Roger Unger

Summary

Affiliation: University of Texas Southwestern Medical Center
Country: USA

Publications

  1. ncbi request reprint Lipotoxic diseases
    Roger H Unger
    Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    Annu Rev Med 53:319-36. 2002
  2. ncbi request reprint Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine
    Roger H Unger
    Internal Medicine, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 8854, USA
    Biochimie 87:57-64. 2005
  3. ncbi request reprint Metabolic mechanisms of failure of intraportally transplanted pancreatic beta-cells in rats: role of lipotoxicity and prevention by leptin
    Young Lee
    Gifford Laboratories of the Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    Diabetes 56:2295-301. 2007
  4. pmc Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice
    Young Lee
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Diabetes 60:391-7. 2011
  5. pmc Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    J Clin Invest 122:4-12. 2012
  6. ncbi request reprint Hyperleptinemia: protecting the heart from lipid overload
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Hypertension 45:1031-4. 2005
  7. doi request reprint Reinventing type 2 diabetes: pathogenesis, treatment, and prevention
    Roger H Unger
    Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, and Veterans Affairs Medical Center, Dallas, Texas 75390 8854, USA
    JAMA 299:1185-7. 2008
  8. ncbi request reprint Lipid overload and overflow: metabolic trauma and the metabolic syndrome
    Roger H Unger
    University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Trends Endocrinol Metab 14:398-403. 2003
  9. ncbi request reprint Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome
    Roger H Unger
    Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Y8 212, Dallas, Texas 75390 8854, USA
    Endocrinology 144:5159-65. 2003
  10. doi request reprint Lipid homeostasis, lipotoxicity and the metabolic syndrome
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine at the University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Biochim Biophys Acta 1801:209-14. 2010

