Preventing hepatocyte steatosis by co-culture with adipocytes during plasma exposure

Deepak Nagrath, Vanessa Lopez, Francois Berthiaume, Martin Yarmush

Research output: Contribution to conferencePaperpeer-review

Abstract

During bioartificial liver operation when extracorporeal bioartificial liver (BAL) systems (which consists of functioning, viable hepatocytes) are exposed to patient plasma/blood there is an increased accumulation of lipids which in turn leads to deterioration of liver-specific functions. Studies on whole-body metabolism have shown that adipose tissue is the preferential site for lipid storage, and adipocytokines secreted by adipocytes, such as leptin, adiponectin, TNF-a, and resistin, play an important roles in metabolic homeostasis by changing hepatic insulin sensitivity and peroxisomal b-oxidation. We hypothesized that coculturing adipocytes with hepatocytes would improve lipid metabolism and reduce intracellular lipid accumulation in hepatocytes. In coculture configuration, hepatocytes were seeded in a double gel sandwich culture on 6 well dishes and 3T3-L1 preadipocytes were seeded on the inserts and later differentiated into mature adipocytes. The coculture system was modulated for differential activation of fat storage in adipcocytes and catabolism of fatty acids and b-oxidation in hepatocytes through peroxisomal proliferator activated receptor (PPAR) ligands. The results clearly demonstrate that the lipids in plasma were differentially routed to adipocytes, thus preventing the accumulation of excess fat in hepatocytes. Additionally, we modulated the adipokines to increase the hepatic functions. The adiponectin and leptin expression was increased and resistin expression was decreased through PPAR ligands to increase the liver specific functions.

Original languageEnglish (US)
Pages9228
Number of pages1
StatePublished - 2005
Event05AIChE: 2005 AIChE Annual Meeting and Fall Showcase - Cincinnati, OH, United States
Duration: Oct 30 2005Nov 4 2005

Other

Other05AIChE: 2005 AIChE Annual Meeting and Fall Showcase
Country/TerritoryUnited States
CityCincinnati, OH
Period10/30/0511/4/05

All Science Journal Classification (ASJC) codes

  • Engineering(all)

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