Open Access Open Access  Restricted Access Subscription Access
Diabetes and Obesity control mechanism

Control of carbohydrate and lipid metabolism by NRF-1 and sirtuins: Implications on type 2 diabetes and obesity

Zane Ferreira, Ademola Ayeleso, Emmanuel Mukwevho

Abstract


The pathogenesis of obesity, insulin resistance and type 2 diabetes can be traced to impaired carbohydrate and lipid metabolism. Carbohydrate and lipid metabolism heavily depend on the mitochondria, which itself is regulated by NRF-1. These metabolic pathways are controlled through the metabolic alterations in concentrations of high energy compounds such as the AMP/ATP and the NAD+/NADH ratios. Decreased concentrations of ATP are able to activate AMPK which in turn activate a versatile transcription factor, NRF-1. The function of NRF-1 is to regulate both carbohydrate and lipid metabolism. On the other hand, changes in the NAD+/NADH ratios affect the activity of other metabolic regulators such as the protein deacetylases called sirtuins. It has been established that sirtuins can increase the activity of the transcriptional coactivator, PGC-1, through deacetylation, the main coactivator of NRF-1. It has however not yet been established whether sirtuins can directly regulate the activity of NRF-1.  This review explores this possibility in relation to carbohydrate and lipid metabolism.

Keywords


Sirtuins; NRF-1; AMPK; Obesity; Type 2 diabetes

Full Text:

PDF

References


A.T. Da Poian, T. El-Bacha, M.R.M.P.Luz. Nutrient Utilization in Humans: Metabolism Pathways. Nature Education. 2010,3,11

B. S. Khakh, G. Burnstock. The double life of ATP. Sci Am. 2009, 301, 84-92

R. Luxton. Clinical Biochemistry(2nd ed), Scion Publishing Ltd: England, 2008.

E. Jéquier. Pathways to obesity. Int. J. Obesity. 2002, 26, S12-S17.

J. Galgani, E. Ravussin. Energy metabolism, fuel selection and body weight regulation. Int J Obes (Lond). 2008, 32(Suppl 7), S109-S119

J. O Hill, H.R. Wyatt, J.C. Peters. Energy Balance and Obesity. Circulation. 2012, 126, 126-132

Carbohydrates in Human Nutrition, Food and Agricultural Organization of the United Nations: Rome,1997.

Z. Yan, V.A. Lira, N.P. Greene. Exercise Training-Induced Regulation of Mitochondrial Quality. Exerc Sport Sci Rev. 2012, 40, 159-164

S.K. Powers, M.J. Jackson. Exercise-Induced Oxidative Stress: Cellular Mechanisms and Impact on Muscle Force Production. Physiol Rev. 2008, 88, 1243-1276

M.K. Campbell, S.O. Farrell. Biochemistry (8th edition). Cengage Learning: USA, 2012

D.J. Voet, J.G. Voet, C.W. Pratt. Principles of Biochemistry(3rd edition), John Wiley & Sons, 2008.

M. Brownlee. The Pathobiology of Diabetic Complications A Unifying Mechanism. Diabetes. 2005,54, 1615-1625.

D.B. Savage, K.F. Petersen, G.I. Shulman. Disordered Lipid Metabolism and the Pathogenesis of Insulin Resistance. Physiol. Rev. 2007, 87, 507-520.

J.D. McGarry. Banting lecture 2001: Dysregulation of Fatty Acid Metabolism in the Etiology of Type 2 Diabetes. Diabetes, 2002,51, 7-18.

M. Quatanani, Lazar, M.A. Mechanisms of obesity-associated insulin resistance: many choices on the menu. Genes & Development, 2007, 21, 1443-1455

R.C. Scarpulla. Transcriptional Paradigms in Mammalian Mitochondrial Biogenesis and Function. Physiol. Rev. 2008, 88,611-638.

