Exercising the hepatobiliary‐gut axis. The impact of physical activity performance

Molina-Molina, Emilio; Baccetto, Raquel; Wang, David Q.–H.; Bari, Ornella de; Krawczyk, Marcin; Portincasa, Piero

doi:10.1111/eci.12958

Cited by 51 publications

(54 citation statements)

References 187 publications

(372 reference statements)

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“…These changes can still occur in obese subjects with liver steatosis and remain under-diagnosed but still contributing to selective changes of the intestinal permeability. Sedentary behaviors and their impact on gut microbiota may play a role in this respect [88,89].…”

Section: Discussionmentioning

confidence: 99%

Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis

et al. 2020

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Intestinal permeability (IP) is essential in maintaining gut-metabolic functions in health. An unequivocal evaluation of IP, as marker of intestinal barrier integrity, however, is missing in health and in several diseases. We aimed to assess IP in the whole gastrointestinal tract according to body mass index (BMI) and liver steatosis. In 120 patients (61F:59M; mean age 45 ± SEM 1.2 years, range: 18–75), IP was distinctively studied by urine recovery of orally administered sucrose (SO, stomach), lactulose/mannitol ratio (LA/MA, small intestine), and sucralose (SA, colon). By triple quadrupole mass-spectrometry and high-performance liquid chromatography, we measured urinary recovery of saccharide probes. Subjects were stratified according to BMI as normal weight, overweight, and obesity, and answered questionnaires regarding dietary habits and adherence to the Mediterranean Diet. Liver steatosis was assessed by ultrasonography. IP at every gastrointestinal tract was similar in both sexes and decreased with age. Stomach and small intestinal permeability did not differ according to BMI. Colonic permeability increased with BMI, waist, neck, and hip circumferences and was significantly higher in obese than in lean subjects. As determined by logistic regression, the odds ratio (OR) of BMI increment was significantly higher in subjects in the highest tertile of sucralose excretion, also after adjusting for age and consumption of junk food. The presence of liver steatosis was associated with increased colonic permeability. Patients with lower score of adherence to Mediterranean diet had a higher score of ‘junk food’. Intestinal permeability tended to increase in subjects with a lower adherence to Mediterranean diet. In conclusion, colonic (but not stomach and small intestinal) permeability seems to be linked to obesity and liver steatosis independently from dietary habits, age, and physical activity. The exact role of these last factors, however, requires specific studies focusing on intestinal permeability. Results should pave the way to both primary prevention measures and new therapeutic strategies in metabolic and liver diseases.

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Section: Discussionmentioning

confidence: 99%

Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis

et al. 2020

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“…Finally, physical exercise and progressive weight loss, the two most potent interventions to restore systemic and hepatic insulin sensitivity in patients with common forms of IR, have also shown beneficial for GSD, both in primary and secondary prevention studies . The mechanisms for this exercise‐associated ameliorated lithogenesis are possibly related to improved lipid profile in the bile and to improved GB emptying/refilling processes . Mechanistically, endurance training promotes cholesterol uptake by the liver but also its conversion to BAs, leading to reduced gallstone formation upon a lithogenic diet in mice …”

Section: Hepatic Ir As a Potential Determinant Of Gsdmentioning

confidence: 99%

“…107 The mechanisms for this exercise-associated ameliorated lithogenesis are possibly related to improved lipid profile in the bile and to improved GB emptying/refilling processes. 107 Mechanistically, endurance training promotes cholesterol uptake by the liver but also its conversion to BAs, leading to reduced gallstone formation upon a lithogenic diet in mice. 108…”

Section: Hepatic Ir As a Potential Determinant Of Gsdmentioning

confidence: 99%

Pathophysiological connections between gallstone disease, insulin resistance, and obesity

