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Polyunsaturated fatty acid regulation of gene transcription: a mechanism to improve energy balance and insulin resistance

Published online by Cambridge University Press:  09 March 2007

Steven D. Clarke
Steven D. Clarke*
Affiliation:
Graduate Program of Nutritional Sciences, The University of Texas at Austin, 115 Gearing Building, Austin, Texas, 78712, USA
*
Corresponding author: S. D. Clarke, fax +1 512 471 5630, email [email protected]
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Abstract

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This review addresses the hypothesis that polyunsaturated fatty acids (PUFA), particularly those of the n-3 family, play essential roles in the maintenance of energy balance and glucose metabolism. The data discussed indicate that dietary PUFA function as fuel partitioners in that they direct glucose toward glycogen storage, and direct fatty acids away from triglyceride synthesis and assimilation and toward fatty acid oxidation. In addition, the n-3 family of PUFA appear to have the unique ability to enhance thermogenesis and thereby reduce the efficiency of body fat deposition. PUFA exert their effects on lipid metabolism and thermogenesis by up-regulating the transcription of the mitochondrial uncoupling protein-3, and inducing genes encoding proteins involved in fatty acid oxidation (e.g. carnitine palmitoyltransferase and acyl-CoA oxidase) while simultaneously down-regulating the transcription of genes encoding proteins involved in lipid synthesis (e.g. fatty acid synthase). The potential transcriptional mechanism and the transcription factors affected by PUFA are discussed. Moreover, the data are interpreted in the context of the role that PUFA may play as dietary factors in the development of obesity and insulin resistance. Collectively the results of these studies suggest that the metabolic functions governed by PUFA should be considered as part of the criteria utilized in defining the dietary needs for n-6 and n-3 PUFA, and in establishing the optimum dietary ratio for n-6 : n-3 fatty acids.

Keywords

Polyunsaturated fatty acidsGene transcriptionInsulin resistance
Type
Research Article
Information
British Journal of Nutrition , Volume 83 , Issue S1 , June 2000 , pp. S59 - S66
Copyright
Copyright © The Nutrition Society 2000

References

Allmann, DW & Gibson, DW (1969) Fatty acid synthesis during early linoleic acid deficiency in the mouse. Journal of Lipid Research 6, 51–62.CrossRefGoogle Scholar
Anderson, JW, Herman, RH & Zakim, D (1973) Effect of high glucose and high sucrose diets on glucose tolerance of normal men. American Journal of Clinical Nutrition 26, 600–606.CrossRefGoogle ScholarPubMed
Baillie, RA, Takada, R, Nakamura, M & Clarke, SD (1999) Coordinate induction of peroxisomal acyl-CoA oxidase and UCP-3 by dietary fish oil: a mechanism for decreased body fat deposition. Prostaglandins, Leukotrienes and Essential Fatty Acids 60, 351–356.Google Scholar
Baur, LA, O'Connor, J, Pan, DA, Kritketos, A & Storlien, LH (1998) The fatty acid composition of skeletal muscle membrane phospholipid: its relationship with the type of feeding and plasma glucose levels in young children. Diabetes 47, 106–112.Google ScholarPubMed
Boden, G & Chen, XH (1995) Effects of fat on glucose uptake and utilization in patients with non-insulin-dependent diabetes. Journal of Clinical Investigation 96, 1261–1268.Google Scholar
Boss, O, Muzzin, P. & Giacobino, JP (1998) The uncoupling proteins, a review. European Journal of Endocrinology 139, 1–9.Google Scholar
Brown, MS & Goldstein, JL (1999) A proteolytic pathway that controls the cholesterol content of membranes, cells, and blood. Proceedings of the National Academy of Sciences, USA 96, 1041–11048.Google Scholar
