Sirtuin 1 in lipid metabolism and obesity

Abstract Sirtuin 1 (SIRT1), the mammalian ortholog of yeast Sir2, is a highly conserved NAD+-dependent protein deacetylase that has emerged as a key metabolic sensor that directly links environmental nutrient signals to animal metabolic homeostasis. SIRT1 is known to be involved in gluconeogenesis in the liver, fat mobilization in white adipose tissue, and insulin secretion in the pancreas. Recent studies have shown SIRT1 to regulate fatty acid oxidation in the liver, sense nutrient availability in the hypothalamus, influence obesity-induced inflammation in macrophages, and modulate the activity of the circadian clock in metabolic tissues. The activity of SIRT1 also appears to be under the control of AMPK and adiponectin. This review focuses on the involvement of SIRT1 in regulating metabolic diseases associated with obesity. It includes brief overviews of sirtuin signaling, with emphasis on SIRT1's role in the liver, macrophage, brain, and adipose tissue as it relates to obesity.

[1]  M. Pallàs,et al.  Sirtuin activators: designing molecules to extend life span. , 2010, Biochimica et biophysica acta.

[2]  A. Cuervo,et al.  Autophagic pathways and metabolic stress , 2010, Diabetes, obesity & metabolism.

[3]  T. Veenstra,et al.  SIRT1 Deacetylates and Inhibits SREBP-1C Activity in Regulation of Hepatic Lipid Metabolism* , 2010, The Journal of Biological Chemistry.

[4]  M. Dietrich,et al.  Agrp Neurons Mediate Sirt1's Action on the Melanocortin System and Energy Balance: Roles for Sirt1 in Neuronal Firing and Synaptic Plasticity , 2010, The Journal of Neuroscience.

[5]  A. Cuervo,et al.  Autophagy and lipids: tightening the knot , 2010, Seminars in Immunopathology.

[6]  I. Rahman,et al.  Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism: implication in pathogenesis of COPD. , 2010, Archives of biochemistry and biophysics.

[7]  M. Haigis,et al.  Sirtuins regulate key aspects of lipid metabolism. , 2010, Biochimica et biophysica acta.

[8]  P. Puigserver,et al.  Nutrient-dependent regulation of PGC-1alpha's acetylation state and metabolic function through the enzymatic activities of Sirt1/GCN5. , 2010, Biochimica et biophysica acta.

[9]  M. Goligorsky.  SIRTing out the link between autophagy and ageing. , 2010, Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association.

[10]  D. Holtzman,et al.  SIRT1 Promotes the Central Adaptive Response to Diet Restriction through Activation of the Dorsomedial and Lateral Nuclei of the Hypothalamus , 2010, The Journal of Neuroscience.

[11]  W. Johnson,et al.  Prediabetes and prehypertension in disease free obese adults correlate with an exacerbated systemic proinflammatory milieu , 2010, Journal of Inflammation.

[12]  Qing Xu,et al.  Myeloid Deletion of SIRT1 Induces Inflammatory Signaling in Response to Environmental Stress , 2010, Molecular and Cellular Biology.

[13]  R. Coppari,et al.  SIRT1 deacetylase in POMC neurons is required for homeostatic defenses against diet-induced obesity. , 2010, Cell metabolism.

[14]  P. Puigserver,et al.  Conserved role of SIRT1 orthologs in fasting-dependent inhibition of the lipid/cholesterol regulator SREBP. , 2010, Genes & development.

[15]  T. Suganami,et al.  Adipose tissue macrophages: their role in adipose tissue remodeling , 2010, Journal of leukocyte biology.

[16]  F. Gao,et al.  Engineering hybrid nanotube wires for high-power biofuel cells. , 2010, Nature communications.

[17]  F. Mulero,et al.  Sirt1 improves healthy ageing and protects from metabolic syndrome-associated cancer. , 2010, Nature communications.

[18]  Y. Hayashi,et al.  Adiponectin and AdipoR1 regulate PGC-1α and mitochondria by Ca2+ and AMPK/SIRT1 , 2010, Nature.

[19]  J. Auwerx,et al.  Interdependence of AMPK and SIRT1 for metabolic adaptation to fasting and exercise in skeletal muscle. , 2010, Cell metabolism.

[20]  J. Olefsky,et al.  SIRT1 inhibits inflammatory pathways in macrophages and modulates insulin sensitivity. , 2010, American journal of physiology. Endocrinology and metabolism.

[21]  T. Schug,et al.  DYRK1A and DYRK3 Promote Cell Survival through Phosphorylation and Activation of SIRT1* , 2010, The Journal of Biological Chemistry.

[22]  T. Hirota,et al.  DYRK1A and Glycogen Synthase Kinase 3β, a Dual-Kinase Mechanism Directing Proteasomal Degradation of CRY2 for Circadian Timekeeping , 2010, Molecular and Cellular Biology.

