TitleFatty acid regulation of hepatic lipid metabolism.
Publication TypeJournal Article
Year of Publication2011
AuthorsJump DB
JournalCurr Opin Clin Nutr Metab Care
Volume14
Issue2
Pagination115-20
Date Published2011 Mar
ISSN1473-6519
KeywordsDiabetes Mellitus, Type 2, Dietary Fats, Disease Progression, Fatty Acids, Unsaturated, Fatty Liver, Humans, Lipid Metabolism, Liver, Metabolic Syndrome
Abstract

PURPOSE OF REVIEW: To discuss transcriptional mechanisms regulating hepatic lipid metabolism.

RECENT FINDINGS: Humans who are obese or have diabetes (NIDDM) or metabolic syndrome (MetS) have low blood and tissue levels of C20-22 polyunsaturated fatty acids (PUFAs). Although the impact of low C20-22 PUFAs on disease progression in humans is not fully understood, studies with mice have provided clues suggesting that impaired PUFA metabolism may contribute to the severity of risk factors associated with NIDDM and MetS. High fat diets promote hyperglycemia, insulin resistance and fatty liver in C57BL/6J mice, an effect that correlates with suppressed expression of enzymes involved in PUFA synthesis and decreased hepatic C20-22 PUFA content. A/J mice, in contrast, are resistant to diet-induced obesity and diabetes; these mice have elevated expression of hepatic enzymes involved in PUFA synthesis and C20-22 PUFA content. Moreover, loss-of-function and gain-of-function studies have identified fatty acid elongase (Elovl5), a key enzyme involved in PUFA synthesis, as a regulator of hepatic lipid and carbohydrate metabolism. Elovl5 activity regulates hepatic C20-22 PUFA content, signaling pathways (Akt and PP2A) and transcription factors (SREBP-1, PPARα, FoxO1 and PGC1α) that control fatty acid synthesis and gluconeogenesis.

SUMMARY: These studies may help define novel strategies to control fatty liver and hyperglycemia associated with NIDDM and MetS.

DOI10.1097/MCO.0b013e328342991c
Alternate JournalCurr Opin Clin Nutr Metab Care
PubMed ID21178610
PubMed Central IDPMC3356999
Grant ListR01 DK043220 / DK / NIDDK NIH HHS / United States
DK43220 / DK / NIDDK NIH HHS / United States