Results: 4

1.
Figure 1

Figure 1. From: Fatty Acid-Regulated Transcription Factors in the Liver.

Overview of fatty acid regulation of hepatic gene transcription.

Donald B. Jump, et al. Annu Rev Nutr. 2013;33:249-269.
2.
Figure 2

Figure 2. From: Fatty Acid-Regulated Transcription Factors in the Liver.

Pathways for hepatic fatty acid synthesis (FASN). (a) The pathway describes the conversion of dietary glucose to palmitate by de novo lipogenesis; the pathway requires acetyl CoA carboxylase (ACC)-1 and fatty acid synthase. Palmitate (16:0) is a product of de novo lipogenesis but is also derived from the diet. Palmitate is subsequently elongated [fatty acid elongase (Elov)l5 and Elovl6] and desaturated [stearoyl CoA desaturase (SCD)] to form C16–18 saturated and monounsaturated (ω7 and ω9) fatty acids. (b) The essential fatty acids, linoleic acid (18:2, ω6) and α-linolenic acid (18:3, ω3), are derived from the diet. These fatty acids are desaturated [fatty acid desaturases (FADS)1 and FADS2] and elongated (Elovl2 and Elovl5) to form the major C20–22 polyunsaturated fatty acids (PUFAs) appearing in cells, i.e., arachidonic acid (ARA; 20:4, ω6) and docosahexaenoic acid (DHA; 22:6, ω3). DHA production requires peroxisomal β-oxidation (p-βOx). C22 PUFAs are retroconverted to C20 PUFAs by p-βOx.

Donald B. Jump, et al. Annu Rev Nutr. 2013;33:249-269.
3.
Figure 3

Figure 3. From: Fatty Acid-Regulated Transcription Factors in the Liver.

Nutrient and hormonal regulation of sterol regulatory element–binding protein-1c (SREBP-1c) nuclear abundance. The diagram illustrates the levels of control of SREBP-1c, from gene transcription to degradation of the protein. See text for details on sites of control and regulation of SREBP-1c nuclear abundance. Insulin and liver X receptor (LXR) agonist induce (+) SREBP-1c nuclear abundance, whereas unsaturated fatty acids (UFAs), docosahexaenoic acid (DHA), and cholesterol lower (−) SREBP-1c nuclear abundance. Several enzymes are involved in covalently modifying nuclear SREBP-1, including protein kinase A (PKA), glycogen synthase kinase-3β, extracellular receptor kinase-1 or -2 (Erk1/2), or ubiquitin ligase (SCFFbw7). Several proteins are also involved in controlling SREBP processing, including insulin-inducible gene (Insig-1 or Insig-2), SREBP coactivating protein (SCAP), site-1 protease (S1P), and site-2 protease (S2P). Abbreviations: GSK-3β, glycogen synthase kinase-3β; mTORC, mammalian target of rapamycin complex; Ubxd8, ubiquitin regulatory X d8; +, induction; -, repression or inhibition; ?, mechanism not defined.

Donald B. Jump, et al. Annu Rev Nutr. 2013;33:249-269.
4.
Figure 4

Figure 4. From: Fatty Acid-Regulated Transcription Factors in the Liver.

The role of endogenous fatty acid metabolism in the control of hepatic gene transcription. The generation of fatty acids within hepatic parenchymal cells affects the control of at least three transcription factors, peroxisome proliferator-activated receptor α(PPARα), sterol regulatory element–binding protein 1 (SREBP-1), and forkhead box O1 (FoxO1). The mechanisms include the production of fatty acids by de novo lipogenesis (DNL) and monounsaturated fatty acid (MUFA) (18:1, ω7) and polyunsaturated fatty acid (PUFA) (C20–22 ω3 and ω6 PUFA) synthesis. SREBP-1 nuclear abundance is well suppressed by C20–22 PUFA, and hepatic conversion of essential fatty acids to C20–22 PUFA suppresses SREBP-1 nuclear abundance and DNL. Because this pathway produces both C20 and C22 PUFAs, PPARα signaling can be affected. C20 PUFAs, but not C22 PUFAs, are robust activators of PPARα. FoxO1 activity is not affected by exogenous fatty acids or endogenous production of PUFAs. FoxO1 nuclear abundance, however, is regulated by mechanisms that control hepatic conversion of palmitoleic acid (16:1, ω7) to cis-vaccenic acid (18:1, ω7). Increased hepatic production of 18:1, ω7 induces production of rictor, a component of mTORC2. mTORC2 phosphorylates Akt-S473, and active Akt phosphorylates FoxO1-S256. Phospho-FoxO1 is excluded from nuclei and degraded in the proteasome. The outcome is suppressed expression of genes involved in gluconeogenesis (GNG) and hepatic glucose production (HGP). The up ( green) and down (red ) block arrows represent induction or repression of the pathway or transcription factor. Abbreviations: CTE1, cytosolic thioesterase-1; CYP4A, cytochrome P450-4A; Elovl, fatty acid elongase; G6Pase, glucose-6 phosphatase; mRNA, messenger ribonucleic acid; Pck1, phosphoenolpyruvate carboxykinase.

Donald B. Jump, et al. Annu Rev Nutr. 2013;33:249-269.

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