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#lipid droplets

3 public questions tagged with this topic.

Glycolipid and Phospholipid

Which molecule enhances cholesterol storage in lipid droplets?

Neutral lipid storage avoiding lipotoxicity requires chemical conversion free cholesterol hydrophobic ester for sequestration in droplets. ACAT SOAT enzymes ER catalyze transfer oleate oleoyl CoA three beta hydroxyl cholesterol forming cholesteryl oleate no polar head logP about fifteen versus cholesterol logP eight increasing hydrophobicity dramatically. Completely apolar molecule partitions oil phase lipid droplet core together triacylglycerol lens that buds droplet surrounded phospholipid monolayer perilipins PLIN. Esterification sequesters cholesterol away regulatory ER pool sensed SCAP INSIG SREBP preventing ER stress unfolded protein response apoptosis. Hydrolysis NCEH1 LIPE hormone sensitive lipase restores free cholesterol membrane repair steroidogenesis bile acid synthesis liver intestine. Sphingomyelin phosphatidylserine phosphatidylethanolamine remain membrane phospholipids amphipathic heads not stored neutral oil core. Excess cholesteryl ester accumulation macrophages via ACAT1 produces foam cells hallmark atherosclerosis plaques tendon xanthomas familial hypercholesterolemia leading myocardial infarction stroke. Understanding ester storage links cholesterol homeostasis metabolic disease pathobiology therapeutic targeting avasimibe ACAT inhibitors lipid droplet biology core cell biology cardiovascular pathology questions for exams and clinical correlations hyperlipidemia management.

Ref: Chang TY et al., Annu Rev Cell Dev Biol 2006, Cholesterol esterification ACAT storage lipid droplets and foam cells.

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Glycolipid and Phospholipid

Which enzyme aids in lipid droplet formation?

Controlled nucleation lipid droplets depends ER resident seipin protein encoded BSCL2 mutated Berardinelli Seip congenital lipodystrophy type two characterized absence subcutaneous fat severe insulin resistance hypertriglyceridemia hepatic steatosis cardiomyopathy. Cryo EM recent shows seipin decameric ring ten transmembrane helices luminal beta sandwich domains binding anionic phospholipids phosphatidic acid phosphatidylinositol enriching TAG condensation ER junctions LD biogenesis sites demarcated by Pex30. Seipin cooperates LDAF1 LD assembly factor defining droplet biogenesis site facilitates neutral lipid flow ER membrane into lens prevents ectopic lens formation aberrant budding instability. Without seipin cells accumulate numerous tiny droplets clustered perinuclearly or occasional supersized droplets due unstable surface tension unregulated coalescence impaired maturation. Phospholipases hydrolyze phospholipids proteases degrade proteins kinases phosphorylate substrates none orchestrate lens budding efficiently. Yeast homolog Sei1 Fld1 interacts Pex30 Ldb16 Ldo45 controlling ER LD contacts size. Understanding seipin explains how droplet size number controlled metabolically linking ER morphology adipogenesis metabolic syndrome pathology tested advanced cell biology clinical genetics questions concerning organelle biogenesis lipid storage regulation adipose tissue development and therapeutic implications for lipodystrophy treatment strategies emerging.

Ref: Sui et al., Nature 2018, Structure function seipin oligomer lipid droplet formation mechanism and lipodystrophy.

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Glycolipid and Phospholipid

Which statement about lipid droplets is correct?

Lipid droplets defy classic bilayer vesicle definition possessing neutral core surrounded by monolayer explaining unique buoyancy density microscopy appearance. Emergence begins when DGAT1 DGAT2 synthesize triacylglycerol DAG acyl CoA ACAT1 ACAT2 forms cholesteryl ester accumulating between ER leaflets forming oil lens twenty to sixty nanometers growing via Ostwald ripening coalescence regulated Seipin LDAF1 perilipin recruitment. Lens buds toward cytosol coated phospholipid monolayer enriched PC PE lyso PC preventing coalescence decorated perilipin family PLIN1 five CIDE proteins Seipin Rab18 regulating lipolysis contacts mitochondria peroxisomes for beta oxidation fatty acid exchange energy provision. Function storing energy five kilocalories per gram sequestering toxic free fatty acids cholesterol preventing lipotoxic ER stress unfolded protein response providing precursors membrane synthesis eicosanoids prostaglandins. Mobilization ATGL PNPLA2 HSL LIPA lipases and lipophagy via Rab7 LC3 autophagy. They contain hundreds associated proteins contrary protein free notion and do not produce ATP via oxidative phosphorylation which occurs mitochondria matrix. Understanding monolayer architecture explains why droplets float density gradients expand obesity metabolic syndrome nonalcoholic fatty liver disease pathology and diabetes insulin resistance cellular metabolism context for biomedical exams.

Ref: Walther TC & Farese RV, Annu Rev Biochem 2012, Lipid droplets neutral lipid storage monolayer organization and functions.

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