Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity

Hartmann, Phillipp; Seebauer, Caroline T.; Mazagova, Magdalena; Horvath, Angela; Wang, Lirui; Llorente, Cristina; Varki, Nissi; Brandl, Katharina; Ho, Samuel B.; Schnabl, Bernd

doi:10.1152/ajpgi.00094.2015

Cited by 41 publications

(43 citation statements)

References 48 publications

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“…Gut microbiota is recognized as a major contributor to HFD induced obesity and metabolic disorder [8–10, 42]. Antibiotics markedly reduce obesity development in mice and improved gut pathophysiological status is believed to be the main underlying mechanism.…”

Section: Discussionmentioning

confidence: 99%

Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice

Luo

Jiang

et al. 2017

Oncotarget

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The prevalence of non-alcoholic fatty liver disease is increasing rapidly worldwide. However, effective strategies for combating high-fat diet (HFD) induced obesity, fatty liver and metabolic disorder are still limited, and outcomes remain poor. In the present study, we evaluated the combined actions of dietary capsaicin and antibiotics on HFD-induced physiological abnormalities in mice. C57BL/6 male mice were fed with HFD (60% calories from fat) for 17 weeks, and the resultant pathophysiological effects were examined. Antibiotic treatment markedly attenuated gut inflammation and leakiness induced by HFD, whereas capsaicin showed limited effects on the gut. However, dietary capsaicin significantly increased PPAR-α expression in adipose tissue, while antibiotics had no such effect. Animals treated with a combination of capsaicin and antibiotics had the smallest body weight gain and fat pad index, as well as the lowest hepatic fat accumulation. Combination treatment also maximally improved insulin responsiveness, as indicated by insulin tolerance tests. These results suggest the co-treatment of capsaicin and antibiotics, a novel combination strategy, would play synergistically to attenuate the HFD-induced obesity, fatty liver and metabolic disorder.

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Section: Discussionmentioning

confidence: 99%

Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice

Luo

Jiang

et al. 2017

Oncotarget

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“…44 Modulation of the gut immune system in beta 7 integrin-deficient mice through use of 5-aminosylicylclic acid as a topical anti-inflammatory improved metabolic parameters and reduced gut permeability and endotoxemia. 45 Downstream effects of endotoxin translocation may include induction of toll-like receptors (TLR) in the liver, specifically TLR4, with downstream activation of transcription factors inducing an inflammatory response, and TLR4 knockout may mitigate hepatic inflammation.…”

Section: Postulated Mechanisms Linking the Gut Microbiome To Nafldmentioning

confidence: 99%

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

Sharpton

Ajmera

Loomba

2019

Clinical Gastroenterology and Hepatology

135

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The gut microbiome, a diverse microbial community in the gastrointestinal tract, plays a pivotal role in the maintenance of health. The gut microbiome metabolizes dietary and host-derived molecules to produce bioactive metabolites, which have a wide array of effects on host metabolism and immunity. 'Dysbiosis' of the gut microbiome, commonly considered as perturbation of microbiome diversity and composition, has been associated with intestinal and extra-intestinal diseases, including nonalcoholic fatty liver disease (NAFLD). A number of endogenous and exogenous factors, such as nutritional intake and xenobiotic exposure, can alter the gut microbiome. We will review the evolving methods for studying the gut microbiome and how these profiling techniques have been utilized to further our understanding of the gut microbial community composition and functional potential in the clinical spectrum of NAFLD. We will highlight microbiome-host interactions that may contribute to the pathogenesis of NAFLD, with a primary focus on mechanisms related to the metabolic output of the gut microbiome. Finally, we will discuss potential therapeutic implications of the gut microbiome in NAFLD.

