Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition

Sonal S. Sheth; Lawrence W. Castellani; Soumya Chari; Cory Wagg; Christopher K. Thipphavong; Jackie S. Bodnar; Peter Tontonoz; Alan D. Attie; Gary D. Lopaschuk; Aldons J. Lusis

Journal of Lipid Research (Jan 2005)

Thioredoxin-interacting protein deficiency disrupts the fasting-feeding metabolic transition

Sonal S. Sheth,
Lawrence W. Castellani,
Soumya Chari,
Cory Wagg,
Christopher K. Thipphavong,
Jackie S. Bodnar,
Peter Tontonoz,
Alan D. Attie,
Gary D. Lopaschuk,
Aldons J. Lusis

Affiliations

Sonal S. Sheth: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Lawrence W. Castellani: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Soumya Chari: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Cory Wagg: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Christopher K. Thipphavong: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Jackie S. Bodnar: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Peter Tontonoz: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Alan D. Attie: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Gary D. Lopaschuk: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706
Aldons J. Lusis: Departments of Human Genetics, Medicine, Molecular Biology Institute, and Microbiology, Immunology, & Molecular Genetics, University of California, Los Angeles, David Geffen School of Medicine at UCLA, Los Angeles, CA 90095; Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G 2S2; Molecular Biology Institute, Howard Hughes Medical Institute, Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095; Department of Biochemistry, University of Wisconsin-Madison, Madison, WI 53706

Journal volume & issue: Vol. 46, no. 1
pp. 123 – 134

Abstract

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Through a positional cloning approach, the thioredoxin-interacting protein gene (Txnip) was recently identified as causal for a form of combined hyperlipidemia in mice (Bodnar, J. S., A. Chatterjee, L. W. Castellani, D. A. Ross, J. Ohmen, J. Cavalcoli, C. Wu, K. M. Dains, J. Catanese, M. Chu, S. S. Sheth, K. Charugundla, P. Demant, D. B. West, P. de Jong, and A. J. Lusis. 2002. Positional cloning of the combined hyperlipidemia gene Hyplip1. Nat. Genet. 30: 110–116). We now show that Txnip-deficient mice in the fed state exhibit a metabolic profile similar to fasted mice, including increased levels of plasma ketone bodies and free fatty acids, decreased glucose, and increased hepatic expression of peroxisome proliferator-activated receptor-γ coactivator-1α, phosphoenolpyruvate carboxykinase, glucose-6-phosphatase, and acyl-CoA oxidase. Dramatic differences in the expression of key metabolic enzymes were also observed in other tissues, and the fat-to-muscle ratio of Txnip-deficient mice was increased by ∼40%. We demonstrate an effect of Txnip on the redox status, as the Txnip-deficient mice in the fed state had a significant increase in the ratio of NADH to NAD+. Surprisingly, we observed that Txnip-deficient mice and wild-type mice had similar levels of thioredoxin activity, suggesting that the effects of Txnip deficiency may be mediated in part by other interactions.These results indicate a role for Txnip in the metabolic response to feeding and the maintenance of the redox status.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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