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Am J Physiol Cell Physiol. 2019 Aug 14. doi: 10.1152/ajpcell.00051.2019. [Epub ahead of print]

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

Author information

1
Aging and Alzheimers Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, 2139; Faculty of Pharmacy, The University of Sydney, Sydney, 2006; Charles Perkins Centre, The University of Sydney, Sydney, 2006, Australia.
2
Aging and Alzheimers Institute, ANZAC Research Institute, Concord Clinical School/Sydney Medical School, Concord, 2139, Australia; Charles Perkins Centre, The University of Sydney, Sydney, 2006, Australia.
3
Faculty of Pharmacy, The University of Sydney, Sydney, 2006, Australia; UNC Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7569, United States.

Abstract

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 ATPs. 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 co-ordinated to maintain lipid droplet homeostasis and sustain fatty acid β-oxidation during hepatocyte polarization.

KEYWORDS:

bioenergetics; fatty acids; hepatocyte polarization; lipid droplet homeostasis

PMID:
31411916
DOI:
10.1152/ajpcell.00051.2019

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