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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    ABSTRACT: The desert gerbil, Psammomys obesus, is a unique polygenic animal model of metabolic syndrome (insulin resistance, obesity and type 2 diabetes), and these pathological conditions resemble to those in human beings. In this study, the animals were fed ad libitum either a natural diet (ND) which contained desertic halophile plants or a standard laboratory diet (STD) or a diet which contained eicosapentaenoic acid (EPA), hence, termed as EPA diet (EPAD). In EPAD, 50% of total lipid content was replaced by EPA oil. By employing real-time PCR, we assessed liver expression of key genes involved in fatty acid metabolism such as PPAR-α, SREBP-1c, LXR-α and CHREBP. We also studied the expression of two inflammatory genes, i.e., TNF-α and IL-1β, in liver and adipose tissue of these animals. The STD, considered to be a high caloric diet for this animal, triggered insulin resistance and high lipid levels, along with high hepatic SREBP-1c, LXR-α and CHREBP mRNA expression. TNF-α and IL-1β mRNA were also high in liver of STD fed animals. Feeding EPAD improved plasma glucose, insulin and triacylglycerol levels along with hepatic lipid composition. These observations suggest that EPA exerts beneficial effects in P. obesus.
    Biochimie 12/2014; 109. DOI:10.1016/j.biochi.2014.12.004 · 2.96 Impact Factor
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    • "The synthesis of other FA-species is then essentially achieved through elongation and desaturation of palmitate. Elongation involves elongases (ELOVL1/3/5/6) while desaturation is achieved by desaturases (SCD1-6, D5D, D6D) [45]. Under the influence of a diet high in carbohydrates (fructose-feeding) DGAT2 is the major enzyme active in the synthesis of TAGs as the storage form of FAs. "
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    ABSTRACT: Fenofibrate (FF) lowers plasma triglycerides via PPARα activation. Here, we analyzed lipidomic changes upon FF treatment of fructose fed rats. Three groups with 6 animals each were defined as control, fructose-fed and fructose-fed/FF treated. Male Wistar Unilever Rats were subjected to 10% fructose-feeding for 20 days. On day 14, fenofibrate treatment (100 mg/kg p.o.) was initiated and maintained for 7 days. Lipid species in serum were analyzed using mass spectrometry (ESI-MS/MS; LC-FT-MS, GC-MS) on days 0, 14 and 20 in all three groups. In addition, lipid levels in liver and intestine were determined. Short-chain TAGs increased in serum and liver upon fructose-feeding, while almost all TAG-species decreased under FF treatment. Long-chain unsaturated DAG-levels (36:1, 36:2, 36:4, 38:3, 38:4, 38:5) increased upon FF treatment in rat liver and decreased in rat serum. FAs, especially short-chain FAs (12:0, 14:0, 16:0) increased during fructose-challenge. VLDL secretion increased upon fructose-feeding and together with FA-levels decreased to control levels during FF treatment. Fructose challenge of de novo fatty acid synthesis through fatty acid synthase (FAS) may enhance the release of FAs ≤16:0 chain length, a process reversed by FF-mediated PPARα-activation.
    PLoS ONE 09/2014; 9(9):e106849. DOI:10.1371/journal.pone.0106849 · 3.23 Impact Factor
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    • "Dietary lipids play a key role in human health and disease and this role is controversial and depends on the type and the amount of ingested fat. Specifically, n-3 long-chain polyunsaturated fatty acids (PUFAs) have been suggested to promote or maintain cardiovascular health [1] [2], mainly due to their antilipidemic [3] [4], anti-inflammatory [5] [6], antiplatelet [7] [8], and antiarrhythmic [9] [10] effects. Unlike the commonly accepted cardio protective role of n-3 PUFAs, other dietary lipids are more controversial. "

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