Brun, RP, Kim, JB, Hu, E, Altiok, S & Spiegelman, BM (1996) Adipocyte differentiation: a transcriptional regulatory cascade. Current Opinion in Cell Biology 8, 826–832.CrossRefGoogle ScholarPubMed
Cho, HP, Nakamura, MT & Clarke, SD (1999) Cloning, expression, and nutritional regulation of the mammalian Δ-6 desaturase. Journal of Biological Chemistry 274, 471–477.CrossRefGoogle ScholarPubMed
Clarke, SD (1999) Polyunsaturated fatty acids as fuel partitioners: a transcriptional mechanism. Chemistry and Physics of Lipids 101, 141.Google Scholar
Clarke, SD & & Jump, DB (1993) Regulation of hepatic gene expression by dietary fats: a unique role for polyunsaturated fatty acids. In Nutrition and Gene Expression, pp. 227–245 [Berdanier, CD & Hargrove, JL, editors]. Boca Raton, FL: CRC Press.Google Scholar
Clarke, SD, Armstrong, MK & Jump, DB (1990) Dietary polyunsaturated fats uniquely suppress rat liver fatty acid synthase and S14 mRNA content. Journal of Nutrition 120, 225–232.CrossRefGoogle ScholarPubMed
Clarke, SD, Baillie, R, Jump, DB & Nakamura, MT (1997) Fatty acid regulation of gene expression: its role in fuel partitioning and insulin resistance. Annals of the New York Academy of Sciences 827, 178–187.CrossRefGoogle ScholarPubMed
Clarke, SD, Thuillier, P, Baillie, RA & Sha, X (1999) Peroxisome proliferator-activated receptors: a family of lipid-activated transcription factors. American Journal of Clinical Nutrition 70, 566–577.CrossRefGoogle ScholarPubMed
Costet, P, Legendre, C, More, J, Edgar, A, Galtier, P & Pineau, T (1998) Peroxisome proliferator-activated receptor a-isoform deficiency leads to progressive dyslipidemia with sexually dimorphic obesity and steatosis. Journal of Biological Chemistry 273, 29577–29585.CrossRefGoogle Scholar
Couet, C, Delarue, J, Fitz, P, Antonine, JM & Lamisse, F (1997) Effect of dietary fish oil on body fat mass and basal fat oxidation in healthy adults. International Journal of Obesity 21, 637–643.Google Scholar
Da Silva, AL, De Marcucci, OL & Kuhnle, ZR (1993) Dietary polyunsaturated fats suppress the high-sucrose induced increase of rat liver pyruvate dehydrogenase levels. Biochimica Biophysica Acta 1169, 126–134.Google Scholar
DuBois, RN, Gupta, R, Brockman, J, Reddy, BS, Krakow, SL & Lazar, MA (1998) The nuclear eicosanoid receptor, PPARγ, is aberrantly expressed in colonic cancers. Carcinogenesis 19, 49–53.CrossRefGoogle ScholarPubMed
Field, CJ, Ryan, EA, Thomson, ABR & Clandinin, MT (1990) Diet fat composition alters membrane phospholipid composition, insulin binding and glucose metabolism in adipocytes from control and diabetic animals. Journal of Biological Chemistry 265, 11143–11150.Google Scholar
Fleury, C, Neverova, M, Collins, S, Raimbault, S, Champigny, O, Levi-Meyrueis, C, Bouillaud, F, Seldin, MF, Surwit, RS, Ricquirer, D & Warden, CH (1997) Uncoupling protein-2: a novel gene linked to obesity and hyperinsulinemia. Nature Genetics 15, 269–272.Google Scholar
Foellmi-Adams, LA, Wyse, BM, Herron, D, Nedergarrd, J & Kletzien, RF (1996) Induction of uncoupling protein in brown adipose tissue. Synergy between norepinephrine and pioglitazone, an insulin-sensitizing agent. Biochemical Pharmacology 52, 693–701.Google Scholar
Kliewer, SA, Sundseth, SS, Jones, SA, Brown, PJ, Wisely, GB, Koble, CS, Devachand, P, Wahli, W, Willson, TM, Lenhard, J & Lehmann, JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors α and γ. Proceedings of the National Academy of Sciences, USA 94, 4318–4323.CrossRefGoogle ScholarPubMed
Forman, BM, Tontonoz, P, Chen, J, Brun, RP, Spiegelman, BM & Evans, RM (1995) 15-deoxy-D-12,14-prostaglandin J2 is a ligand for the adipocyte determination factor PPARγ. Cell 83, 803–812.CrossRefGoogle Scholar
