Fatty acid regulation of hepatic lipid metabolism

Department of Nutrition and Exercise Sciences, The Linus Pauling Institute, Oregon State University, Corvallis, Oregon 97331, USA.
Current opinion in clinical nutrition and metabolic care 03/2011; 14(2):115-20. DOI: 10.1097/MCO.0b013e328342991c
Source: PubMed


To discuss transcriptional mechanisms regulating hepatic lipid metabolism.
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.
These studies may help define novel strategies to control fatty liver and hyperglycemia associated with NIDDM and MetS.

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Available from: Donald Jump, Nov 19, 2015
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    • "Moreover, several reports have shown beneficial effects of fish oils, containing n-3 polyunsaturated fatty acids (PUFAs) such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), in T2D in rodents and human beings [6]. The n-3 PUFAs exert protective effects , in part, by controlling synthesis and oxidation of saturated and monounsaturated fatty acids, thus, lowering hepatic fat contents and improving blood lipid profiles [7]. Besides, due to their anti-inflammatory properties, n-3 PUFAs could influence hepatic metabolism in context of insulin resistance and obesity. "
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    • "The scheme is not in scale and modified from (Sato et al., 1994). indirect effects of SREBP-1c phosphorylation, as differences of lipid accumulation or lipid composition in the cells might be sufficient to alter the respective secretome of the cells (Jump, 2011). Many of the secreted proteins observed in our study have a known impact on liver metabolism, growth or regeneration, like the Apo proteins, alpha-1-antitrypsin, annexin 4 or IGFBP-1. "
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