The role of caveolin1 in palmitic acid-induced hepatic steatosis

doi:10.3877/cma.j.issn.2095-9605.2019.01.003

Abstract

Abstract:

Objective

To explore the role of caveolin1 in palmitic acid (PA)-induced hepatic steatosis.

Methods

Stable caveolin1 (CAV1) overexpressing HepG2 cells were developed by transfection with lentiviral particles containing human CAV1 protein (Lenti-CAV1). Lenti-Control served as a negative control. After 24 hours fatty acid free bovine serum albumin (BSA) and PA incubation, lipid deposition was determined by Oil red staining and cellular triglyceride was measured. Real time PCR was used to detect the mRNA expression of PGC1α and sirt3.

Results

Compared with BSA treatment, PA treatment for 24 hours increased the lipid droplets and triglyceride content (P<0.01). Compared with negative control, overexpression of caveolin1 attenuated the accumulation of lipid droplets and triglyceride content in HepG2 cells (P<0.05) . At the same time , the mRNA expression of PGC1α and sirt3 were increased in CAV1 overexpressing cells (P<0.05).

Conclusions

Caveolin1 may improve PA-induced hepatic steatosis through up-regulating PGC1α-sirt3 axis.

Key words: NAFLD, Caveolin1, PGC1α, Sirt3

Chuwen Lin, Wen Zeng, Shuo Lin, Kunying Liu, Fen Xu, Hua Liang, Longyi Zeng. The role of caveolin1 in palmitic acid-induced hepatic steatosis[J]. Chinese Journal of Obesity and Metabolic Diseases(Electronic Edition), 2019, 05(01): 15-19.

/ / Recommend

Add to citation manager EndNote|Ris|BibTeX

URL: https://zhfpydxbdzzz.cma-cmc.com.cn/EN/10.3877/cma.j.issn.2095-9605.2019.01.003