Gasperikova, D, Klimes, I, Kolter, T, Bohov, P, Maassen, A, Eckel, J, Clandinin, MT & Sebova, E (1997) Glucose transport and insulin signaling in rat muscle and adipose tissue: effect of lipid availability. Proceedings of the New York Academy of Sciences 827, 144–157.Google Scholar
Hertz, R, Magenheim, J, Berman, I, Bar-Tana, J (1998) Fatty acid-CoA esters are ligands of hepatic nuclear factor-4α. Nature 392, 512–516.Google Scholar
Hill, JO, Peters, JC, Lin, D, Yakubu, F, Greene, H & Swife, L (1993) Lipid accumulation and body fat distribution is influenced by type of dietary fat fed to rats. International Journal of Obesity 17, 223–236.Google ScholarPubMed
Issemann, I & Green, S (1990) Activation of a member of the steroid hormone receptor superfamily by peroxisome proliferators. Nature 347, 645–650.CrossRefGoogle ScholarPubMed
Jaburek, M, Varecha, M, Gimeno, RE, Dembski, M, Jezek, P, Zhang, M, Burn, P, Tartaglia, LA & Garlid, KD (1999) Transport function and regulation of mitochondrial uncoupling proteins 2 and 3. Journal of Biological Chemistry 274, 26003–26007.Google Scholar
Jump, DB & Clarke, SD (1999) Regulation of gene expression by dietary fat. Annual Review of Nutrition 19, 63–90.CrossRefGoogle ScholarPubMed
Jump, D, Clarke, SD, Thelen, A & Liimatta, M (1994) Coordinate regulation of glycolytic and lipogenic gene expression by polyunsaturated fatty acids. Journal of Lipid Research 35, 1076–1084.CrossRefGoogle ScholarPubMed
Kahn, B & Pedersen, O (1993) Suppression of GLUT 4 expression skeletal muscle of rats that are obese from high fat feeding but not from high carbohydrate feeding or genetic obesity. Endocrinology 132, 13–22.Google Scholar
Kahn, SH & Sorof, S (1994) Liver fatty acid-binding protein: specific mediator of the mitogenesis induced by two classes of carcinogenic peroxisome proliferators. Proceedings of the National Academy of Sciences, USA 91, 848–852.CrossRefGoogle Scholar
Katsurada, A, Iritani, N, Fukuda, H, Noguchi, T & Tanaka, T (1990) Influence of nutrients and hormones on transcriptional and post-transcriptional regulation of acetyl-CoA carboxylase in rat liver. European Journal of Biochemistry 190, 435–441.Google Scholar
Kawashima, Y, Musoh, K & Kozuka, H (1990) Peroxisome proliferators enhance linoleic acid metabolism in rat liver. Journal of Biological Chemistry 265, 9170–9175.CrossRefGoogle ScholarPubMed
Kletzien, RF, Foellmi, LA, Harris, PKW, Wyse, BM & Clarke, SD (1992) Adipocyte fatty acids binding protein (aFABP): regulation of gene expression in vivo and in vitro by an insulin-sensitizing agent. Molecular Pharmacology 42, 558–562.Google Scholar
Kliewer, SA, Sundseth, SS, Jones, SA, Brown, PJ, Wisely, GB, Koble, CS, Devachand, P, Wahli, W, Willson, TM, Lenhard, J & Lehmann, JM (1997) Fatty acids and eicosanoids regulate gene expression through direct interactions with peroxisome proliferator-activated receptors. Proceedings of the National Academy of Sciences, USA 94, 4318–4323.CrossRefGoogle ScholarPubMed
Kolterman, OG, Greenfield, GM, Reaven, GM, Saekow, M & Olefsky, JM (1979) Effect of a high carbohydrate diet on insulin binding to adipocytes and on insulin action in vivo in man. Diabetes 28, 731–736.CrossRefGoogle ScholarPubMed
Kondrup, J & Lazarow, PB (1985) Flux of palmitate through the peroxisomal and mitochondrial beta-oxidation systems in isolated rat hepatocytes. Biochimica Biophysica Acta 835, 147–153.Google Scholar
Liimatta, M, Towle, HC, Clarke, SD & Jump, DB (1994) Dietary polyunsaturated fatty acids interfere with the insulin/glucose activation of L–type pyruvate kinase gene transcription. Molecular Endocrinology 8, 1147–1153.Google ScholarPubMed