[23]  D. Fairlie,et al.  Inflammatory lipid mediators in adipocyte function and obesity , 2010, Nature Reviews Endocrinology.

[24]  G. Gores,et al.  Deleted in breast cancer-1 regulates SIRT1 activity and contributes to high-fat diet-induced liver steatosis in mice. , 2010, The Journal of clinical investigation.

[25]  Venkataraman Thanabal,et al.  SRT1720, SRT2183, SRT1460, and Resveratrol Are Not Direct Activators of SIRT1♦ , 2010, The Journal of Biological Chemistry.

[26]  R. de Cabo,et al.  JNK1 Phosphorylates SIRT1 and Promotes Its Enzymatic Activity , 2009, PloS one.

[27]  L. Guarente,et al.  Neuronal SIRT1 regulates endocrine and behavioral responses to calorie restriction. , 2009, Genes & development.

[28]  C. Vaslet,et al.  Hypothalamic Sirt1 Regulates Food Intake in a Rodent Model System , 2009, PloS one.

[29]  Shu-Chen Lu,et al.  Resveratrol is Not a Direct Activator of SIRT1 Enzyme Activity , 2009, Chemical biology & drug design.

[30]  R. Coppari,et al.  Central administration of resveratrol improves diet-induced diabetes. , 2009, Endocrinology.

[31]  T. Osborne,et al.  Evolutionary conservation and adaptation in the mechanism that regulates SREBP action: what a long, strange tRIP it's been. , 2009, Genes & development.

[32]  T. Veenstra,et al.  FXR acetylation is normally dynamically regulated by p300 and SIRT1 but constitutively elevated in metabolic disease states. , 2009, Cell metabolism.

[33]  A. Hofman,et al.  SIRT1 Genetic Variation Is Related to BMI and Risk of Obesity , 2009, Diabetes.

[34]  Jae-Won Jung,et al.  CK2 Is the Regulator of SIRT1 Substrate-Binding Affinity, Deacetylase Activity and Cellular Response to DNA-Damage , 2009, PloS one.

[35]  D. Sinclair,et al.  The ageing epigenome: Damaged beyond repair? , 2009, Ageing Research Reviews.

[36]  P. Sassone-Corsi,et al.  Circadian Control of the NAD+ Salvage Pathway by CLOCK-SIRT1 , 2009, Science.

[37]  J. Takahashi,et al.  Circadian Clock Feedback Cycle Through NAMPT-Mediated NAD+ Biosynthesis , 2009, Science.

[38]  H. Wijnen.  A Circadian Loop asSIRTs Itself , 2009, Science.

[39]  A. Salminen,et al.  Regulation of the aging process by autophagy. , 2009, Trends in molecular medicine.

[40]  P. Puigserver,et al.  AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity , 2009, Nature.

[41]  Qing Xu,et al.  Hepatocyte-specific deletion of SIRT1 alters fatty acid metabolism and results in hepatic steatosis and inflammation. , 2009, Cell metabolism.

[42]  O. Froy,et al.  High-fat diet delays and fasting advances the circadian expression of adiponectin signaling components in mouse liver. , 2009, Endocrinology.

[43]  W. Minor,et al.  Phosphorylation Regulates SIRT1 Function , 2008, PLoS ONE.

[44]  J. Olefsky,et al.  SIRT1 Exerts Anti-Inflammatory Effects and Improves Insulin Sensitivity in Adipocytes , 2008, Molecular and Cellular Biology.

[45]  J. Auwerx,et al.  Specific SIRT1 activation mimics low energy levels and protects against diet-induced metabolic disorders by enhancing fat oxidation. , 2008, Cell metabolism.

[46]  M. Ridderstråle,et al.  Polymorphisms in the adiponutrin gene are associated with increased insulin secretion and obesity. , 2008, European journal of endocrinology.

[47]  N. Torres,et al.  White adipose tissue as endocrine organ and its role in obesity. , 2008, Archives of medical research.

[48]  A. Chawla,et al.  Mechanisms of macrophage activation in obesity-induced insulin resistance , 2008, Nature Clinical Practice Endocrinology &Metabolism.

[49]  Alexander S Banks,et al.  SirT1 gain of function increases energy efficiency and prevents diabetes in mice. , 2008, Cell metabolism.

[50]  W. Hul,et al.  Association of SIRT1 gene variation with visceral obesity , 2008, Human Genetics.

[51]  J. Yates,et al.  A Fasting Inducible Switch Modulates Gluconeogenesis Via Activator-Coactivator Exchange , 2008, Nature.

[52]  Jiandie D. Lin,et al.  Genome-wide coactivation analysis of PGC-1alpha identifies BAF60a as a regulator of hepatic lipid metabolism. , 2008, Cell metabolism.