F.R. Jornayvaz, G.I. Shulman. Regulation of mitochondrial biogenesis. Essays Biochem. 2010, 47,

Z. Wu, P. Puigeserver, U. Andersson, C. Zhang, G. Adelmant, V. Mootha, A. Troy, S. Cinti, B. Lowell, R.C. Scarpulla, B.M. Spiegelman. Mechanisms Controlling Mitochondrial Biogenesis and Respiration through Thermogenic Coactivator PGC-1. Cell, 1999, 98, 115-124

B. Li,J.O. Holloszy, C.F. Semenkovich. Respiratory uncoupling induces delta-aminolevulinate synthase expression through a nuclear respiratory factor-1-dependant mechanism in HeLa cells. J. Biol. Chem. 1999,274,17534-17540.

B.J. Morris. Seven sirtuins for seven deadly diseases of aging. Free Radic. Biol. Med.2013,56,133-171.

Y. Chen, S. Vaidyanathan. Simultaneous assay of pigments, carbohydrates, proteins and lipids in microalgae. Anal Chim Acta. 2013, 7, 31-40

P.J. Randle. Regulatory Interactions between Lipids and Carbohydrates: The Glucose Fatty Acid Cycle After 35 Years. Diabetes Metab. Rev. 1998, 14, 263-283.

J.M. Berg, J.L. Tymoczko, L., Stryer. Biochemistry (5th ed), W.H. Freeman: New York, 2002.

R. Bergeron, J.M. Ren, K.S. Cadman, I.K. Moore, P. Perret, M. Pypaert, L.H. Young, C.F. Semenkovich, G.I. Shulman. Chronic activation of AMP kinase results in NRF-1 activation and mitochondrial biogenesis. Am. J. Physiol. Endocrinol. Metab. 2001,281, E1340-E1346.

G.L. Russo, M. Russo, P. Ungaro. AMP-activated protein kinase: A target for old drugs against diabetes and cancer. Biochem. Pharmacol. 2013, 86, 339-350.

M.F. Oellirich, M. Potente. FOXOs and Sirtuins in Vascular Growth, Maintenance and Aging. Circ Res. 2012, 110, 1238-1251

L. Tretter, V, Adam-Vizi. Alpha-ketoglutarate dehydrogenase: a target and generator of oxidative stress. Phil. Trans. R. Soc. B. 2005, 360,2335-2345.

P.E. Thorsness, D.E. Koshland. Inactivation of Isocitrate Dehydrogenase by Phosphorylation is Mediated by the Negative Charge of Phosphate. The Journal of Biological Chemistry, 1987, 262, 10422-10425

S. Strumilo. Short-term regulation of the alpha-ketogluterate dehydrogenase complex by energy-linked and some other effectors. Biochem. (Mosc), 2005, 70, 726-729

M.J. Evans, R.C. Scarpulla. NRF-1: a trans-activator of nuclear-encoded respiratory genes in animal cells. Genes Dev.1990, 4, 1023-1034.

S. Gugneja, R.C Scarpulla. Serine Phosphorylation within a Concise Amino-terminal Domain in Nuclear Respiratory Factor 1 Enhances DNA Binding. J. Biol. Chem.1997, 272, 18732-18739.

H. Izumi, R. Ohta, G. Nagatani, T. Ise, Y. Nakayama, M. Nomoto, K. Kohno. p300/CBP-associated factor (P/CAF) interacts with nuclear respiratory factor -1 to regulate the UDP-N¬-acetyl-α-D-galactosamine: polypeptide N-acetylgalactosaminyltransferase-3 gene. Biochem. J. 2003, 373, 713-722.

M.C. Towler, D.G. Hardie. AMP-Activated Protein Kinase in Metabolic Control and Insulin Signalling. Circ. Res. 2007, 100,328-341.

B.B. Kahn. Glucose Transport: Pivotal Step in Insulin Action. Diabetes.1996,45, 1644-1654.

B. Ramachandran, G. Yu, T. Gulick. Nuclear respiratory factor 1 controls myocyte enhancer factor 2A to provide a mechanism for coordinate expression of respiratory chain subunits. J. Biol. Chem.2008,283, 11935-11946.

L.F. Michael, Z. Wu, R.B. Cheatham, P. Puigserver, G. Adelmant, J.J. Lehman, D.P. Kelly, B.M. Spiegelman. Restoration of insulin-sensitive glucose transporter (GLUT4) gene expression in muscle cells by the transcriptional coactivator PGC-1. Proc. Natl. Acad. Sci. USA. 2001, 98, 3820-3825.