Malasanos, TH & Stacpoole, PW (1991) Biological effects of n-3 fatty acids in diabetes mellitus. Diabetes Care 14, 1160–1179.CrossRefGoogle ScholarPubMed
Martin, G, Schoonjans, K, Lefebvre, AM, Staels, B & Auwerx, J (1997) Coordinate regulation of the expression of the fatty acid transport protein and acyl-CoA synthetase genes by PPARα and PPARγ activators. Journal of Biological Chemistry 272, 28210–28217.CrossRefGoogle ScholarPubMed
Mascaro, C, Acosta, E, Ortiz, JA, Marrero, PF, Hegardt, FG & Haro, D (1998) Control of human muscle-type carnitine palmitoyltransferase I gene transcription by peroxisome proliferator-activated receptor. Journal of Biological Chemistry 273, 8560–8563.CrossRefGoogle ScholarPubMed
Mater, MK, Pan, D, Bergen, WG & Jump, DB (1998) Arachidonic acid inhibits lipogenic gene expression in 3T3-L adipocytes through a prostanoid pathway. Journal of Lipid Research 39, 1327–1334.Google Scholar
Matsui, H, Okumura, K, Kawakami, K, Hibino, M, Toki, Y & Ito, T (1997) Improved insulin sensitivity by bezafibrate in rats. Relationship to fatty acid composition of skeletal muscle triglycerides. Diabetes 46, 348–353.Google Scholar
Nestel, PJ, Connor, WE, Reardon, MF, Connors, S, Wong, S, Boston, R. (1984) Suppression by diets rich in fish oil of very low density lipoprotein production in man. Journal of Clinical Investigation 74, 82–89.CrossRefGoogle Scholar
Nolan, JJ, Ludvik, B, Beerdsen, P, Joyce, M & Olefsky, J (1994) Improvement in glucose tolerance and insulin resistance in obese subjects treated with troglitazone. New England Journal of Medicine 331, 1188–1193.CrossRefGoogle ScholarPubMed
Olefsky, JM & Saekow, M (1978) The effects of dietary carbohydrate content on insulin binding and glucose metabolism by isolated rat adipocytes. Endocrinology 103, 2252–2263.CrossRefGoogle ScholarPubMed
Podolin, DA, Gayles, EC, Wei, Y, Thresher, JS & Pagliassotti, MJ (1998) Menhaden oil prevents but does not reverse sucrose-induced insulin resistance in rats. Proceedings of the National Academy of Sciences, USA 96, 11041–11048.Google Scholar
Power, GW & Newsholme, EA (1997) Dietary fatty acids influence the activity and metabolic control of mitochondrial carnitine palmitoyltransferase I in rat heart and skeletal muscle. Journal of Nutrition 127, 2142–2150.Google Scholar
Prentki, M & Corkey, BE (1996) Are the β-cell signaling molecules malonyl-CoA and cytosolic long-chain acyl-CoA implicated in multiple tissue defects of obesity and NIDDM?. Diabetes 45, 273–283.CrossRefGoogle ScholarPubMed
Reddy, JK & Mannaerts, GP (1994) Peroxisomal lipid metabolism. Annual Review of Nutrition 14, 343–370.CrossRefGoogle ScholarPubMed
Rodriguez, JC, Gil-Gomez, B, Hegradt, FG & Haro, D (1994) Peroxisome proliferator-activated receptor mediates induction of the mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase gene by fatty acids. Journal of Biological Chemistry 269, 1867–1872.Google Scholar
Saha, AK, Kurowski, TG & Ruderman, NB (1995) A malonyl-CoA fuel sensing mechanism in muscle: effects of insulin glucose, and denervation. American Journal of Physiology 269, E383-E289.Google ScholarPubMed
Saloranta, C, Koivisto, V, Widen, E, Falholt, K, DeFronzo, RA, Harkonen, M & Groop, L (1993) Contribution of muscle and liver to glucose–fatty acid cycle in humans. American Journal of Physiology 264, E599-E605.Google Scholar
Schrauwen, P, Walder, K & Ravussin, E (1999) Human uncoupling proteins and obesity. Obesity Research 7, 97–105.Google Scholar
Shimomura, I, Shimano, H, Korn, BS, Bashmakov, Y & Horton, JD (1998) Nuclear sterol regulatory element-binding proteins activate genes responsible for the entire program of unsaturated fatty acid biosynthesis in transgenic mouse liver. Journal of Biological Chemistry 273, 35299–35306.CrossRefGoogle ScholarPubMed
