Regulation of lipid stores and metabolism by lipophagy

K. Liu, M. J. Czaja

Research output: Contribution to journalArticle

200 Citations (Scopus)

Abstract

Intracellular lipids are stored in lipid droplets (LDs) and metabolized by cytoplasmic neutral hydrolases to supply lipids for cell use. Recently, an alternative pathway of lipid metabolism through the lysosomal degradative pathway of autophagy has been described and termed lipophagy. In this form of lipid metabolism, LD triglycerides (TGs) and cholesterol are taken up by autophagosomes and delivered to lysosomes for degradation by acidic hydrolases. Free fatty acids generated by lipophagy from the breakdown of TGs fuel cellular rates of mitochondrial β-oxidation. Lipophagy therefore functions to regulate intracellular lipid stores, cellular levels of free lipids such as fatty acids and energy homeostasis. The amount of lipid metabolized by lipophagy varies in response to the extracellular supply of nutrients. The ability of the cell to alter the amount of lipid targeted for autophagic degradation depending on nutritional status demonstrates that this process is selective. Intracellular lipids themselves regulate levels of autophagy by unclear mechanisms. Impaired lipophagy can lead to excessive tissue lipid accumulation such as hepatic steatosis, alter hypothalamic neuropeptide release to affect body mass, block cellular transdifferentiation and sensitize cells to death stimuli. Future studies will likely identify additional mechanisms by which lipophagy regulates cellular physiology, making this pathway a potential therapeutic target in a variety of diseases.

Original languageEnglish (US)
Pages (from-to)3-11
Number of pages9
JournalCell Death and Differentiation
Volume20
Issue number1
DOIs
StatePublished - Jan 2013

Fingerprint

Lipid Metabolism
Lipids
Autophagy
Hydrolases
Triglycerides
Lysosomes
Neuropeptides
Nutritional Status
Nonesterified Fatty Acids
Homeostasis
Cell Death
Fatty Acids
Cholesterol
Food
Liver

Keywords

  • apoptosis
  • autophagy
  • cholesterol
  • hypothalamus
  • triglycerides

ASJC Scopus subject areas

  • Cell Biology
  • Molecular Biology

Cite this

Regulation of lipid stores and metabolism by lipophagy. / Liu, K.; Czaja, M. J.

In: Cell Death and Differentiation, Vol. 20, No. 1, 01.2013, p. 3-11.

Research output: Contribution to journalArticle

Liu, K. ; Czaja, M. J. / Regulation of lipid stores and metabolism by lipophagy. In: Cell Death and Differentiation. 2013 ; Vol. 20, No. 1. pp. 3-11.
@article{491fb0f7dffe450d83e3a4b76fa48ea7,
title = "Regulation of lipid stores and metabolism by lipophagy",
abstract = "Intracellular lipids are stored in lipid droplets (LDs) and metabolized by cytoplasmic neutral hydrolases to supply lipids for cell use. Recently, an alternative pathway of lipid metabolism through the lysosomal degradative pathway of autophagy has been described and termed lipophagy. In this form of lipid metabolism, LD triglycerides (TGs) and cholesterol are taken up by autophagosomes and delivered to lysosomes for degradation by acidic hydrolases. Free fatty acids generated by lipophagy from the breakdown of TGs fuel cellular rates of mitochondrial β-oxidation. Lipophagy therefore functions to regulate intracellular lipid stores, cellular levels of free lipids such as fatty acids and energy homeostasis. The amount of lipid metabolized by lipophagy varies in response to the extracellular supply of nutrients. The ability of the cell to alter the amount of lipid targeted for autophagic degradation depending on nutritional status demonstrates that this process is selective. Intracellular lipids themselves regulate levels of autophagy by unclear mechanisms. Impaired lipophagy can lead to excessive tissue lipid accumulation such as hepatic steatosis, alter hypothalamic neuropeptide release to affect body mass, block cellular transdifferentiation and sensitize cells to death stimuli. Future studies will likely identify additional mechanisms by which lipophagy regulates cellular physiology, making this pathway a potential therapeutic target in a variety of diseases.",
keywords = "apoptosis, autophagy, cholesterol, hypothalamus, triglycerides",
author = "K. Liu and Czaja, {M. J.}",
year = "2013",
month = "1",
doi = "10.1038/cdd.2012.63",
language = "English (US)",
volume = "20",
pages = "3--11",
journal = "Cell Death and Differentiation",
issn = "1350-9047",
publisher = "Nature Publishing Group",
number = "1",

