Gastric Bypass Increases Circulating Bile Acids and Activates Hepatic Farnesoid X Receptor (FXR) but Requires Intact Peroxisome Proliferator Activator Receptor Alpha (PPARα) Signaling to Significantly Reduce Liver Fat Content

Mazzini, Guilherme S.; Khoraki, Jad; Browning, Matthew G.; Wu, Jilin; Zhou, Huiping; Price, Elvin; Wolfe, Luke; Mangino, Martin J.; Campos, Guilherme M.

doi:10.1007/s11605-021-04908-3

Cited by 11 publications

(3 citation statements)

References 29 publications

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“…Bile acids also act as FXR agonists. Although bile acids were not measured in this study, previous studies have shown that circulating levels of bile acids are increased after RYGB [ 39 , 40 ], which may partly explain the lowering of Lp(a) levels among the surgical patients. Interestingly, bile acid synthesis and levels have been shown to be increased in women with obesity, and to be normalized within 3 days on a caloric restriction diet [ 41 ].…”

Section: Discussionmentioning

confidence: 93%

Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids

et al. 2022

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Background Limited evidence suggests that surgical and non-surgical obesity treatment differentially influence plasma Lipoprotein (a) [Lp(a)] levels. Further, a novel association between plasma arachidonic acid and Lp(a) has recently been shown, suggesting that fatty acids are a possible target to influence Lp(a). Here, the effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) were compared, and it was examined whether the effects were mediated by changes in plasma fatty acid (FA) levels. Methods The study includes two independent trials of patients with overweight or obesity. Trial 1: Two-armed intervention study including 82 patients who underwent a 7-week low energy diet (LED), followed by Roux-en-Y gastric bypass and 52-week follow-up (surgery-group), and 77 patients who underwent a 59-week energy restricted diet- and exercise-program (lifestyle-group). Trial 2: A clinical study including 134 patients who underwent a 20-week very-LED/LED (lifestyle-cohort). Results In the surgery-group, Lp(a) levels [median (interquartile range)] tended to increase in the pre-surgical LED-phase [17(7–68)-21(7–81)nmol/L, P = 0.05], but decreased by 48% after surgery [21(7–81)—11(7–56)nmol/L, P < 0.001]. In the lifestyle-group and lifestyle-cohort, Lp(a) increased by 36%[14(7–77)—19(7–94)nmol/L, P < 0.001] and 14%[50(14–160)—57(19–208)nmol/L, P < 0.001], respectively. Changes in Lp(a) were independent of weight loss. Plasma levels of total saturated FAs remained unchanged after surgery, but decreased after lifestyle interventions. Arachidonic acid and total n-3 FAs decreased after surgery, but increased after lifestyle interventions. Plasma FAs did not mediate the effects on Lp(a). Conclusion Bariatric surgery reduced, whereas lifestyle interventions increased plasma Lp(a), independent of weight loss. The interventions differentially influenced changes in plasma FAs, but these changes did not mediate changes in Lp(a). Trial registration Trial 1: Clinicaltrials.gov NCT00626964. Trial 2: Netherlands Trial Register NL2140 (NTR2264). Graphical abstract

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Section: Discussionmentioning

confidence: 93%

Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids

et al. 2022

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“…Although outside the scope of this review, animal studies can be used to further develop and evaluate hypotheses [136][137][138][139]. For example, a recent study in rats concluded that RYGB led to greater liver fat loss compared to a low-calorie diet, possibly due to increased fasting bile acid levels and the increased expression of modulators of liver fat oxidation, FXR and PPARα (peroxisome proliferator activator receptor alpha) [140]. Intervention with resveratrol altered the gut microbiota and improved hepatic steatosis and insulin resistance in mice [141].…”

Section: Discussion and Future Perspectivesmentioning

confidence: 99%

Gut Microbiome and Metabolites in Patients with NAFLD and after Bariatric Surgery: A Comprehensive Review

et al. 2021

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The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing, as are other manifestations of metabolic syndrome such as obesity and type 2 diabetes. NAFLD is currently the number one cause of chronic liver disease worldwide. The pathophysiology of NAFLD and disease progression is poorly understood. A potential contributing role for gut microbiome and metabolites in NAFLD is proposed. Currently, bariatric surgery is an effective therapy to prevent the progression of NAFLD and other manifestations of metabolic syndrome such as obesity and type 2 diabetes. This review provides an overview of gut microbiome composition and related metabolites in individuals with NAFLD and after bariatric surgery. Causality remains to be proven. Furthermore, the clinical effects of bariatric surgery on NAFLD are illustrated. Whether the gut microbiome and metabolites contribute to the metabolic improvement and improvement of NAFLD seen after bariatric surgery has not yet been proven. Future microbiome and metabolome research is necessary for elucidating the pathophysiology and underlying metabolic pathways and phenotypes and providing better methods for diagnostics, prognostics and surveillance to optimize clinical care.

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“…Bile acid signaling also contributes to the resolution of NAFLD after BS, as RYGB causes an increase in total BAs, and this is related to the normalized accumulation of liver fat. Improvements in NAFLD after RYGB are attenuated by inhibiting PPARα ( Mazzini et al, 2021 ). The complex mechanisms of BS in resolving NAFLD, including the gut microbiome and gastrointestinal hormones, require comprehensive investigation.…”

Section: Bariatric Surgery and Non-alcoholic Fatty Liver Diseasementioning

confidence: 99%

Gut microbiome and microbial metabolites in NAFLD and after bariatric surgery: Correlation and causality

Ren

Yang

et al. 2022

Front. Microbiol.

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Non-alcoholic fatty liver disease (NAFLD) is currently related to a heavy socioeconomic burden and increased incidence. Since obesity is the most prevalent risk factor for NAFLD, weight loss is an effective therapeutic solution. Bariatric surgery (BS), which can achieve long-term weight loss, improves the overall health of patients with NAFLD. The two most common surgeries are the Roux-en-Y gastric bypass and sleeve gastrectomy. The gut-liver axis is the complex network of cross-talking between the gut, its microbiome, and the liver. The gut microbiome, involved in the homeostasis of the gut-liver axis, is believed to play a significant role in the pathogenesis of NAFLD and the metabolic improvement after BS. Alterations in the gut microbiome in NAFLD have been confirmed compared to that in healthy individuals. The mechanisms linking the gut microbiome to NAFLD have been proposed, including increased intestinal permeability, higher energy intake, and other pathophysiological alterations. Interestingly, several correlation studies suggested that the gut microbial signatures after BS become more similar to those of lean, healthy controls than that of patients with NAFLD. The resolution of NAFLD after BS is related to changes in the gut microbiome and its metabolites. However, confirming a causal link remains challenging. This review summarizes characteristics of the gut microbiome in patients with NAFLD before and after BS and accumulates existing evidence about the underlying mechanisms of the gut microbiome.

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Gastric Bypass Increases Circulating Bile Acids and Activates Hepatic Farnesoid X Receptor (FXR) but Requires Intact Peroxisome Proliferator Activator Receptor Alpha (PPARα) Signaling to Significantly Reduce Liver Fat Content

Cited by 11 publications

References 29 publications

Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids

Differential effects of bariatric surgery and lifestyle interventions on plasma levels of Lp(a) and fatty acids

Gut Microbiome and Metabolites in Patients with NAFLD and after Bariatric Surgery: A Comprehensive Review

Gut microbiome and microbial metabolites in NAFLD and after bariatric surgery: Correlation and causality

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