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“…Intestinal dysbiosis contributes to the development of NAFLD and NASH . Transmission of the hepatic phenotype by microbiota transplantation to germ‐free mice or cohousing of mice underlines the role of intestinal dysbiosis for liver disease .…”

Section: Introductionmentioning

confidence: 99%

“…Intestine‐specific overexpression of REG3G reduced mucosa adherent bacteria, decreased bacterial translocation, and protected mice from liver disease following chronic ethanol administration . In animal models of diet‐induced obesity, intestinal Il‐22 and Reg3g are down‐regulated . Here, we investigated the role of REG3B and REG3G on bacterial translocation and liver disease in a mouse model of diet‐induced NASH.…”

Section: Introductionmentioning

confidence: 99%

“…Intestinal dysbiosis contributes to the development of NAFLD and NASH. (2)(3)(4) Transmission of the hepatic Abbreviations: AST, aspartate aminotransferase; Ctrl, control chow; FFD, Western style fast food diet; GTT, glucose tolerance test; IL, interleukin; ITT, insulin tolerance test; LPS, lipopolysaccharide; MLN, mesenteric lymph nodes; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis; Reg3b, regenerating islet-derived protein 3 beta; Reg3g, regenerating islet-derived protein 3 gamma; Tg, transgenic; TGFb, transforming growth factor b; TLR-4, toll-like receptor 4; TNF-a, tumor necrosis factor a; WT, wild type. phenotype by microbiota transplantation to germ-free mice or cohousing of mice underlines the role of intestinal dysbiosis for liver disease.…”

Section: Introductionmentioning

confidence: 99%

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The Role of Intestinal C‐type Regenerating Islet Derived‐3 Lectins for Nonalcoholic Steatohepatitis

Bluemel

Martino²,

Lee

et al. 2018

Hepatology Communications

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C‐type regenerating islet derived‐3 (Reg3) lectins defend against pathogens and keep commensal bacteria at a distance. Deficiency of Reg3g and Reg3b facilitates alcohol‐induced bacterial translocation and alcoholic liver disease. Intestinal Reg3g is down‐regulated in animal models of diet‐induced obesity, but the functional consequences for nonalcoholic steatohepatitis (NASH) are unknown. The aim of this study was to investigate the role of Reg3 lectins in NASH. NASH was induced by a Western‐style fast‐food diet in mice deficient for Reg3g or Reg3b and in transgenic mice overexpressing Reg3g in intestinal epithelial cells (Reg3gTg). Glucose tolerance was assessed after 18 weeks and insulin resistance after 19 weeks of feeding. After 20 weeks, mice were assessed for features of the metabolic syndrome. Obesity was not different in genetically modified mice compared with their respective wild‐type littermates. Glucose intolerance, liver injury, hepatic inflammation, steatosis, fibrosis, and bacterial translocation to mesenteric lymph nodes and to the liver were not different in Reg3g‐deficient mice compared with wild‐type littermates. Plasma endotoxin levels were higher in Reg3g‐deficient mice. Reg3b deficiency protected against glucose intolerance, but liver disease, bacterial translocation, and plasma endotoxin levels were similar to wild‐type littermates. Absence of either REG3G or REG3B protein in the ileum was not compensated for by up‐regulation of the respective other REG3 protein. Transgenic Reg3g mice also developed liver injury, steatosis, and fibrosis similar to their wild‐type littermates. Conclusion: In contrast to alcoholic liver disease, loss of intestinal Reg3 lectins is not sufficient to aggravate diet‐induced obesity and NASH. This supports a multi‐hit pathogenesis in NASH. Only glucose metabolism is affected by Reg3b deficiency. (Hepatology Communications 2018;2:393‐406)

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Deficiency of intestinal mucin-2 protects mice from diet-induced fatty liver disease and obesity

Cited by 41 publications

References 48 publications

Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice

Dietary capsaicin and antibiotics act synergistically to reduce non-alcoholic fatty liver disease induced by high fat diet in mice

Emerging Role of the Gut Microbiome in Nonalcoholic Fatty Liver Disease: From Composition to Function

The Role of Intestinal C‐type Regenerating Islet Derived‐3 Lectins for Nonalcoholic Steatohepatitis

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