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Quantitative proteomics analysis reveals glutamine deprivation activates fatty acid β-oxidation pathway in HepG2 cells

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Abstract

Glutamine, a multifunctional amino acid, functions in nutrient metabolism, energy balance, apoptosis, and cell proliferation. Lipid is an important nutrient and controls a broad range of physiological processes. Previous studies have demonstrated that glutamine can affect lipolysis and lipogenesis, but the effect of glutamine on the detailed lipid metabolism remains incompletely understood. Here, we applied the quantitative proteomics approach to estimate the relative abundance of proteins in HepG2 cells treated by glutamine deprivation. The results showed that there were 212 differentially abundant proteins in response to glutamine deprivation, including 150 significantly increased proteins and 62 significantly decreased proteins. Interestingly, functional classification showed that 43 differentially abundant proteins were related to lipid metabolism. Further bioinformatics analysis and western blotting validation revealed that lipid accumulation may be affected by β-oxidation of fatty acid induced by glutamine deprivation in HepG2 cells. Together, our results may provide the potential for regulating lipid metabolism by glutamine in animal production and human nutrition. The MS data have been deposited to the ProteomeXchange Consortium with identifier PXD003387.

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Abbreviations

iTRAQ:

Isobaric tags for relative and absolute quantification

FFAs:

Free fatty acids

TGs:

Triglycerides

LDs:

Lipid droplets

LC–MS/MS:

Liquid chromatography–tandem mass spectrometry

IPA:

Ingenuity pathway analysis

ACSL1:

Long-chain fatty acid acyl-CoA ligase 1

ACOX1:

Peroxisomal acyl-CoA oxidase 1

ACADS:

Short-chain acyl-CoA dehydrogenase

ACAA1:

3-Ketoacyl-CoA thiolase

ADH1C:

Alcohol dehydrogenase 1C

ALDH8A1:

Aldehyde dehydrogenase family 8 member A1

ALDH2:

Mitochondrial aldehyde dehydrogenase 2

DECR1:

2,4-Dienoyl-CoA reductase

TYSND1:

Peroxisomal leader peptide-processing protease

CES1:

Liver carboxylesterase 1

NP2:

Niemann-Pick disease, type C2

SCP2:

Sterol carrier protein 2

DHCR24:

Delta(24)-sterol reductase

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Acknowledgments

We thank all Yan laboratory members and Professor Guoquan Liu for discussions and critical reading of the manuscript. Projects supported by the National Key Basic Research Program of China (973 Program) (No. 2013CB127305), the National Natural Science Foundation of China (No. 31322053 and 31172290), the Hubei Province Distinguished Young Scholar (No. 2012FFA015), Wuhan City Youth Science dawn project (No. 2013070104010018) and the Fundamental Research Funds for the Central Universities (No. 2013PY056 and 2013JQ001).

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Correspondence to Xianghua Yan.

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The authors declare that they have no conflict of interest.

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Handling Editor: P. R. Jungblut.

B. Long and R. Muhamad contributed equally to the present study.

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Long, B., Muhamad, R., Yan, G. et al. Quantitative proteomics analysis reveals glutamine deprivation activates fatty acid β-oxidation pathway in HepG2 cells. Amino Acids 48, 1297–1307 (2016). https://doi.org/10.1007/s00726-016-2182-7

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  • DOI: https://doi.org/10.1007/s00726-016-2182-7

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