Lipid Droplets and Cellular Lipid Metabolism

Walther, Tobias C.; Farese, Robert V.

doi:10.1146/annurev-biochem-061009-102430

Cited by 1,394 publications

(1,260 citation statements)

References 165 publications

(212 reference statements)

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“…Because the LD membrane is not a bilayer, stably associated transmembrane proteins are not a feature of this organelle. Instead, LD‐linked proteins are found to associate through alternative mechanisms (i.e., lipid modifications, hairpin loops, or amphipathic helices4). Numerous proteomic studies have shown that a significant number of Rab family members are consistently associated with the LD monolayer,5, 6, 40, 41, 42, 43, 44 likely through interactions occurring though C‐terminal prenylation sites.…”

Section: Discussionmentioning

confidence: 99%

“…In most cells, neutral lipids (i.e., triglycerides and cholesterol esters) and fat‐soluble vitamins are sequestered within a specialized storage organelle, the lipid droplet (LD) 4. These unique cytoplasmic structures are thought to be derived from the endoplasmic reticulum and comprise a lipid‐enriched core enclosed within a phospholipid monolayer.…”

Section: Introductionmentioning

confidence: 99%

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Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Schulze¹,

Rasineni

Weller³

et al. 2017

Hepatology Communications

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Alcohol consumption is a well‐established risk factor for the onset and progression of fatty liver disease. An estimated 90% of heavy drinkers are thought to develop significant liver steatosis. For these reasons, an increased understanding of the molecular basis for alcohol‐induced hepatic steatosis is important. It has become clear that autophagy, a catabolic process of intracellular degradation and recycling, plays a key role in hepatic lipid metabolism. We have shown that Rab7, a small guanosine triphosphatase known to regulate membrane trafficking, acts as a key orchestrator of hepatocellular lipophagy, a selective form of autophagy in which lipid droplets (LDs) are specifically targeted for turnover by the autophagic machinery. Nutrient starvation results in Rab7 activation on the surface of the LD and lysosomal compartments, resulting in the mobilization of triglycerides stored within the LDs for energy production. Here, we examine whether the steatotic effects of alcohol exposure are a result of perturbations to the Rab7‐mediated lipophagic pathway. Rats chronically fed an ethanol‐containing diet accumulated significantly higher levels of fat in their hepatocytes. Interestingly, hepatocytes isolated from these ethanol‐fed rats contained juxtanuclear lysosomes that exhibited impaired motility. These changes are similar to those we observed in Rab7‐depleted hepatocytes. Consistent with these defects in the lysosomal compartment, we observed a marked 80% reduction in Rab7 activity in cultured hepatocytes as well as a complete block in starvation‐induced Rab7 activation in primary hepatocytes isolated from chronic ethanol‐fed animals. Conclusion: A mechanism is supported whereby ethanol exposure inhibits Rab7 activity, resulting in the impaired transport, targeting, and fusion of the autophagic machinery with LDs, leading to an accumulation of hepatocellular lipids and hepatic steatosis. (Hepatology Communications 2017;1:140‐152)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Schulze¹,

Rasineni

Weller³

et al. 2017

Hepatology Communications

View full text Add to dashboard Cite

show abstract

“…As excessive free fatty acids are toxic for the cell [1], their esterification into triacylglycerol (TAG) and accumulation within intracellular lipid droplets (LDs) provides a controllable mechanism to buffer and store releasable energy in an inert form [2]. Once considered passive accumulators of fat, LDs are now emerging as dynamic organelles playing a central role in the regulation of lipid metabolism [3].…”

Section: Introductionmentioning

confidence: 99%

Lipid droplet growth: regulation of a dynamic organelle

Barneda

Christian

2017

Current Opinion in Cell Biology

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Intracellular lipid droplets (LDs) are remarkably dynamic and complex organelles that enact regulated storage and release of lipids to fulfil their fundamental roles in energy metabolism, membrane synthesis and provision of lipid-derived signaling molecules.Although small LDs are observed in all types of eukaryotic cells, it is adipocytes that present the widest range of sizes up to the massive unilocular droplet of a white adipocyte. Our knowledge of the proteins and associated processes that control LD dynamics is improving. The dynamic expression of LD-associated proteins is vital for controlling LD biology and is most apparent during adipocyte differentiation. Recent findings on the molecular mechanisms of lipid droplet enlargement reveal the importance of distinct functional groups of proteins and phospholipids.Highlights (max 5 points 85 characters each) Lipid droplet fusion involves major changes in the LD membrane components.Phosphatidic Acid is a key regulator of LD dynamics.Adipocyte differentiation invokes profound regulation of lipid droplet proteins.Transitions between white and BRITE adipocytes require lipid droplet remodelling.

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“…72 It was recently proposed that AQP10 may be an alternative pathway for glycerol efflux in human adipocytes 73 and AQP11, located intracellularly mainly in the endoplasmic reticulum and periphery of lipid storage droplets, an intracellular gateway for glycerol from the lipid stores in human adipocytes. 74 To date, the role of glycerol transport by AQP10 and AQP11 in cell proliferation has not been investigated.…”

Section: Glycerolmentioning

confidence: 99%

Role of aquaporins in cell proliferation: What else beyond water permeability?

2016

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In addition to the extensive data demonstrating the importance of mammalian AQPs for the movement of water and some small solutes across the cell membrane, there is now a growing body of evidence indicating the involvement of these proteins in numerous cellular processes seemingly unrelated, at least some of them in a direct way, to their canonical function of water permeation. Here, we have presented a broad range of evidence demonstrating that these proteins have a role in cell proliferation by various different mechanisms, namely, by allowing fast cell volume regulation during cell division; by affecting progression of cell cycle and helping maintain the balance between proliferation and apoptosis, and by crosstalk with other cell membrane proteins or transcription factors that, in turn, modulate progression of the cell cycle or regulate biosynthesis pathways of cell structural components. In the end, however, after discussing all these data that strongly support a role for AQPs in the cell proliferation process, it remains impossible to conclude that all these other functions attributed to AQPs occur completely independently of their water permeability, and there is a need for new experiments designed specifically to address this interesting issue.

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Lipid Droplets and Cellular Lipid Metabolism

Cited by 1,394 publications

References 165 publications

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Ethanol exposure inhibits hepatocyte lipophagy by inactivating the small guanosine triphosphatase Rab7

Lipid droplet growth: regulation of a dynamic organelle

Role of aquaporins in cell proliferation: What else beyond water permeability?

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