}

TY - JOUR

T1 - Regulation of lipid stores and metabolism by lipophagy

AU - Liu, K.

AU - Czaja, M. J.

PY - 2013/1

Y1 - 2013/1

N2 - Intracellular lipids are stored in lipid droplets (LDs) and metabolized by cytoplasmic neutral hydrolases to supply lipids for cell use. Recently, an alternative pathway of lipid metabolism through the lysosomal degradative pathway of autophagy has been described and termed lipophagy. In this form of lipid metabolism, LD triglycerides (TGs) and cholesterol are taken up by autophagosomes and delivered to lysosomes for degradation by acidic hydrolases. Free fatty acids generated by lipophagy from the breakdown of TGs fuel cellular rates of mitochondrial β-oxidation. Lipophagy therefore functions to regulate intracellular lipid stores, cellular levels of free lipids such as fatty acids and energy homeostasis. The amount of lipid metabolized by lipophagy varies in response to the extracellular supply of nutrients. The ability of the cell to alter the amount of lipid targeted for autophagic degradation depending on nutritional status demonstrates that this process is selective. Intracellular lipids themselves regulate levels of autophagy by unclear mechanisms. Impaired lipophagy can lead to excessive tissue lipid accumulation such as hepatic steatosis, alter hypothalamic neuropeptide release to affect body mass, block cellular transdifferentiation and sensitize cells to death stimuli. Future studies will likely identify additional mechanisms by which lipophagy regulates cellular physiology, making this pathway a potential therapeutic target in a variety of diseases.

AB - Intracellular lipids are stored in lipid droplets (LDs) and metabolized by cytoplasmic neutral hydrolases to supply lipids for cell use. Recently, an alternative pathway of lipid metabolism through the lysosomal degradative pathway of autophagy has been described and termed lipophagy. In this form of lipid metabolism, LD triglycerides (TGs) and cholesterol are taken up by autophagosomes and delivered to lysosomes for degradation by acidic hydrolases. Free fatty acids generated by lipophagy from the breakdown of TGs fuel cellular rates of mitochondrial β-oxidation. Lipophagy therefore functions to regulate intracellular lipid stores, cellular levels of free lipids such as fatty acids and energy homeostasis. The amount of lipid metabolized by lipophagy varies in response to the extracellular supply of nutrients. The ability of the cell to alter the amount of lipid targeted for autophagic degradation depending on nutritional status demonstrates that this process is selective. Intracellular lipids themselves regulate levels of autophagy by unclear mechanisms. Impaired lipophagy can lead to excessive tissue lipid accumulation such as hepatic steatosis, alter hypothalamic neuropeptide release to affect body mass, block cellular transdifferentiation and sensitize cells to death stimuli. Future studies will likely identify additional mechanisms by which lipophagy regulates cellular physiology, making this pathway a potential therapeutic target in a variety of diseases.

KW - apoptosis

KW - autophagy

KW - cholesterol

KW - hypothalamus

KW - triglycerides

UR - http://www.scopus.com/inward/record.url?scp=84870995648&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84870995648&partnerID=8YFLogxK

U2 - 10.1038/cdd.2012.63

DO - 10.1038/cdd.2012.63

M3 - Article

VL - 20

SP - 3

EP - 11

JO - Cell Death and Differentiation

JF - Cell Death and Differentiation

SN - 1350-9047

IS - 1

ER -