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Lipid metabolism, inflammation, and foam cell formation in health and metabolic disorders: targeting mTORC1

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Abstract

Metabolic homeostasis is important for maintaining a healthy lifespan. Lipid metabolism is particularly necessary for the maintenance of metabolic energy sources and their storage, and the structure and function of cell membranes, as well as for the regulation of nutrition through lipogenesis, lipolysis, and lipophagy. Dysfunctional lipid metabolism leads to the development of metabolic disorders, such as atherosclerosis, diabetes mellitus, and non-alcoholic fatty liver disease (NAFLD). Furthermore, dyslipidaemia causes inflammatory responses and foam cell formation. Mechanistic target of rapamycin (mTOR) signalling is a key regulator of diverse cellular processes, including cell metabolism and cell fate. mTOR complex 1 (mTORC1) is involved in lipid metabolism and immune responses in the body. Therefore, the mTORC1 signalling pathway has been suggested as a potential therapeutic target for the treatment of metabolic disorders. In this review, we focus on the roles of mTORC1 in lipid metabolism and inflammation, and present current evidence on its involvement in the development and progression of metabolic disorders.

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Abbreviations

mTOR:

Mechanistic target of rapamycin

mTORC1:

MTOR complex 1

PI3K:

Phosphoinositide 3-kinase

PIKK:

PI3K-related kinase

Raptor:

Regulatory protein associated with mTOR

mLST8:

Mammalian lethal with Sec13 protein 8

Deptor:

Dishevelled, Egl-10 and pleckstrin (DEP)–domain-containing mTOR-interacting protein

PRAS40:

Proline-rich AKT substrate 40 kDa

Rictor:

Rapamycin-insensitive companion of mTOR

Protor-1:

Protein observed with Rictor-1

mSIN1:

Mammalian stress-activated protein kinase interacting protein

S6K:

P70 ribosomal S6 kinase

4E-BP1:

Eukaryotic translation initiation factor 4E (eIF4E)–binding protein 1

NAFLD:

Non-alcoholic fatty liver disease

TCA:

Tricarboxylic acid

ACLY:

Acetyl-CoA by ATP citrate lyase

ACC:

Acetyl-CoA carboxylase

FASN:

Fatty acid synthase

SCD:

Stearoyl CoA desaturase

VLDLs:

Very low density lipoproteins

HMGCS:

3-Hydroxy-3-methylglutaryl acetyl-CoA (HMG-CoA) synthase

HMGCR:

HMG-CoA reductase

SREBP:

Sterol regulatory element–binding protein

JMJD1C:

Jumonji domain–containing 1C

LXR:

Liver X receptor

USF-1:

Upstream transcription factor 1

PPAR:

Peroxisome proliferator-activated receptor

C/EBP:

CCAAT/enhancer-binding protein

ATGL:

Adipose triglyceride lipase

HSL:

Hormone-sensitive lipase

TFEB:

Transcription factor EB

IL:

Interleukin

TNF-α:

Tumour necrosis factor α

HIF-1α:

Hypoxia-inducible factor 1α

MGL-1:

Macrophage galactose-type lectin 1

TGF:

Transforming growth factor

STAT6:

Signal transducer and activator of transcription 6

LOX1:

Lectin-type oxidised low-density lipoprotein receptor 1

SR-A:

Scavenger receptor-A

HDL:

High-density lipoprotein

ABCA1:

ATP-binding cassette transporter A family member 1

ABCG1:

ATP-binding cassette subfamily G member 1

CXCL1:

Chemokine (CXC motif) ligand 1

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Funding

This study was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIT) (No. 2020R1C1C1010613) to So Yeong Cheon and the Basic Science Research Program through the NRF grant funded by the Ministry of Education (NRF-2018R1D1A1B07048587) to KyoungJoo Cho.

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  1. Department of Biotechnology, College of Biomedical & Health Science, Konkuk University, Chungju, Republic of Korea

    So Yeong Cheon

  2. Department of Life Science, College of Science and Engineering, Kyonggi University, Gwanggyosan-ro, Yeongtong-gu, Suwon, Gyeonggi-do, 16227, Republic of Korea

    KyoungJoo Cho

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  1. So Yeong Cheon
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S.Y.C. designed this study and wrote the manuscript. K.J.C. and S.Y.C. prepared figures and figure legends. K.J.C. and S.Y.C. edited the manuscript. K.J.C. finalised the revised manuscript. All the authors read and approved the final version of this manuscript.

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Cheon, S.Y., Cho, K. Lipid metabolism, inflammation, and foam cell formation in health and metabolic disorders: targeting mTORC1. J Mol Med 99, 1497–1509 (2021). https://doi.org/10.1007/s00109-021-02117-8

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