Abstract
BackgroundNonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Experimental studies have shown that cholecystectomy (XGB) increases hepatic fat content in mice and appears associated to NAFLD in large retrospective population-based studies. The aim of this study was to prospectively assess the effects of XGB on hepatic fat content (HFC) and insulin resistance (IR) in non-obese, middle aged Hispanic subjects.MethodsTwenty-six gallstone patients undergoing elective XGB and 16 control subjects with normal livers and gallbladders at ultrasonography were prospectively followed 24 months for changes in HFC and IR. Clinical, biochemical determinations and hepatic imaging were performed at baseline and 24 months after surgery. MRI technique quantified HFC in four hepatic segments. IR was assessed by the Homeostasis Model Assessment (HOMA-IR) index.ResultsInitial body mass index (BMI) was 25.6 ± 0.4 and 24.3 ± 1.0 in the control and XGB groups of subjects, respectively. Serum insulin level increased from 8.1 ± 0.7 to 10.0 ± 1.9 (μU/ml) 24 months after surgery in XGB patients (p < 0.05); no significant changes were detected in control individuals. Median HOMA-IR index increased from 1.31 (interquartile range, 1.01-1.68) to 2.20 (interquartile range, 1.57 - 2.60) 24 months after XGB, (p < 0.003). Median HOMA-IR index of control subjects remained unchanged at the end of the study. Serum apoB concentration increased from 61.5 ± 3.4 to 79.0 ± 7.8 (μg/ml) in XGB patients (p < 0.03). Serum apoB levels remained within normal ranges in both periods of the study in control subjects. HFC significantly increased in 2 of the 4 segments 24 months after XGB: right posterior hepatic lobe (from 5.3 ± 0.2% to 6.0 ± 0.2%, p > 0.04) and right anterior hepatic lobe (from 5.8 ± 0.2% to 6.6 ± 0.3%, p < 0.02). The average HFC of the four hepatic segments studied slightly increased from 5.4 ± 0.2 to 5.8 ± 0.3 2 years after XGB (p < 0.03). No significant changes were found in HFC in the control subjects at the end of the study.ConclusionsElective XGB increases HFC, HOMA-IR index and serum apoB concentration. These results support the notion that XGB is a risk factor non-alcoholic fatty liver disease and other IR – associated disease conditions.
Highlights
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide
It is known that insulin resistance (IR) is a fundamental pathogenic factor that alter each of the processes that regulate TG concentration in the liver by increasing hepatic lipogenesis and lipolysis from adipocytes, and decreasing peripheral lipoprotein lipase activity, producing an increase of chylomicron and Very low-density lipoprotein (VLDL) remnants, which are rapidly cleared by the liver, resulting in a net TG accumulation in the organ [16–18]
Through its critical role in regulating bile acid (BA) metabolism and the recent finding that GB mucosa is rich in the hormone Fibroblast Growth Factor 19 (FGF19), this organ may have a physiological role in whole body metabolic homeostasis [22, 23]
Summary
Nonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide. Experimental studies have shown that cholecystectomy (XGB) increases hepatic fat content in mice and appears associated to NAFLD in large retrospective population-based studies. Nonalcoholic fatty liver disease (NAFLD) is highly prevalent worldwide with an estimated rate of 30% among the adult population diagnosed by abdominal ultrasound [1–3]. Experimental studies in mice have shown that XGB increases basal metabolic rate, serum and hepatic triglycerides concentration and very low-density lipoprotein (VLDL) production [28, 29]. Since BAs are important signaling molecules in controlling lipid and carbohydrate metabolism [33–35] it is plausible that XGB may influence whole-body metabolic regulation through changes in BA physiology and potentially contributing to the development of IR and MS - associated conditions, NAFLD [19–21]
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