Multiple cellular pathways regulate lipid droplet homeostasis for the establishment of polarity in collagen sandwich-cultured hepatocytes

Hepatocyte polarization is energy dependent. The establishment of polarization in collagen sandwich culture of hepatocytes requires utilization of lipid droplets and mitochondrial β-oxidation to supply ATP. Multiple cellular pathways are involved in lipid droplet homeostasis; however, mechanistic in...

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Bibliographic Details
Published in:American Journal of Physiology: Cell Physiology 2019-11, Vol.317 (5), p.C942-C952
Main Authors: Kang, Sun Woo Sophie, Cogger, Victoria C, Le Couteur, David G, Fu, Dong
Format: Article
Language:English
Subjects:
Animals
Autophagy
Bioenergetics
Cell culture
Cell Polarity - physiology
Cells, Cultured
Cholesterol
Collagen
Collagen - metabolism
Esterification
Fatty acids
Hepatocytes
Hepatocytes - metabolism
Homeostasis
Homeostasis - physiology
Lipid Droplets - metabolism
Lipids
Lipolysis
Male
Mitochondria
Oxidation
Phagocytosis
Polarity
Polarization
Rats
Rats, Sprague-Dawley
Signal Transduction - physiology
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Summary:Hepatocyte polarization is energy dependent. The establishment of polarization in collagen sandwich culture of hepatocytes requires utilization of lipid droplets and mitochondrial β-oxidation to supply ATP. Multiple cellular pathways are involved in lipid droplet homeostasis; however, mechanistic insights of how hepatocytes utilize lipid droplets during polarization remain elusive. The current study investigated the effects of various pathways involved in lipid droplet homeostasis on bioenergetics during hepatocyte polarization. The results showed that hepatocytes were dependent on lipolysis of lipid droplets to release fatty acids for β-oxidation. Inhibition of lipolysis significantly decreased cellular fatty acid and ATP levels and inhibited hepatocyte polarization, revealing that lipolysis was an important mechanism for providing energy for hepatocyte polarization. The results also demonstrated that autophagic degradation of lipid droplets (lipophagy) was not essential for breaking down lipid droplets. Conversely, autophagy contributed to lipid droplet formation and played a key role in sustaining lipid droplet stores for energy production. In addition, cholesterol biosynthesis/cholesterol esterification and de novo fatty acid synthesis also contributed to maintaining lipid droplet stores for bioenergetics during hepatocyte polarization. In summary, multiple cellular pathways are coordinated to maintain lipid droplet homeostasis and sustain fatty acid β-oxidation during hepatocyte polarization.
ISSN:0363-6143
1522-1563
DOI:10.1152/ajpcell.00051.2019