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Cited by 28Liver Disease Diagnosis and TreatmentLipid metabolism and disordersLipid metabolism and biosynthesis

The hepatic lipidome and HNF4α and SHBG expression in human liver

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Winters, Stephen J, Scoggins, Charles R, Appiah, Duke, Ghooray, Dushan T·2020·Endocrine Connections
DOI 10.1530/ec-20-0401PMC PMC7576643
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Abstract

Low plasma levels of sex hormone-binding globulin (SHBG) are a marker for obesity, insulin resistance, non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes. The transcription factor HNF4α is a major determinant of hepatic SHBG expression and thereby serum SHBG levels, and mediates in part the association of low SHBG with hyperinsulinemia and hepatic steatosis. We analyzed the lipidome in human liver specimens from a cohort of patients who underwent hepatic resection as a treatment for cancer, providing insight into hepatic lipids in those without extreme obesity or the clinical diagnosis of NAFLD or non-alcoholic steatohepatitis. Both steatosis and high HOMA-IR were associated with higher levels of saturated and unsaturated FA, other than arachidonic, with the most dramatic rise in 18:1 oleate, consistent with increased stearoyl-CoA desaturase activity. Individuals with low HOMA-IR had low levels of total hepatic fatty acids, while both low and high fatty acid levels characterized the high HOMA-IR group. Both insulin resistance and high levels of hepatic fat were associated with low expression levels of HNF4α and thereby SHBG, but the expression of these genes was also low in the absence of these determinants, implying additional regulatory mechanisms that remain to be determined. The relationship of all FA studied to HNFα and SHBG mRNAs was inverse, and similar to that for total triglyceride concentrations, irrespective of chain length and saturation vs unsaturation.

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Authors
Winters, S. J., Scoggins, C. R., Appiah, D., & Ghooray, D. T.
Affiliations
  • University of Louisville (US)
  • Texas Tech University (US)
Corresponding author
Winters, Stephen J
ORCID
Venue
Endocrine Connections
Publisher
Bioscientifica
Published
2020-10
Volume
9
Issue
10
Pages
1009-1018
ISSN
2049-3614 (ISSN-L)
DOI
10.1530/ec-20-0401
PMC
PMC7576643
OpenAlex
W3087841994
Cited by
28
References
7
Citations by year
2026: 8 · 2025: 5 · 2024: 5 · 2023: 5 · 2022: 2 · 2021: 3
FWCI
1.79
Type
journal article
Language
en
Open access
Locations
  • Endocrine Connections (publishedVersion)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
Jacobs Foundation
Topics
  • Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Lipid metabolism and biosynthesis
Keywords
hepatic lipidome, HNF4α, sex hormone-binding globulin, insulin resistance, hepatic steatosis, fatty acids, stearoyl-CoA desaturase, oleate, HOMA-IR, non-alcoholic fatty liver disease, triglycerides, gene expression, human liver

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