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Role of ACOT1 in hepatic lipid trafficking (821.6)
Author(s) -
Franklin Mallory,
Sathyanarayan Aishwarya,
Mashek Mara,
Mashek Douglas
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.821.6
Subject(s) - lipid metabolism , peroxisome , gene knockdown , triglyceride , regulator , endocrinology , medicine , peroxisome proliferator activated receptor , transcription factor , metabolism , lipid droplet , biology , lipid metabolism disorder , chemistry , biochemistry , cholesterol , blood lipids , receptor , gene
Peroxisome proliferator‐activated regulator alpha (PPARα) is a major regulator of fasting lipid metabolism. PPARα induces transcription of cytosolic Acyl‐CoA Thioesterase 1 (ACOT1), which hydrolyzes acyl‐CoAs into long‐chain free fatty acids and Coenzyme A. However, the physiological role of ACOT1 in lipid metabolism is not known. Thus, the objective of this research was to determine the contribution of hepatic ACOT1 to lipid metabolism and signaling. To test our objectives, we injected C57/Bl6 mice with an adenovirus harboring shRNA targeted to ACOT1 or a scrambled control. One week post‐injection, mice were fasted overnight and sacrificed. Compared to control mice, ACOT1 knockdown resulted in an increase in serum β‐hydroxybutyrate, a marker of fatty acid oxidation, and an increase in serum triglyceride, indicating a possible increase in very‐low density lipoprotein secretion. These changes were not accompanied by a significant change in liver triglyceride. In addition, genes involved in mitochondrial biogenesis were decreased in response to ACOT1 knockdown suggesting that ACOT1 alters cell signaling to influence gene expression. In summary, these results show that ACOT1 plays an important role in regulating hepatic lipid metabolism and may serve an important novel role in trafficking of lipids to influence cell signaling.