2019

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Summary Obesity and cholesterol gallstone disease (GSD) are frequently coexisting diseases; therefore and considering the current worldwide obesity epidemics, a precise understanding of the pathophysiological relationships between GSD and insulin resistance (IR) is important. Classically, obesity has been understood as a risk factor for GSD and the gallbladder (GB) viewed as a simple bile reservoir, with no metabolic roles whatsoever. However, consistent evidence has showed that both GSD and cholecystectomy associates with fatty liver and IR, raising the possibility that the GB is indeed an organ with metabolic regulatory roles. Herein, we review the pathophysiological mechanisms by which GSD, IR, and obesity are interconnected, with emphasis in the actions of the GB as a regulator of bile acids kinetics and a hormone secreting organ, with metabolic actions at the systemic level. We also examine the relationships between increased hepatic lipogenic in IR states and GSD pathogenesis. We propose a model in which GSD and hepatic IR mutually interact to determine a state of dysregulated lipid and energy metabolism that potentiate the metabolic dysregulation of obesity.

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“…chronic exercise, defined as a training program of repeated exercises of either an endurance or resistance type, lasting at least 8 weeks), is the primary recommended therapy for NAFLD . Several studies have documented the benefit of physical activity on the reduction of liver fat . However, elderly people could have difficulty in undertaking physical activities, with a risk of muscle damage and bone fracture.…”

Section: Introductionmentioning

confidence: 99%

“…7 Several studies have documented the benefit of physical activity on the reduction of liver fat. [8][9][10] However, elderly people could have difficulty in undertaking physical activities, with a risk of muscle damage and bone fracture. For this reason, the effect of knee loading, a joint loading technique that applies dynamic lateral loads to the knee as a supportive substitute for physical activities, has been evaluated as an alternative to exercise.…”

Section: Introductionmentioning

confidence: 99%

Hepatic gene expression in mouse models of non‐alcoholic fatty liver disease after acute exercise

Piguet

Guarino

Potaczek

et al. 2019

Hepatology Research

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Aim Non‐alcoholic fatty liver disease (NAFLD) patients benefit from physical exercise. This study aimed to investigate the effect of acute exercise on hepatic gene expression in different mouse models of NAFLD. Methods C57BL/6J mice were fed with a control (CD) or a high fat (HFD) diet. AlbCrePtenflox/flox (Pten‐KO) and Fxr−/− mice, two genetic models of NAFLD with insulin hypersensitivity and resistance, respectively, were fed with CD. After 4 weeks, mice were randomly assigned to exercise or sedentariness. Mice were killed 15 min or 3 h after the running/sedentary period. Genome‐wide hepatic gene expression was evaluated with the Illumina Micro‐array platform. Quantitative polymerase chain reaction confirmed changes in gene expression. Results Acute exercise transiently affected the expression of genes involved in the immune response in C57BL/6 mice fed with CD and this effect normalized in the recovery phase. Acute exercise affected genes involved in gluconeogenesis in the insulin resistant Fxr−/− model. Genes involved in lipid metabolism were affected in C57BL/6 mice fed with CD, but not in mouse models of NAFLD. Genes involved in DNA damage response pathways were deregulated only in C57BL/6 mice fed with CD and not in mouse models of NAFLD. Conclusion The simultaneous analysis of different NAFLD models revealed that an acute exercise bout affects hepatic gene expression differentially according to animal models and that most of the differentially expressed genes are involved in glucose and fatty acid metabolism, immune regulation, and DNA damage response.

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Exercising the hepatobiliary‐gut axis. The impact of physical activity performance

Abstract: Several beneficial effects of physical activity are anticipated on metabolic disorders linking liver steatosis, gallstone disease, gut motility, enterohepatic circulation of signalling bile acids in relation to intestinal microbiota and inflammatory changes.

Cited by 51 publications

References 187 publications

Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis

Increased Colonic Permeability and Lifestyles as Contributing Factors to Obesity and Liver Steatosis

Pathophysiological connections between gallstone disease, insulin resistance, and obesity

Hepatic gene expression in mouse models of non‐alcoholic fatty liver disease after acute exercise

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