https://zhfpydxbdzzz.cma-cmc.com.cn/EN/Y2019/V05/I01/15

Figures/Tables 5

References 25

[1]	Rinella M, Charlton M. The globalization of nonalcoholic fatty liver disease: Prevalence and impact on world health[J]. Hepatology, 2016, 64(1):19-22.
[2]	Festi D, Colecchia A, Sacco T, et al. Hepatic steatosis in obese patients: clinical aspects and prognostic significance[J]. Obes Rev, 2004, 5(1):27-42.
[3]	Izumi T, Shibata Y, Yamamoto T. The cytoplasmic surface structures of uncoated vesicles in various tissues of rat as revealed by quick-freeze, deep-etching replicas[J]. J Electron Microsc (Tokyo), 1989, 38(1):47-53.
[4]	Kim CA, Delepine M, Boutet E, et al. Association of a homozygous nonsense caveolin-1 mutation with Berardinelli-Seip congenital lipodystrophy[J]. J Clin Endocrinol Metab, 2008, 93(4):1129-1134.
[5]	Cohen AW, Razani B, Wang XB, et al. Caveolin-1-deficient mice show insulin resistance and defective insulin receptor protein expression in adipose tissue[J]. Am J Physiol Cell Physiol, 2003, 285(1):C222-C235.
[6]	Baudrand R, Gupta N, Garza A E, et al. Caveolin 1 Modulates Aldosterone-Mediated Pathways of Glucose and Lipid Homeostasis[J]. J Am Heart Assoc, 2016, 5(10):e003845.
[7]	Li M, Chen D, Huang H, et al. Caveolin1 protects against diet induced hepatic lipid accumulation in mice[J]. PLoS One, 2017, 12(6):e178748.
[8]	Pojoga LH, Underwood PC, Goodarzi MO, et al. Variants of the caveolin-1 gene: a translational investigation linking insulin resistance and hypertension[J]. J Clin Endocrinol Metab, 2011, 96(8):E1288-E1292.
[9]	PALADE GE. An electron microscope study of the mitochondrial structure[J]. J Histochem Cytochem, 1953, 1(4):188-211.
[10]	Li B, Zhang Z, Zhang H, et al. Aberrant miR199a-5p/caveolin1/PPARalpha axis in hepatic steatosis[J]. J Mol Endocrinol, 2014, 53(3):393-403.
[11]	Yoneda M, Hotta K, Nozaki Y, et al. Association between PPARGC1A polymorphisms and the occurrence of nonalcoholic fatty liver disease (NAFLD)[J]. BMC Gastroenterol, 2008, 8(1):27.
[12]	Adiels M, Taskinen MR, Boren J. Fatty liver, insulin resistance, and dyslipidemia[J]. Curr Diab Rep, 2008, 8(1):60-64.
[13]	Aharoni-Simon M, Hann-Obercyger M, Pen S, et al. Fatty liver is associated with impaired activity of PPARgamma-coactivator 1alpha (PGC1alpha) and mitochondrial biogenesis in mice[J]. Lab Invest, 2011, 91(7):1018-1028.
[14]	Estall JL, Kahn M, Cooper MP, et al. Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-gamma coactivator-1alpha expression[J]. Diabetes, 2009, 58(7):1499-1508.
[15]	Louet JF, Hayhurst G, Gonzalez FJ, et al. The coactivator PGC-1 is involved in the regulation of the liver carnitine palmitoyltransferase I gene expression by cAMP in combination with HNF4 alpha and cAMP-response element-binding protein (CREB)[J]. J Biol Chem, 2002, 277(41):37991-38000.
[16]	Vega RB, Huss JM, Kelly DP. The coactivator PGC-1 cooperates with peroxisome proliferator-activated receptor alpha in transcriptional control of nuclear genes encoding mitochondrial fatty acid oxidation enzymes[J]. Mol Cell Biol, 2000, 20(5):1868-1876.
[17]	Schwer B, North B J, Frye R A, et al. The human silent information regulator (Sir)2 homologue hSIRT3 is a mitochondrial nicotinamide adenine dinucleotide-dependent deacetylase[J]. J Cell Biol, 2002, 158(4):647-657.
[18]	张爽，朱晓辉，卢新, 等. 非酒精性脂肪性肝病风险基因SIRT3的关联验证和体内过表达效应研究[J]. 第三军医大学学报, 2017(08):737-742.
[19]	Hirschey MD, Shimazu T, Jing E, et al. SIRT3 deficiency and mitochondrial protein hyperacetylation accelerate the development of the metabolic syndrome[J]. Mol Cell, 2011, 44(2):177-190.
[20]	Hirschey MD, Shimazu T, Goetzman E, et al. SIRT3 regulates mitochondrial fatty-acid oxidation by reversible enzyme deacetylation[J]. Nature, 2010, 464(7285):121-125.
[21]	Lu Z, Chen Y, Aponte A M, et al. Prolonged fasting identifies heat shock protein 10 as a Sirtuin 3 substrate: elucidating a new mechanism linking mitochondrial protein acetylation to fatty acid oxidation enzyme folding and function[J]. J Biol Chem, 2015, 290(4):2466-2476.
[22]	Dittenhafer-Reed KE, Richards AL, Fan J, et al. SIRT3 mediates multi-tissue coupling for metabolic fuel switching[J]. Cell Metab, 2015, 21(4):637-646.
[23]	Cho EH. SIRT3 as a Regulator of Non-alcoholic Fatty Liver Disease[J]. J Lifestyle Med, 2014, 4(2):80-85.
[24]	Shi T, Fan GQ, Xiao SD. SIRT3 reduces lipid accumulation via AMPK activation in human hepatic cells[J]. J Dig Dis, 2010, 11(1):55-62.
[25]	Kong X, Wang R, Xue Y, et al. Sirtuin 3, a new target of PGC-1alpha, plays an important role in the suppression of ROS and mitochondrial biogenesis[J]. PLoS One, 2010, 5(7):e11707.

基因	上游引物（5'→3’）	下游引物（5'→3’）
β-actin	ACAGAGCCTCGCCTTTGCCGAT	CTTGCACATGCCGGAGCCGTT
PGC1α	TCTGAGTCTGTATGGAGTGACAT	CCAAGTCGTTCACATCTAGTTCA
Sirt3	ACCCAGTGGCATTCCAGAC	GGCTTGGGGTTGTGAAAGAAG

基因	上游引物（5'→3’）	下游引物（5'→3’）
β-actin	ACAGAGCCTCGCCTTTGCCGAT	CTTGCACATGCCGGAGCCGTT
PGC1α	TCTGAGTCTGTATGGAGTGACAT	CCAAGTCGTTCACATCTAGTTCA
Sirt3	ACCCAGTGGCATTCCAGAC	GGCTTGGGGTTGTGAAAGAAG

Please choose a citation manager

Content to export