[53]  Florian Kreppel,et al.  SIRT1 Regulates Circadian Clock Gene Expression through PER2 Deacetylation , 2008, Cell.

[54]  Paolo Sassone-Corsi,et al.  The NAD+-Dependent Deacetylase SIRT1 Modulates CLOCK-Mediated Chromatin Remodeling and Circadian Control , 2008, Cell.

[55]  Fan Lan,et al.  SIRT1 Regulates Hepatocyte Lipid Metabolism through Activating AMP-activated Protein Kinase* , 2008, Journal of Biological Chemistry.

[56]  P. Pfluger,et al.  Sirt1 protects against high-fat diet-induced metabolic damage , 2008, Proceedings of the National Academy of Sciences.

[57]  F. Alt,et al.  Tissue-specific regulation of SIRT1 by calorie restriction. , 2008, Genes & development.

[58]  E. Mariman,et al.  The secretory function of adipocytes in the physiology of white adipose tissue , 2008, Journal of cellular physiology.

[59]  Vidya Subramanian,et al.  Alternative M2 activation of Kupffer cells by PPARdelta ameliorates obesity-induced insulin resistance. , 2008, Cell metabolism.

[60]  Peter Tontonoz,et al.  Fat and beyond: the diverse biology of PPARgamma. , 2008, Annual review of biochemistry.

[61]  I. Rahman,et al.  Sirt1, an Antiinflammatory and Antiaging Protein, Is Decreased in Lungs of Patients with Chronic Obstructive Pulmonary Disease at a Glance Commentary , 2022 .

[62]  F. Zipp,et al.  Sirt1 contributes critically to the redox-dependent fate of neural progenitors , 2008, Nature Cell Biology.

[63]  M. McBurney,et al.  SirT1 Regulates Energy Metabolism and Response to Caloric Restriction in Mice , 2008, PloS one.

[64]  Nicholas E. Bruns,et al.  A role for the NAD-dependent deacetylase Sirt1 in the regulation of autophagy , 2008, Proceedings of the National Academy of Sciences.

[65]  J. Qin,et al.  Negative regulation of the deacetylase SIRT1 by DBC1 , 2008, Nature.

[66]  Junjie Chen,et al.  DBC1 is a negative regulator of SIRT1 , 2008, Nature.

[67]  F. Alt,et al.  Tissue-specific regulation of SIRT 1 by calorie restriction , 2008 .

[68]  Andrew D. Steele,et al.  SIRT1 transgenic mice show phenotypes resembling calorie restriction , 2007, Aging cell.

[69]  Amy V. Lynch,et al.  Small molecule activators of SIRT1 as therapeutics for the treatment of type 2 diabetes , 2007, Nature.

[70]  J. Auwerx,et al.  DisSIRTing on LXR and cholesterol metabolism. , 2007, Cell metabolism.

[71]  Kathryn Moynihan Ramsey,et al.  High-fat diet disrupts behavioral and molecular circadian rhythms in mice. , 2007, Cell metabolism.

[72]  S. Nicosia,et al.  SIRT1 sumoylation regulates its deacetylase activity and cellular response to genotoxic stress , 2007, Nature Cell Biology.

[73]  Active regulator of SIRT1 cooperates with SIRT1 and facilitates suppression of p53 activity. , 2007, Molecular cell.

[74]  L. Guarente,et al.  SIRT1 deacetylates and positively regulates the nuclear receptor LXR. , 2007, Molecular cell.

[75]  P. Puigserver,et al.  Fasting-dependent glucose and lipid metabolic response through hepatic sirtuin 1 , 2007, Proceedings of the National Academy of Sciences.

[76]  Frank Brombacher,et al.  Macrophage-specific PPARγ controls alternative activation and improves insulin resistance , 2007, Nature.

[77]  Jan Nedergaard,et al.  Myogenic gene expression signature establishes that brown and white adipocytes originate from distinct cell lineages , 2007, Proceedings of the National Academy of Sciences.

[78]  P. Puigserver,et al.  Resveratrol Improves Mitochondrial Function and Protects against Metabolic Disease by Activating SIRT1 and PGC-1α , 2006, Cell.

[79]  G. Hotamisligil,et al.  Inflammation and metabolic disorders , 2006, Nature.

[80]  L. Guarente.  Sirtuins as potential targets for metabolic syndrome , 2006, Nature.

[81]  P. Puigserver,et al.  Resveratrol improves health and survival of mice on a high-calorie diet , 2006, Nature.

[82]  Michael W Young,et al.  Interplay of circadian clocks and metabolic rhythms. , 2006, Annual review of genetics.

[83]  M. W. Schwartz,et al.  Central nervous system control of food intake and body weight , 2006, Nature.

[84]  A. Goldfine,et al.  Inflammation and insulin resistance. , 2006, The Journal of clinical investigation.

