Browsing by Subject "hepatic steatosis"

Now showing 1 - 4 of 4
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    ChREBP, SIRT1 and ethanol metabolism– a complicated network in alcohol-induced hepatic steatosis.
    (Wiley, 2015-10) Liangpunsakul, Suthat; Department of Medicine, IU School of Medicine
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    High fat diet rescues disturbances to metabolic homeostasis and survival in the Id2 null mouse in a sex-specific manner
    (Elsevier B.V., 2014-08-29) Zhou, Peng; Hummel, Alyssa D.; Pywell, Cameron M.; Dong, X. Charlie; Duffield, Giles E.; Department of Biochemistry & Molecular Biology, IU School of Medicine
    Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated that Id2 null mice have altered expression of circadian genes involved in lipid metabolism, altered circadian feeding behavior, and sex-specific enhancement of insulin sensitivity and elevated glucose uptake in skeletal muscle and brown adipose tissue. Here we further characterized the Id2−/− mouse metabolic phenotype in a sex-specific context and under low and high fat diets, and examined metabolic and endocrine parameters associated with lipid and glucose metabolism. Under the low-fat diet Id2−/− mice showed decreased weight gain, reduced gonadal fat mass, and a lower survival rate. Under the high-fat diet, body weight and gonadal fat gain of Id2−/− male mice was comparable to control mice and survival rate improved markedly. Furthermore, the high-fat diet treated Id2−/− male mice lost the enhanced glucose tolerance feature observed in the other Id2−/− groups, and there was a sex-specific difference in white adipose tissue storage of Id2−/− mice. Additionally, a distinct pattern of hepatic lipid accumulation was observed in Id2−/− males: low lipids on the low-fat diet and steatosis on the high-fat diet. In summary, these data provides valuable insights into the impact of Id2 deficiency on metabolic homeostasis of mice in a sex-specific manner.
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    Inhibition of Secretin/Secretin Receptor Axis Ameliorates NAFLD Phenotypes
    (Wiley, 2021-10) Chen, Lixian; Wu, Nan; Kennedy, Lindsey; Francis, Heather; Ceci, Ludovica; Zhou, Tianhao; Samala, Niharika; Kyritsi, Konstantina; Wu, Chaodong; Sybenga, Amelia; Ekser, Burcin; Dar, Wasim; Atkins, Constance; Meadows, Vik; Glaser, Shannon; Alpini, Gianfranco; Surgery, School of Medicine
    Background & Aims Human non-alcoholic fatty liver disease (NAFLD) is characterized at early stages by hepatic steatosis, which may progress to nonalcoholic steatohepatitis (NASH) when the liver displays microvesicular steatosis, lobular inflammation, and pericellular fibrosis. The secretin (SCT)/secretin receptor (SCTR) axis promotes biliary senescence and liver fibrosis in cholestatic models through downregulation of miR-125b signaling. We aim to evaluate the effect of disrupting biliary SCT/SCTR/miR-125b signaling on hepatic steatosis, biliary senescence and liver fibrosis in NAFLD/NASH. Approach & Results In vivo, 4 wk male WT, Sct-/- and Sctr-/- mice were fed a control diet (CD) or high-fat diet (HFD) for 16 wks. The expression of SCT/SCTR/miR-125b axis was measured in human NAFLD/NASH liver samples and HFD mouse livers by immunohistochemistry (IHC) and qPCR. Biliary/hepatocyte senescence, ductular reaction and liver angiogenesis were evaluated in mouse liver and human NAFLD/NASH liver samples. miR-125b target lipogenesis genes in hepatocytes were screened and validated by custom RT2 Profiler PCR array and luciferase assay. Biliary SCT/SCTR expression was increased in human NAFLD/NASH samples and in livers of HFD mice, whereas the expression of miR-125b was decreased. Biliary/hepatocyte senescence, ductular reaction, and liver angiogenesis were observed in human NAFLD/NASH samples as well as HFD mice, which were decreased in Sct-/- and Sctr-/- HFD mice. Elovl1 is a lipogenesis gene targeted by miR-125b, and its expression was also decreased in HFD mouse hepatocytes following Sct or Sctr knockout. Bile acid profile in fecal samples have the greatest changes between WT mice and Sct-/-/Sctr-/- mice. Conclusion The biliary SCT/SCTR/miR-125b axis promotes liver steatosis by upregulating lipid biosynthesis gene Elovl1. Targeting the biliary SCT/SCTR/miR-125b axis may be key for ameliorating phenotypes of human NAFLD/NASH.
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    Nonalcoholic Fatty Liver Disease: Making the Diagnosis
    (Wiley, 2020-09-04) Tariq, Tooba; Desai, Archita P.; Medicine, School of Medicine