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Perilipin 5 Phosphorylation is Dispensable for Upregulation of Hepatic Lipid Metabolism Genes upon Fasting but Required for Insulin Receptor Substrate 2 Expression in Male Mice
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Perilipin 5 Phosphorylation is Dispensable for Upregulation of Hepatic Lipid Metabolism Genes upon Fasting but Required for Insulin Receptor Substrate 2 Expression in Male Mice

Corinne Bovee, Ryan Grandgenett, Michelle Trevino, Sucharita Dutta, Spencer Peachee, Shayla Kopriva, Farakh Haider, Siming Liu, Gourav Bhardwaj, Christie Penniman, …
bioRxiv
Cold Spring Harbor Laboratory Press
11/09/2024
DOI: 10.1101/2024.11.09.622792
PMCID: PMC11581033
PMID: 39574625
url
https://doi.org/10.1101/2024.11.09.622792View
Preprint (Author's original) This preprint has not been evaluated by subject experts through peer review. Preprints may undergo extensive changes and/or become peer-reviewed journal articles. Open Access

Abstract

Objective Perilipin 5 (PLIN5) is a lipid droplet protein highly expressed in cells that actively oxidize fatty acids. Previous in vitro studies have revealed that PLIN5 phosphorylation (p-PLIN5) at serine 155 by PKA is critical for transcriptional regulation of PPARa target genes by which PLIN5 adapt cells for fatty acid oxidation. We aim to determine the extent of p-PLIN5 in vivo and the consequence of impaired PLIN5 phosphorylation in the liver by using a whole-body knock-in of phosphorylation resistant PLIN5 (SA/SA) in mice. Methods We measured PLIN5 and p-PLIN5 with mass spectrometry and Phos-tag gels. We assessed serum chemistry in WT and SA/SA mice upon fasting. RNA sequencing and qPCR compared the gene expression in the liver of SA/SA and WT mice after overnight fast. Results Plin5 phosphorylation at S155 was increased in the liver LD fraction of fasted mice compared with that of fed mice by mass spectrometry (p<0.05). qPCR of key lipid metabolism genes did not differ between WT and SA/SA liver upon fasting. Male SA/SA mice had a higher fasting blood glucose (p<0.05) without a difference in body weight, serum insulin, or serum lipids. IRS2 was reduced in the liver of fasted male SA/SA mice (p<0.05). Conclusion: PLIN5 S155 phosphorylation is dispensable for the upregulation of lipid metabolism genes important for fasting response in vivo. Impaired phosphorylation also had little effect on serum lipids or liver TG. However, SA/SA mice showed decreased IRS2 expression in the liver, which may contribute to glucose intolerance in SA/SA male mice.Competing Interest StatementThe authors have declared no competing interest.
 Gene Expression Gene Regulation Insulin Lipid Metabolism Mass Spectrometry Metabolism Phosphorylation Scientific Imaging Body weight Fatty acids Glucose metabolism Glucose tolerance Lipids Liver Mass spectroscopy Protein turnover Serum lipids Up-regulation

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