Fibroblast Growth Factor 19 Treatment Ameliorates Disruption of Hepatic Lipid Metabolism in Farnesoid X Receptor (Fxr)-Null Mice

Miyata, Masaaki; Sakaida, Yumi; Matsuzawa, Hitomi; Yoshinari, Kouichi; Yamazoe, Yasushi

doi:10.1248/bpb.34.1885

Cited by 69 publications

(39 citation statements)

References 35 publications

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“…Interestingly, a few studies showed that FGF19 transgenic mice were resistant to diet-induced obesity and insulin resistance (Tomlinson et al, 2002;Fu et al, 2004). In addition, FGF19 has been shown to repress hepatic glucose production (Potthoff et al, 2011), promote glycogen synthesis (Kir et al, 2011), repress lipogenesis (Bhatnagar et al, 2009;Miyata et al, 2011a), and increase metabolic rate (Tomlinson et al, 2002;Fu et al, 2004). Fgf15 knockout mice showed glucose intolerance, increased hepatic gluconeogenesis, and reduced hepatic glycogen storage but unaltered overall insulin sensitivity.…”

Section: Bile Acid Receptor Signaling In Liver Metabolismmentioning

confidence: 99%

Bile Acid Signaling in Metabolic Disease and Drug Therapy

2014

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Section: Bile Acid Receptor Signaling In Liver Metabolismmentioning

confidence: 99%

Bile Acid Signaling in Metabolic Disease and Drug Therapy

2014

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“…The cholesterol accumulation was thought to be due to an increase in intestinal BA reabsorption. Follow-up studies supported Weismann's hypothesis by showing that GF animals have elevated levels of conjugated BA throughout the intestine with no deconjugation and strongly decreased fecal excretion [ 115 ]; and later it was also confi rmed in studies with mice treated with antibiotics [ 116 ]. Those previous studies showed that the gut microbiota reduces the bile acid pool size with its greatest effect on βMCA rather than CA levels.…”

Section: Microbiota and Bile Acid Metabolismmentioning

confidence: 70%

Role of Microbiota in Regulating Host Lipid Metabolism and Disease Risk

Bondia‐Pons

Hyötyläinen

Orešič

2014

Molecular and Integrative Toxicology

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The gut microbiota is an environmental factor which affects host metabolism and correspondingly contributes to obesity and its cardiometabolic comorbidities. However, the mechanisms behind the regulation of host lipid metabolism by gut microbiota are poorly understood. The mechanistic in vivo studies over the past decade combining gnotobiotic animal models, metagenomics, and metabolomics have begun to decipher the role of the gut microbiota in the regulation of host physiology. However, since the animal studies cannot be easily extrapolated to humans, it still remains unclear if an altered microbiota associated with a specifi c disease in humans is a causative factor or merely a consequence of the disease state or both. Cheaper and more comprehensive sequencing tools for the analysis of gut microbiota, together with the recent advances in mass spectrometry-based analysis of molecular lipids, are expected to contribute to our understanding of the mechanisms linking gut microbiota, host lipid metabolism, and how they together contribute to metabolic comorbidities of obesity. Keywords The Link Between Lipids and Gut MicrobiotaAdvances in the study of microbiomes by culture-independent molecular methods based on the ribosomal 16S sequence have revolutionized the analysis of gut microbiota. Metagenomic sequencing has confi rmed that the human gut microbiota is a very complex community of about 100 trillion archaeal and bacterial cells corresponding to over more than 1,000 species [ 1 ]. The community is dominated by bacteria belonging I. Bondia-Pons • T. Hyötyläinen • M. Orešič (*)

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“…Enhanced PPARα signaling is likely to be involved in the reduction of hepatic and serum triglyceride levels in Fxr-null mice of the fish oil group. In our previous study, human FGF19-treated Fxr-null mice showed decreased hepatic lipid levels and serum ALT activity (Miyata et al, 2011). FGF15/19 is an intestinal endocrine hormone that regulates hepatic lipid metabolism through hepatic FGF receptor 1 and 4 (Jones, 2008;Kir et al, 2011).…”

Section: Discussionmentioning

confidence: 93%

“…The hepatic S9 and mitochondrial fractions were prepared as described previously (Miyata et al, 2011). Goat anti-Scd1 antibody (S-15: Santa Cruz Biotechnology, Dallas, TX, USA), rabbit anti-Fas antibody (H300: Santa Cruz Biotechnology), rabbit anti-Cpt2 antibody (EPR13626: Abcam, Cambridge, UK), rabbit anti-Cpt1A antibody (15184-1-AP: Proteintech Group Inc., Chicago, IL, USA), rabbit anti-Cox IV antibody (11242-1-AP: Proteintech Group Inc.) and monoclonal anti-β-actin antibody (AC-15: Sigma-Aldrich, St. Louis, MO, USA) were used as primary antibodies.…”

Section: Western Blot Analysismentioning

confidence: 99%

Fish oil feeding reverses hepatomegaly and disrupted hepatic function due to the lack of FXR signaling

et al. 2017

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-Mice lacking farnesoid X receptor (FXR) are used as a model for nonalcoholic fatty liver disease because their livers exhibit hepatomegaly, hepatic steatosis, and hepatic inflammation. The influence of fish oil feeding on hepatomegaly and disrupted hepatic function was investigated using female Fxr-null mice and wild-type mice fed a fish oil diet (2% fish oil and 2% corn oil) or a control diet (4% corn oil) for 4 weeks. Hepatic n-3 polyunsaturated fatty acid (PUFA) levels, including 22:6 n-3 docosahexaenoic acid (DHA) and 20:5 n-3 eicosapentaenoic acid (EPA) were significantly higher in the fish oil group than those in the control group of Fxr-null mice and wild-type mice. Fxr-null mouse livers of the control group showed a whitish brown coloration, whereas Fxr-null mouse livers of the fish oil group showed a dark brown coloration similar to that of wild-type mice. The liver in Fxr-null mice of the fish oil group was smaller than that of the control group. There was a significant decrease in the levels of hepatic damage-associated diagnostic markers, hepatic and serum bile acids, triglycerides, free fatty acids, and total cholesterol levels in Fxr-null mice because of fish oil feeding. It also reversed elevated mRNA levels of oxidative stress-related genes (Hmox1, Gsta1, and Gsta2) and reduced mRNA levels of transcriptional factors (Pparα and Shp) in Fxr-null mice. These results suggest that fish oil feeding reverses hepatomegaly and disrupted hepatic function due to the lack of FXR signaling.

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Fibroblast Growth Factor 19 Treatment Ameliorates Disruption of Hepatic Lipid Metabolism in Farnesoid X Receptor (Fxr)-Null Mice

Cited by 69 publications

References 35 publications

Bile Acid Signaling in Metabolic Disease and Drug Therapy

Bile Acid Signaling in Metabolic Disease and Drug Therapy

Role of Microbiota in Regulating Host Lipid Metabolism and Disease Risk

Fish oil feeding reverses hepatomegaly and disrupted hepatic function due to the lack of FXR signaling

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