched-pairs signed rank test (A,B) or a paired student’s t-test (C). **** p ≤ 0.0001; ns not significant.

Figure 2

A lower expression of ACBP/DBI in liver tissue at time point of operation is observable in patients with a better treatment response. (A) mRNA expression levels of ACBP/DBI in liver tissue samples at the time of bariatric surgery n = 15 responder, n = 7 non-responder; (B,C) Correlation of ACBP/DBI mRNA expression levels in liver tissue at time point of bariatric surgery with KFL3 (B) and METRNL (C) mRNA expression in liver tissue n = 23; (D) Serum levels of patients undergoing bariatric surgery at the time of surgery, compared between responders (weight loss ≥ 20 kg) and non-responders (weight loss < 20 kg) n = 15 responder, n = 14 non-responder. Statistical significance was assessed using a simple linear regression to assess if the slope is significantly non-zero (B,C), or an unpaired student’s t-test (A,D). **** p ≤ 0.0001; ns not significant.

Figure 3

Higher ACBP/DBI serum levels are associated with higher steatosis and fibrosis score 6 months after LAGB. (A) Histological scores for steatosis at the time of bariatric surgery (TP0) or six months after surgery (TP6) n = 14; (B) Correlation between ACBP/DBI serum levels at the time of bariatric surgery and the histological grade of steatosis six months after surgery n = 13; (C) Correlation between ACBP/DBI serum levels at the time of bariatric surgery and the histological grade of fibrosis six months after surgery n = 13. Statistical significance was assessed using a Wilcoxon matched-pairs signed rank (A) or a simple linear regression to assess if the slope is significantly non-zero (B,C). *** p ≤ 0.001.

Figure 4

Higher ACBP/DBI serum levels are associated with higher histological NAS score. (A) Correlation of NAS and serum ACBP/DBI levels at the time of bariatric surgery n = 13; (B) comparison of serum ACBP/DBI levels between NAS ≤ 4 and NAS ≥ 5; n = 6 NAS ≤ 4, n = 7 NAS ≥ 5; (C) Correlation between ACBP/DBI serum levels at the time of bariatric surgery and the NAS 6 months after surgery n = 13; (D) Correlation of NAS and ACBP/DBI mRNA levels in liver tissue at the time of bariatric surgery n = 12; (E) comparison of mRNA liver tissue expression of ACBP/DBI between NAS ≤ 4 and NAS ≥ 5; n = 5 NAS ≤ 4, n = 6 NAS ≥ 5. Statistical significance was assessed using a Mann-Whitney test (B,E) or a simple linear regression to assess if the slope is significantly non-zero (A,C,D). *** p ≤ 0.001; ns not significant.

Figure 5

LPS reduces ACBP/DBI expression in PBMC of healthy donors but not in an in vitro hepatocyte cell culture model. (A,B) ACBP/DBI expression levels in PBMC of healthy donors (B) or the human hepatocyte cell line HepG2 (B) stimulated with LPS, IL-1β, TNFα, or vehicle for 24 h, n = 3 (A) and n = 4 (B). Statistical significance was assessed with a one-way Anova with Sidak’s multiple comparison. ** p ≤ 0.01.