C.R. Bruce, A.B. Thrush, V.A. Mettz, V. Bezaire, A. Chabowski, G.J. Heigenhauser, D.J. Dyck. Endurance training in obese humans improves glucose tolerance and mitochondrial fatty acid oxidation and alters muscle lipid content. Am. J. of Physiol. Endocrinol. Metab. 2006, 291,E99-E107.

Y. Xia, L.M. Buja, R.C. Scarpulla, J.B. McMillin. Electrical stimulation of neonatal cardiomyocytes results in the sequential activation of nuclear genes governing mitochondrial proliferation and differentiation. Proc. Natl. Acad. Sci USA. 1997, 94, 11399-11404.

T. Adam, L.H. Opie, M.F. Essop. AMPK activation represses the human gene promoter of the cardiac isoform of acetyl CoA carboxylase: Role of nuclear respiratory factor 1. Biochem.Biophys. Res. Commun. 2010, 398, 495-499.

H. Liang, W.F. Ward. PGC-1α: a key regulator of energy metabolism. Adv. Physiol. Edu. 2006, 30, 145-151.

T. Brun, E. Roche, F. Assimacopoulos-Jeannet, B.E. Corkey, K.-H. Kim, M. Prentki. Evidence for an Anaplerotic/Malonyl-CoA Pathway in Pancreatic β-cell Nutrient Signalling. Diabetes. 1996,45, 190-198.

R. Bressler, S.J. Wakil. Studies on the Mechanism of Fatty Acid Synthesis: IX. The Conversion of Malonyl Coenzyme A to Long Chain Fatty Acids. J. Biol. Chem. 1961, 236, 1643-1651.

K. Morino, K.F. Petersen, S. Dufour, D. Befroy, J. Frattini, N. Shatzkes, S. Neschen, M.F. White, S. Bilz, S. Sono, M. Pypaert, G.I. Shulman. Reduced mitochondrial density and increased IRS-1 serine phosphorylation in muscle of insulin-resistant offspring of type 2 diabetic parents. J. Clin. Invest. 2005, 115, 3587-3593

D.E. Kelley, J. He, E.V., Menshikova, V.B. Ritov. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes. Diabetes.2002, 51, 2944-2950

V.B. Ritov, E.V. Menshikova, J. He, R.E. Ferrell, B.H. Goodpaster, D.E. Kelley. Deficiency of subsarcolemmal mitochondria in obesity and type 2 diabetes. Diabetes. 2005, 54, 8-14

P. Ritz, G. Berrut. Mitochondrial function, energy expenditure, aging and insulin resistance. Diabetes Metab. 2005, 31, 5867-5873

M.E. Patti, A.J. Butte, S. Crunkhorn, K. Cusi, R. Berria, S. Kashyap, Y. Miyazaki, I. Kohane, M. Costello, R. Saccone, E.J. Landaker, A.B. Goldfine, E. Mun, R. DeFronzo, J. Finlayson, C.R. Kahn, L.J. Mandarino. Coordinated reduction of genes of oxidative metabolism in humans with insulin resistance and diabetes: Potential role of PCG1 and NRF1. Proc. Natl. Acad. Sci. USA. 2003,100,8466-8471.

V.K. Mootha, C.M. Lindgren, K.-F. Eriksson, A. Subramanian, S. Sihag, J. Lehar, P. Puigserver, E.Carlsson, M. Ridderstrale, E. Laurila, N. Houstis, M.J. Daly, N. Patterson, J.P. Mesirov, T.R. Golub, P. Tamayo, B. Spiegelman, E.S. Lander, J.N. Hirschhorn, D. Altshuler, L.C. Groop. PGC-1α-responsive genes involved in oxidative phosphorylation are co-ordinately down-regulated in human diabetes. Nat. Gen.2003,34, 267-273.

V.K. Yechoor, M.-E. Patti, R. Saccone, R. Kahn. Coordinated patterns of gene expression for substrate and energy metabolism in skeletal muscle of diabetic mice. Proc. Natl. Acad. Sci USA. 2002, 99, 10587-10592.