Solanes, G, Vidal-Puig, A, Grujic, D, Flier, JS & Lowell, BB (1997) The human uncoupling protein-3 gene. Journal of Biological Chemistry 272, 25433–25436.CrossRefGoogle ScholarPubMed
Staels, B, Schoonjans, K, Fruchart, JC & Auwerx, J (1998) The effects of fibrates and thiazolidinediones on plasma triglyceride metabolism are mediated by distinct peroxisome proliferator activated receptors (PPARs). Biochimie 79, 95–99.CrossRefGoogle Scholar
Storlien, LH, Kraegen, WE, Chisholm, DJ, Ford, GL, Bruce, DG & Pascoe, WE (1987) Fish oil prevents insulin resistance induced by high fat feeding in rats. Science 237, 885–888.Google Scholar
Storlien, LH, Jenkins, AB, Chisholm, DJ, Pascoe, WS, Khouri, S & Kraegen, EW (1991) Influence of dietary fat composition on development of insulin resistance: relationship to muscle triglyceride and n-3 fatty acids in muscle phospholipids. Diabetes 40, 280–289.Google Scholar
Takada, R, Saitoh, M & Mori, T (1994) Dietary gamma-linolenic acid enriched oil reduces body fat content and induces liver enzyme activities relating to fatty acid beta-oxidation in rats. Journal of Nutrition 124, 469–479.CrossRefGoogle ScholarPubMed
Thomassen, MS, Christiansen, EN & Norum, KR (1982) Characterization of the stimulatory effect of high fat diets on peroxisomal β-oxidation in rat liver. Biochemical Journal 206, 195–202.CrossRefGoogle ScholarPubMed
Tontonoz, P, Nagy, L, Alvarez, JGA, Thomazy, VA & Evans, RM (1998) PPARγ promotes monocyte/macrophage differentiation and uptake of oxidized LDL. Cell 93, 241–252.Google Scholar
Van Epps-Fung, M, Williford, J, Wells, A & Hardy, RW (1997) Fatty acid induced insulin resistance in adipocytes. Endocrinology 138, 4338–4345.CrossRefGoogle ScholarPubMed
Varanasi, U, Chu, R, Huang, Q, Castellon, R, Yeldani, AV & Reddy, JK (1996) Identification of a peroxisome proliferator-responsive element upstream of the human peroxisomal fatty acyl coenzyme A oxidase gene. Journal of Biological Chemistry 271, 2147–2155.CrossRefGoogle ScholarPubMed
Vidal-Puig, A, Solanes, G, Grujic, D, Flier, FS & Lowell, BB (1997) UCP3: an uncoupling protein homologue expressed preferentially and abundantly in skeletal muscle and brown adipose tissue. Biochemical and Biophysical Research Communications 235, 79–82.CrossRefGoogle ScholarPubMed
Weigle, DS, Sefridge, LE, Schwartz, MW, Seeley, RJ, Cummings, DE, Havel, PJ, Kuijper, JL & Beltrandel-Rio, H (1999) Elevated free fatty acids induce uncoupling protein 3 expression in muscle. Diabetes 47, 298–302.CrossRefGoogle Scholar
Wilson, MD, Salati, LM, Blake, WL & Clarke, SD (1990) The potency of polyunsaturated and saturated fats as short term inhibitors of hepatic lipogenesis. Journal of Nutrition 120, 544–552.CrossRefGoogle ScholarPubMed
Wong, SH, Nestel, PJ, Trimble, RP, Storere, GB, Illman, RJ, Topping, DL. (1984) The adaptive effects of dietary fish and safflower oil on lipid and lipoprotein metabolism in perfused rat liver. Biochimica Biophysica Acta 792, 103–109.CrossRefGoogle ScholarPubMed
Worgall, TS, Sturley, SL, Seo, T, Osborne, TF & Deckelman, RJ (1998) Polyunsaturated fatty acids decrease expression of promoters with sterol regulatory elements by decreasing levels of mature sterol regulatory element binding protein. Journal of Biological Chemistry 273, 25537–25540.Google Scholar
Xu, J, Nakamura, T, Cho, HP & Clarke, SD (1999) Sterol regulatory element binding protein-1 expression is suppressed by dietary polyunsaturated fatty acids. Journal of Biological Chemistry 274, 23577–23588.CrossRefGoogle ScholarPubMed
Zierath, JR, Houseknecht, KL, Gnudi, L & Kahn, BB (1997) High-fat feeding impairs insulin-stimulated GLUT4 recruitment via an early insulin signaling defect. Diabetes 46, 215–223.CrossRefGoogle ScholarPubMed