Dataset Information

IDH2 Deficiency Aggravates Fructose-Induced NAFLD by Modulating Hepatic Fatty Acid Metabolism and Activating Inflammatory Signaling in Female Mice.

ABSTRACT: Fructose is a strong risk factor for non-alcoholic fatty liver disease (NAFLD), resulting from the disruption of redox systems by excessive reactive oxygen species production in the liver cells. Of note, recent epidemiological studies indicated that women are more prone to developing metabolic syndrome in response to fructose-sweetened beverages. Hence, we examined whether disruption of the redox system through a deletion of NADPH supplying mitochondrial enzyme, NADP?-dependent isocitrate dehydrogenase (IDH2), exacerbates fructose-induced NAFLD conditions in C57BL/6 female mice. Wild-type (WT) and IDH2 knockout (KO) mice were treated with either water or 34% fructose water over six weeks. NAFLD phenotypes and key proteins and mRNAs involved in the inflammatory pathway (e.g., NF-?B p65 and IL-1?) were assessed. Hepatic lipid accumulation was significantly increased in IDH2 KO mice fed fructose compared to the WT counterpart. Neutrophil infiltration was observed only in IDH2 KO mice fed fructose. Furthermore, phosphorylation of NF-?B p65 and expression of IL-1? was remarkably upregulated in IDH2 KO mice fed fructose, and expression of I?B? was decreased by fructose treatment in both WT and IDH2 KO groups. For the first time, we report our novel findings that IDH2 KO female mice may be more susceptible to fructose-induced NAFLD and the associated inflammatory response, suggesting a mechanistic role of IDH2 in metabolic diseases.

SUBMITTER: Pan JH

PROVIDER: S-EPMC6024877 | biostudies-other | 2018 May

REPOSITORIES: biostudies-other

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IDH2 Deficiency Aggravates Fructose-Induced NAFLD by Modulating Hepatic Fatty Acid Metabolism and Activating Inflammatory Signaling in Female Mice.

Pan Jeong Hoon JH Kim Hoe-Sung HS Beane Kaleigh Elizabeth KE Montalbano Allison Michelle AM Lee Jin Hyup JH Kim Young Jun YJ Kim Jun Ho JH Kong Byungwhi Caleb BC Kim Sangyub S Park Jeen-Woo JW Shin Eui-Cheol EC Kim Jae Kyeom JK

Nutrients 20180527 6

Fructose is a strong risk factor for non-alcoholic fatty liver disease (NAFLD), resulting from the disruption of redox systems by excessive reactive oxygen species production in the liver cells. Of note, recent epidemiological studies indicated that women are more prone to developing metabolic syndrome in response to fructose-sweetened beverages. Hence, we examined whether disruption of the redox system through a deletion of NADPH supplying mitochondrial enzyme, NADP⁺-dependent isocitrate dehydr ...[more]

PMID: 29861476

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Dataset Information

IDH2 Deficiency Aggravates Fructose-Induced NAFLD by Modulating Hepatic Fatty Acid Metabolism and Activating Inflammatory Signaling in Female Mice.

Publications

IDH2 Deficiency Aggravates Fructose-Induced NAFLD by Modulating Hepatic Fatty Acid Metabolism and Activating Inflammatory Signaling in Female Mice.

Similar Datasets

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