X. Wang, X. Wei, Q. Pang, F. Yi. Histone deacetylases and their inhibitors: molecular mechanisms and therapeutic implications in diabetes mellitus. Acta Pharmaceutica Sinica B. 2012, 2,387-395.

R. Karlic, H.-R. Chung, J. Lasserre, K. VlahoviÄek, M. Vingron. Histone modification levels are predictive for gene expression. Proc. Natl. Acad. Sci. USA.2010,107, 2926-2931.

D.M. Taylor, M.M. Maxwell, R. Luthi-Carter, A.G. Kazantsev. Biological and Potential Therapeutic Roles of Sirtuin Deacetylases. Cell. Mol. Life Sci.2008, 65,4000-4018.

C. Canto, Z. Gerhart-Hines, J.N. Feige, M. Lagouge, L. Noriega, J.C. Milne, P.J. Elliott, P. Puigserver, J. Auwerx. AMPK regulates energyexpenditure by modulating NAD+ metabolism and SIRT1 activity. Nature. 2009, 458, 1056-1060.

M. Kitada, D. Koya. SIRT1 in Type 2 Diabetes: Mechanisms and Therapeutic Potential. Diabetes Metab. J.2013,37,315-325.

F. Liang, S. Kume, D. Koya, D. SIRT1 and insulin resistance. Nat. Rev. Endocrinol. 2009,5,367-373.

S.G. Straub, G.W. Sharp. Glucose-stimulated signalling pathways in biphasic insulin secretion. Diabetes Metab. Res. Rev. 2001, 18, 451-463.

A.F. Rowland, D.J. Fazakerley, D.E. James. Mapping Insulin/Glut4 Circuitry. Traffic. 2011,12, 672-681.

T. Kadowaki, T. Yamauchi, N. Kubota, K. Hara, K. Ueki, K. Tobe. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J. Clin. Invest. 2006,116,1784-1792.

Antuna-Puente, B., Feve, B., Fellahi, S., Bastard, J.-P. (2008) Adipokines: The missing link between insulin resistance and obesity. Diabetes & Metabolism, 34, 2-11

Yoshizaki, T., Milne, J.C., Imamura, T., Schenk, S., Sonodoa, N., Babendure, J.L., Lu, J.C., Smith, J.J., Jirousek, M.R., Olefsky, J.M (2009). SIRT1 exerts anti-inflammatory effects and improves insulin sensitivity in adipocytes. Molecular and Cellular Biology, 29, 1363-1374

E. Jing, B. Emanuelli, M.D. Hirschey, J. Boucher, K.Y. Lee, D. Lombard, E.M. Verdin, C.R. Kahn. Sirtuin-3 (SIRT3) regulates skeletal muscle metabolism and insulin signalling via altered mitochondrial oxidation and reactive oxygen species production. Proc. Natl. Acad. Sci. USA. 2011, 108, 14608-14613.

J. Yoshino, S. Imai. Mitochondrial SIRT3: A New Potential Therapeutic Target for Metabolic Syndrome. Mol. Cel., 2011, 44,170-171.

Z. Gerhart-Hines, J.T. Rodgers, O. Bare , C. Lerin,S.-H. Kim, R. Mostoslavsky,F.W. Alt, Z. Wu, P. Puigserver. Metabolic control of muscle mitochondrial function and fatty acid oxidation through SIRT1/PGC-1α. EMBO J. 2007,26,1913-1923.

E.H. Jeninga, K. Schoonjans, J. Auwerx. Reversible acetylation of PGC-1: Connecting energy sensors and effectors to guarantee metabolic flexibility. Oncogene. 2010, 29, 4617-4624.

U. Andersson, R.C. Scarpulla. Pgc-1 regulated coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependant transcription in mammalian cells. Mol. Cell. Biol. 2001,21, 3738-3749.

J.S Joseph, E. Mukwevho. Calmodulin dependant protein kinase (CaMK)-II activation through exercise regulates omega-3 polyunsaturated fatty acids biosynthesis in rat skeletal muscle. Chem. Biol. Lett. 2014, 1, 1-10.






ISSN 2347–9825

Authors/visitors are advised to use Firefox browser for better experience of journal site.

Open Access: Researcher from developing/low economy countries can access the jorunal contents through WHO-HINARI .