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Is hepatic lipogenesis fundamental for NAFLD/NASH? A focus on the nuclear receptor coactivator PGC-1β

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Abstract

Non-alcoholic fatty liver diseases are the hepatic manifestation of metabolic syndrome. According to the classical pattern of NAFLD progression, de novo fatty acid synthesis has been incriminated in NAFLD progression. However, this hypothesis has been challenged by the re-evaluation of NAFLD development mechanisms together with the description of the role of lipogenic genes in NAFLD and with the recent observation that PGC-1β, a nuclear receptor/transcription factor coactivator involved in the transcriptional regulation of lipogenesis, displays protective effects against NAFLD/NASH progression. In this review, we focus on the implication of lipogenesis and triglycerides synthesis on the development of non-alcoholic fatty liver diseases and discuss the involvement of these pathways in the protective role of PGC-1β toward these hepatic manifestations.

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Abbreviations

NAFLD:

Non-alcoholic fatty liver diseases

FA:

Fatty acid

TG:

Triglycerides

PGC-1β:

Peroxisome proliferator-activated receptor gamma coactivator 1β

LXR:

Liver X receptor

SREBP-1c:

Sterol regulatory element binding protein 1c

ChREBP:

Carbohydrate responsive element binding protein

MCD:

Methionine/choline deficient diet

HFD:

High fat diet

NASH:

Non alcoholic steatohepatitis

NPC1L1:

Niemann–Pick C1-like 1

HSC:

Hepatic stellate cell

TNFα:

Tumor necrosis factor α

TGF-1β:

Transforming growth factor-1 β

COL1A1:

Collagen type 1α1

α-SMA:

α-Smooth muscle actin

TLR:

Toll-like receptor

PAMP:

Pathogen-associated molecular patterns

DAMP:

Damage-associated molecular patterns

HMGB1:

High mobility group box 1

ROS:

Reactive oxygen species

CPT1:

Carnitine palmitoyl transferase 1

mtDNA:

Mitochondrial DNA

ACL:

ATP citrate lyase

ACC:

Acetyl-CoA carboxylase

FAS:

Fatty acid synthase

ELOVL:

Elongation of very long chain fatty acids proteins

SCD1:

Stearoyl-CoA desaturase 1

GPAT:

Glycerol-3-phosphate acyl transferase

LPA:

Lysophosphatidic acid

PA:

Phosphatidic acid

AGPAT:

1-Acylglycerol-3-phosphate acyltransferase

DGAT:

Diacylglycerol acyltransferase

PRC:

PGC-1-related coactivator

NRF-2:

Nuclear respiratory factor-2

PPARα:

Peroxisome proliferator-activated receptor α

FoxO2:

Forkhead box O2

VLDL:

Very low-density lipoprotein

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Acknowledgments

We apologize to our distinguished colleagues whose work has not been cited owing to space limitations.

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Authors and Affiliations

  1. Clinica Medica “Cesare Frugoni”, Department of Interdisciplinary Medicine, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124, Bari, Italy

    Simon Ducheix, Maria Carmela Vegliante, Nicola Napoli, Carlo Sabbà & Antonio Moschetta

  2. IRCCS Istituto Tumori “Giovanni Paolo II”, Viale O. Flacco 65, 70124, Bari, Italy

    Simon Ducheix & Antonio Moschetta

  3. Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro”, Piazza Giulio Cesare 11, 70124, Bari, Italy

    Gaetano Villani

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  1. Simon Ducheix
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  2. Maria Carmela Vegliante
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  3. Gaetano Villani
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Correspondence to Antonio Moschetta.

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This work was funded by the Italian Ministry of University and Education (PRIN 2010FHH32M-002), the Italian Ministry of Health (Young Researchers Grant GR-2010-2314703), and Fondazione Umberto Veronesi (FUV).

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Ducheix, S., Vegliante, M.C., Villani, G. et al. Is hepatic lipogenesis fundamental for NAFLD/NASH? A focus on the nuclear receptor coactivator PGC-1β. Cell. Mol. Life Sci. 73, 3809–3822 (2016). https://doi.org/10.1007/s00018-016-2331-x

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  • DOI: https://doi.org/10.1007/s00018-016-2331-x

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