Cited by 203Diet, Metabolism, and DiseaseMetabolism, Diabetes, and CancerPeroxisome Proliferator-Activated Receptors

The Role of Peroxisome Proliferator-Activated Receptor γ Coactivator-1 β in the Pathogenesis of Fructose-Induced Insulin Resistance

Open access
Nagai, Yoshio, Yonemitsu, Shin, Erion, Derek M., Iwasaki, Takanori, Stark, Romana, Weismann, Dirk, Dong, Jianying, Zhang, Dongyan +10 more·2009·Cell Metabolism

Abstract

Peroxisome proliferator-activated receptor gamma coactivator-1 beta (PGC-1beta) is known to be a transcriptional coactivator for SREBP-1, the master regulator of hepatic lipogenesis. Here, we evaluated the role of PGC-1beta in the pathogenesis of fructose-induced insulin resistance by using an antisense oligonucletoide (ASO) to knockdown PGC-1beta in liver and adipose tissue. PGC-1beta ASO improved the metabolic phenotype induced by fructose feeding by reducing expression of SREBP-1 and downstream lipogenic genes in liver. PGC-1beta ASO also reversed hepatic insulin resistance induced by fructose in both basal and insulin-stimulated states. Furthermore, PGC-1beta ASO increased insulin-stimulated whole-body glucose disposal due to a threefold increase in glucose uptake in white adipose tissue. These data support an important role for PGC-1beta in the pathogenesis of fructose-induced insulin resistance and suggest that PGC-1beta inhibition may be a therapeutic target for treatment of NAFLD, hypertriglyceridemia, and insulin resistance associated with increased de novo lipogenesis.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.cmet.2009.01.011

Cites

42 of 42 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Liver fructose metabolism in the fed state generates lipogenic substrates in an unregulated fashion, driving hepatic de novo lipogenesis and reduced fatty acid oxidation, forming excessive liver fat and inflammation that inactivates insulin signaling, leading to hepatic insulin resistance.

    “For example, liver fructose metabolism in the fed state generates lipogenic substrates in an unregulated fashion, which drives hepatic de novo lipogenesis and reduced fatty acid oxidation, forming excessive liver fat and inflammation that inactivates the insulin signaling pathway, leading to hepatic insulin resistance [16], [17].”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Nagai, Y., Yonemitsu, S., Erion, D. M., Iwasaki, T., Stark, R., Weismann, D., Dong, J., Zhang, D., Jurczak, M. J., Löffler, M. G., Cresswell, J., Yu, X. X., Murray, S. F., Bhanot, S., Monia, B. P., Bogan, J. S., Samuel, V., & Shulman, G. I.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Yale University (US)
  • Ionis Pharmaceuticals (United States) (US)
Corresponding author
Shulman, Gerald I.
Venue
Cell Metabolism
Publisher
Elsevier BV
Published
2009-03
Volume
9
Issue
3
Pages
252-264
ISSN
1550-4131 (ISSN-L)
OpenAlex
W2063518484
Cited by
203
References
42
Citations by year
2026: 3 · 2025: 2 · 2024: 7 · 2023: 9 · 2022: 9 · 2021: 15 · 2020: 6 · 2019: 10 · 2018: 9 · 2017: 11 · 2016: 13 · 2015: 19 · 2014: 15 · 2013: 14 · 2012: 21
FWCI
14.81
Type
journal article
Language
en
Open access
Locations
  • Cell Metabolism (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • Howard Hughes Medical Institute
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK45735, R01-DK40936, R01DK040936, U24DK059635, R01DK075772, R24DK085638, P30DK045735)
  • National Center for Research Resources (K23RR017404, K23 RR-17404)
Topics
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
PGC-1β, fructose-induced insulin resistance, SREBP1, hepatic lipogenesis, antisense oligonucleotide knockdown, hepatic insulin resistance, glucose disposal, non-alcoholic fatty liver disease, hypertriglyceridemia, de novo lipogenesis, liver, adipose tissue
MeSH terms
Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adipose Tissue, Animals, Diet, Fructose, Humans, Insulin Resistance, Liver, Male, Transcription Factors, Gene Expression, Oligonucleotides, Antisense, RNA-Binding Proteins, Rats, Sprague-Dawley, Hepatocytes, Mice, Rats, Sterol Regulatory Element Binding Protein 1

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review