[85]  C. Ahn,et al.  Comparison of Body Fat Composition and Serum Adiponectin Levels in Diabetic Obesity and Non‐diabetic Obesity , 2006, Obesity.

[86]  Paolo Sassone-Corsi,et al.  Circadian Regulator CLOCK Is a Histone Acetyltransferase , 2006, Cell.

[87]  S. Grundy.  Drug therapy of the metabolic syndrome: minimizing the emerging crisis in polypharmacy , 2006, Nature Reviews Drug Discovery.

[88]  L. Guarente,et al.  Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast , 2006, PLoS genetics.

[89]  Andrew D. Steele,et al.  Increase in Activity During Calorie Restriction Requires Sirt1 , 2005, Science.

[90]  S. Fields,et al.  Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast , 2005, PLoS Genetics.

[91]  Emilio Clementi,et al.  Calorie Restriction Promotes Mitochondrial Biogenesis by Inducing the Expression of eNOS , 2005, Science.

[92]  R. Evans,et al.  A Nuclear Receptor Atlas: macrophage activation. , 2005, Molecular endocrinology.

[93]  Fred W. Turek,et al.  Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice , 2005, Science.

[94]  L. Guarente,et al.  Calorie restriction, SIRT1 and metabolism: understanding longevity , 2005, Nature Reviews Molecular Cell Biology.

[95]  Wilhelm Haas,et al.  Nutrient control of glucose homeostasis through a complex of PGC-1α and SIRT1 , 2005, Nature.

[96]  S. Grundy,et al.  The metabolic syndrome , 2003, The Lancet.

[97]  G. Berghe.  The role of the liver in metabolic homeostasis: Implications for inborn errors of metabolism , 1991, Journal of Inherited Metabolic Disease.

[98]  Steven P Gygi,et al.  Nutrient control of glucose homeostasis through a complex of PGC-1alpha and SIRT1. , 2005, Nature.

[99]  B. Rogina,et al.  Sir2 mediates longevity in the fly through a pathway related to calorie restriction. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[100]  Satchidananda Panda,et al.  BMAL1 and CLOCK, Two Essential Components of the Circadian Clock, Are Involved in Glucose Homeostasis , 2004, PLoS biology.

[101]  D. Reinberg,et al.  Human SirT1 interacts with histone H1 and promotes formation of facultative heterochromatin. , 2004, Molecular cell.

[102]  A. Gressner,et al.  Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. , 2004, Clinical chemistry.

[103]  Namjin Chung,et al.  Sirt1 promotes fat mobilization in white adipocytes by repressing PPAR-γ , 2004, Nature.

[104]  M. Mayo,et al.  Modulation of NF‐κB‐dependent transcription and cell survival by the SIRT1 deacetylase , 2004, The EMBO journal.

[105]  K. Flegal,et al.  Prevalence of overweight and obesity among US children, adolescents, and adults, 1999-2002. , 2004, JAMA.

[106]  L. Guarente,et al.  The Sir2 family of protein deacetylases. , 2004, Annual review of biochemistry.

[107]  S. Klein,et al.  Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[108]  M. Lazar,et al.  The current biology of resistin , 2004, Journal of internal medicine.

[109]  G. Barish,et al.  PPARs and the complex journey to obesity , 2004, Nature Medicine.

[110]  Delin Chen,et al.  Mammalian SIRT1 Represses Forkhead Transcription Factors , 2004, Cell.

[111]  Phuong Chung,et al.  Small molecule activators of sirtuins extend Saccharomyces cerevisiae lifespan , 2003, Nature.

[112]  R. Weindruch,et al.  Influence of age and caloric restriction on liver glycolytic enzyme activities and metabolite concentrations in mice , 2003, Experimental Gerontology.

[113]  Matthias Blüher,et al.  Extended Longevity in Mice Lacking the Insulin Receptor in Adipose Tissue , 2003, Science.

[114]  S. Gordon.  Alternative activation of macrophages , 2003, Nature Reviews Immunology.

[115]  P. Defossez,et al.  Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae. , 2000, Science.

[116]  J. Boeke,et al.  A phylogenetically conserved NAD+-dependent protein deacetylase activity in the Sir2 protein family. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[117]  R. Sternglanz,et al.  The silencing protein SIR2 and its homologs are NAD-dependent protein deacetylases. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[118]  S. Woods,et al.  Central nervous system control of food intake , 2000, Nature.

[119]  L. Guarente,et al.  Transcriptional silencing and longevity protein Sir2 is an NAD-dependent histone deacetylase , 2000, Nature.

[120]  R. Evans,et al.  The RXR heterodimers and orphan receptors , 1995, Cell.

[121]  G. van den Berghe.  The role of the liver in metabolic homeostasis: implications for inborn errors of metabolism. , 1991, Journal of inherited metabolic disease.