ArticleMolecular medicine (Cambridge, Mass.)2022
Insulin-inducible THRSP maintains mitochondrial function and regulates sphingolipid metabolism in human adipocytes.
Article in Molecular medicine (Cambridge, Mass.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 21 citations in OpenAlex.
- Pooled it
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- Transcriptome analysis of adipose tissue and muscle of Laiwu and Duroc pigs.Animal nutrition (Zhongguo xu mu shou yi xue hui) · 2024Article
- Associations between OGTT results during pregnancy and offspring TSH levels: a birth cohort study.BMC pregnancy and childbirth · 2024Article
- The identification of a novel shared therapeutic target and drug across all insulin-sensitive tissues under insulin resistance.Frontiers in nutrition · 2024Article
- Identification and functional prediction of lncRNAs associated with intramuscular lipid deposition in Guangling donkeys.Frontiers in veterinary science · 2024Article
- Prognosis and Characterization of Microenvironment in Cervical Cancer Influenced by Fatty Acid Metabolism-Related Genes.Journal of oncology · 2023Article
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThyroid hormone responsive protein (THRSP) is a lipogenic nuclear protein that is highly expressed in murine adipose tissue, but its role in humans remains unknown.
methodsWe characterized the insulin regulation of THRSP in vivo in human adipose tissue biopsies and in vitro in Simpson-Golabi-Behmel syndrome (SGBS) adipocytes. To this end, we measured whole-body insulin sensitivity using the euglycemic insulin clamp technique in 36 subjects [age 40 ± 9 years, body mass index (BMI) 27.3 ± 5.0 kg/m
resultsWe found insulin to increase THRSP mRNA expression 5- and 8-fold after 180 and 360 min of in vivo euglycemic hyperinsulinemia. This induction was impaired in insulin-resistant subjects, and THRSP expression was closely correlated with whole-body insulin sensitivity. In vitro, insulin increased both THRSP mRNA and protein concentrations in SGBS adipocytes in a phosphoinositide 3-kinase (PI3K)-dependent manner. A transcriptomic analysis of THRSP-silenced adipocytes showed alterations in mitochondrial functions and pathways of lipid metabolism, which were corroborated by significantly impaired mitochondrial respiration and fatty acid oxidation. A lipidomic analysis revealed decreased hexosylceramide concentrations, supported by the transcript concentrations of enzymes regulating sphingolipid metabolism.
conclusionsTHRSP is regulated by insulin both in vivo in human adipose tissue and in vitro in adipocytes, and its expression is downregulated by insulin resistance. As THRSP silencing decreases mitochondrial respiration and fatty acid oxidation, its downregulation in human adipose tissue could contribute to mitochondrial dysfunction. Furthermore, disturbed sphingolipid metabolism could add to metabolic dysfunction in obese adipose tissue.
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