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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2021.9
- 수록면
- 476 - 481 (6page)
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초록· 키워드
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Liver receptor homolog-1 (LRH-1) has emerged as a regulatorof hepatic glucose, bile acid, and mitochondrial metabolism.
However, the functional mechanism underlying the effect ofLRH-1 on lipid mobilization has not been addressed. Thisstudy investigated the regulatory function of LRH-1 in lipidmetabolism in maintaining a normal liver physiological stateduring fasting. The Lrh-1f/f and LRH-1 liver-specific knockout(Lrh-1LKO) mice were either fed or fasted for 24 h, and the liverand serum were isolated. The livers were used for qPCR,western blot, and histological analysis. Primary hepatocyteswere isolated for immunocytochemistry assessments of lipids.
During fasting, the Lrh-1LKO mice showed increased accumulationof triglycerides in the liver compared to that in Lrh-1f/fmice. Interestingly, in the Lrh-1LKO liver, decreases in perilipin5 (PLIN5) expression and genes involved in β-oxidation wereobserved. In addition, the LRH-1 agonist dialauroylphosphatidylcholinealso enhanced PLIN5 expression in human culturedHepG2 cells. To identify new target genes of LRH-1, these findingsdirected us to analyze the Plin5 promoter sequence, whichrevealed ?1620/?1614 to be a putative binding site for LRH-1.
This was confirmed by promoter activity and chromatin immunoprecipitationassays. Additionally, fasted Lrh-1f/f primary hepatocytesshowed increased co-localization of PLIN5 in lipid droplets(LDs) compared to that in fasted Lrh-1LKO primary hepatocytes.
Overall, these findings suggest that PLIN5 might be anovel target of LRH-1 to mobilize LDs, protect the liver fromlipid overload, and manage the cellular needs during fasting.
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참고문헌 (32)
참고문헌 신청
Fayard E / 2004 / LRH-1 : an orphan nuclear receptor involved in development, metabolism and steroidogenesis / Trends Cell Biol 14:250~260
Stein S / 2017 / Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease / J Clin Invest 127:583~592
Schwaderer J / 2020 / Pharmacological LRH-1/Nr5a2 inhibition limits pro-inflammatory cytokine production in macrophages and associated experimental hepatitis / Cell Death Dis 11:154
Holmstrom SR / 2011 / LRH-1and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function / Genes Dev 25:1674~1679
Duggavathi R / 2008 / Liver receptor homolog 1 is essential for ovulation / Genes Dev 22:1871~1876
Stein S / 2017 / Impaired SUMOylation of nuclear receptor LRH-1 promotes nonalcoholic fatty liver disease / J Clin Invest 127:583~592
Schwaderer J / 2020 / Pharmacological LRH-1/Nr5a2 inhibition limits pro-inflammatory cytokine production in macrophages and associated experimental hepatitis / Cell Death Dis 11:154
Holmstrom SR / 2011 / LRH-1and PTF1-L coregulate an exocrine pancreas-specific transcriptional network for digestive function / Genes Dev 25:1674~1679
Duggavathi R / 2008 / Liver receptor homolog 1 is essential for ovulation / Genes Dev 22:1871~1876
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