Editorial : Cholecystectomy and NAFLD: Does Gallbladder Removal Have Metabolic Consequences?

Abstract

Pathogenesis of nonalcoholic fatty liver (NAFLD) disease and gallbladder (GB) disease secondary to cholesterol gallstones is complex, yet both conditions share similar associated risk factors, most of them related to the metabolic syndrome. Cholecystectomy, the best treatment for GB disease, is one of the most performed abdominal surgeries worldwide. In this issue of the American Journal of Gastroenterology , Ruhl and Everhart, using data from the Third United States National Health and Nutrition Examination Survey (1988 -1994), show that NAFLD is associated with cholecystectomy (odds ratio (OR) = 2.4; 1.8 -3.3), but not with gallstones (OR = 1.1; 0.84 -1.4). This fi nding suggests that cholecystectomy may itself represent a risk factor for NAFLD, which is in line with the recently undisclosed role of the GB and bile acids in systemic metabolic regulation. Thus, cholecystectomy may not be innocuous and may have a major impact on public health by contributing to NAFLD development.

Metabolic Effects of Cholecystectomy: Gallbladder Ablation Increases Basal Metabolic Rate through G-Protein Coupled Bile Acid Receptor Gpbar1-Dependent Mechanisms in Mice

“…However, a growing body of evidence contradicts this common wisdom, in fact showing that GB removal associates with increased risk for various metabolic disarrangements, including insulin resistance and fatty liver [1–3]. Concordantly, we previously found that XGB associates with elevated levels of triglycerides in the liver of mice [7], suggesting previously unrecognized roles for GB in metabolic regulation.…”

“…XGB does not change BAs pool size or synthesis rates, but significantly speeds up BAs secretion and recirculation rates [1–3]. We propose that the increased metabolic energy expended to maintain accelerated BAs kinetic, may contribute to elevated BMR after XGB.…”

Increased Risk for Obesity and Diabetes with Neurodegeneration in Developing Countries

“…Xenobiotics and its connections with various chronic diseases may involve abnormal xenobiotic biotransformation and their reactions such as oxidation, conjugation and reduction are important to its rapid metabolism and excretion in bile and urine. Chronic diseases such as gall bladder disease and hypothyroidism has increased with the metabolic syndrome and gall bladder removal now closely related to NAFLD [157,158]. The slow metabolism of xenobiotics in individuals with insulin resistance [159] may lead to dysfunction of the thyroid and hypothyroidism is now involved with the progression to obesity and diabetes [160][161][162].…”

Nutrition Therapy Regulates Caffeine Metabolism with Relevance to NAFLD and Induction of Type 3 Diabetes

“…The membrane interactions of caffeine may be completely abnormal with relevance to LPS induced membrane alterations. LPS and caffeine may interfere with hepatic cholesterol levels (Figure 4) with relevance to bile acid metabolism [151][152][153][154][155] and induction of NAFLD [156][157][158] in the developing world. Repression of Sirt 1 in cells is responsible for major intracellular defects and caffeine induced mitochondrial apoptosis relevant to adipogenesis defects [31,32] related to NAFLD with NAFLD to reach 30% of the developing world [159][160][161][162].…”

“…Defective hepatic caffeine clearance rates in the developing world may be connected to pancreatic [163][164][165][166][167][168][169][170] and thyroid disease [171][172][173] but xenobiotics may also be the inducing factor in these chronic diseases. LPS induced Sirt 1 repression may involve both caffeine and xenobiotic toxic effects with the induction of NAFLD, NAFLD linked to gall bladder disease [174][175][176][177] and cardiovascular disease [107][108][109].…”