Research Grants

Collaborators

Detail Information

Publications43

  1. ncbi request reprint Lipotoxic diseases
    Roger H Unger
    Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    Annu Rev Med 53:319-36. 2002
    ..There is now substantial evidence that complications of human obesity may reflect lipotoxicity similar to that described in rodents...
  2. ncbi request reprint Longevity, lipotoxicity and leptin: the adipocyte defense against feasting and famine
    Roger H Unger
    Internal Medicine, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Dallas, TX 75390 8854, USA
    Biochimie 87:57-64. 2005
    ....
  3. ncbi request reprint Metabolic mechanisms of failure of intraportally transplanted pancreatic beta-cells in rats: role of lipotoxicity and prevention by leptin
    Young Lee
    Gifford Laboratories of the Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    Diabetes 56:2295-301. 2007
    ..Graft failure is prevented by blocking lipogenesis. The results suggest that strict antilipogenic intervention might improve outcomes after human islet transplantation...
  4. pmc Glucagon receptor knockout prevents insulin-deficient type 1 diabetes in mice
    Young Lee
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA
    Diabetes 60:391-7. 2011
    ..To determine the role of glucagon action in the metabolic phenotype of untreated insulin deficiency...
  5. pmc Glucagonocentric restructuring of diabetes: a pathophysiologic and therapeutic makeover
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    J Clin Invest 122:4-12. 2012
    ..This indicates that glucagon suppression or inactivation may provide therapeutic advantages over insulin monotherapy...
  6. ncbi request reprint Hyperleptinemia: protecting the heart from lipid overload
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Hypertension 45:1031-4. 2005
    ..The causes of failure of this system and its clinical consequences are discussed...
  7. doi request reprint Reinventing type 2 diabetes: pathogenesis, treatment, and prevention
    Roger H Unger
    Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, and Veterans Affairs Medical Center, Dallas, Texas 75390 8854, USA
    JAMA 299:1185-7. 2008
  8. ncbi request reprint Lipid overload and overflow: metabolic trauma and the metabolic syndrome
    Roger H Unger
    University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Trends Endocrinol Metab 14:398-403. 2003
    ..Third, I suggest that lipid-induced insulin resistance and the accompanying metabolic syndrome are secondary to leptin resistance, resulting in breakdown in the normal partitioning of surplus lipids in the adipocyte compartment...
  9. ncbi request reprint Minireview: weapons of lean body mass destruction: the role of ectopic lipids in the metabolic syndrome
    Roger H Unger
    Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Y8 212, Dallas, Texas 75390 8854, USA
    Endocrinology 144:5159-65. 2003
    ..Increased lipid content in the heart and skeletal muscle organs of such patients is now under study...
  10. doi request reprint Lipid homeostasis, lipotoxicity and the metabolic syndrome
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine at the University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Biochim Biophys Acta 1801:209-14. 2010
    ..Fatty acid derivatives can interfere with the function of the cell and ultimately lead to its demise through lipoapoptosis, the consequences of which are gradual organ failure...
  11. pmc Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity
    Roger H Unger
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Touchstone Center for Diabetes Research, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Trends Endocrinol Metab 21:345-52. 2010
    ..Metabolic syndrome is ascribed to lipotoxicity caused by age-related resistance to antilipotoxic protection by leptin...
  12. pmc Noninvasive tracking of gene expression by reporter transgene imaging
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Proc Natl Acad Sci U S A 105:12641-2. 2008
  13. ncbi request reprint Lipoapoptosis: its mechanism and its diseases
    Roger H Unger
    Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Biochim Biophys Acta 1585:202-12. 2002
    ....
  14. ncbi request reprint The physiology of cellular liporegulation
    Roger H Unger
    Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    Annu Rev Physiol 65:333-47. 2003
    ..We speculate that the metabolic syndrome may be the human equivalent of the lipotoxic syndrome of rodents...
  15. pmc Paracrinology of islets and the paracrinopathy of diabetes
    Roger H Unger
    Department of Internal Medicine, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 107:16009-12. 2010
    ..These results have considerable medical implications, as they suggest new approaches to normalize the extreme volatility of glycemia in diabetic patients...
  16. ncbi request reprint Increased expression and activity of 11beta-HSD-1 in diabetic islets and prevention with troglitazone
    Laurence Duplomb
    Gifford Laboratories, Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Biochem Biophys Res Commun 313:594-9. 2004
    ..We conclude that 11beta-HSD-1 expression and activity are increased in islets of diabetic, but not prediabetic ZDF rats, and that TGZ prevents both the increase in 11beta-HSD-1 and the diabetes...
  17. pmc Fat storage in adipocytes requires inactivation of leptin's paracrine activity: implications for treatment of human obesity
    May Yun Wang
    Gifford Laboratories, Touchstone Center for Diabetes Research and Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, 75390 8854, USA
    Proc Natl Acad Sci U S A 102:18011-6. 2005
    ..In conclusion, storage of surplus calories in WAT and the development of diet-induced obesity require the blockade of a latent leptin-stimulated caloric sump in white adipocytes...
  18. ncbi request reprint Cardiac steatosis in diabetes mellitus: a 1H-magnetic resonance spectroscopy study
    Jonathan M McGavock
    Department of Internal Medicine, Divisions of Hypertension, University of Texas Southwestern Medical Center at Dallas, Dallas, Tex, USA
    Circulation 116:1170-5. 2007
    ..Whether cardiac steatosis precedes the onset of cardiomyopathy in individuals with impaired glucose tolerance or in patients with type 2 diabetes mellitus is unknown...
  19. pmc Adipogenic capacity and the susceptibility to type 2 diabetes and metabolic syndrome
    May Yun Wang
    Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Proc Natl Acad Sci U S A 105:6139-44. 2008
    ..These results suggest that the expression level of genes that regulate the adipogenic response to overnutrition profoundly influences the age of onset and severity of diet-induced type 2 diabetes and co-morbidities...
  20. pmc Leptin therapy in insulin-deficient type I diabetes
    May Yun Wang
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 107:4813-9. 2010
    ..The results imply that leptin administration may have multiple short- and long-term advantages over insulin monotherapy for type 1 diabetes...
  21. ncbi request reprint Gene expression profile of rat adipose tissue at the onset of high-fat-diet obesity
    Jinping Li
    Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    Am J Physiol Endocrinol Metab 282:E1334-41. 2002
    ..The only one of these thus far characterized functionally was found to promote lipogenesis...
  22. ncbi request reprint Movin' on up: adipocytes become regulators of nutrient homeostasis
    Roger H Unger
    Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    Cell Metab 3:147-8. 2006
    ..2006[this issue of Cell Metabolism]) unexpectedly induce leptin sensitivity with hypophagia and improvement in abnormal glucose and lipid abnormalities...
  23. pmc Noninvasive quantification of pancreatic fat in humans
    Ildiko Lingvay
    Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA
    J Clin Endocrinol Metab 94:4070-6. 2009
    ....
  24. ncbi request reprint Combined leptin actions on adipose tissue and hypothalamus are required to deplete adipocyte fat in lean rats: implications for obesity treatment
    Byung Hyun Park
    Gifford Laboratories of the Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, Texas 75390 8854, USA
    J Biol Chem 281:40283-91. 2006
    ....
  25. ncbi request reprint Effects of leptin, troglitazone, and dietary fat on stearoyl CoA desaturase
    Tetsuya Kakuma
    Department of Internal Medicine, Gifford Laboratories, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Biochem Biophys Res Commun 297:1259-63. 2002
    ..The findings suggest that leptin controls SCD-1 expression and that troglitazone's antilipotoxic action may involve SCD-2 upregulation...
  26. ncbi request reprint Role of PP2C in cardiac lipid accumulation in obese rodents and its prevention by troglitazone
    May Yun Wang
    Department of Internal Medicine, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA
    Am J Physiol Endocrinol Metab 288:E216-21. 2005
    ..Our findings highlight a role of PP2C and AMPK in the derangements of cardiac lipid metabolism in obesity and provide new insights as to the mechanisms of the liporegulatory disorder leading to lipotoxic cardiomyopathy...
  27. ncbi request reprint Forgotten but not gone: the rediscovery of fatty heart, the most common unrecognized disease in America
    Lidia S Szczepaniak
    Department of Internal Medicine, Division of Hypertension, University of Texas Southwestern Medical Center at Dallas, 5323 Harry Hines Blvd, Dallas, TX 75390, USA
    Circ Res 101:759-67. 2007
    ....
  28. ncbi request reprint Demonstration of reverse fatty acid transport from rat cardiomyocytes
    Byung Hyun Park
    Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    J Lipid Res 45:1992-9. 2004
    ..Perfusion with insulin increased FA release by 32%. In vitro and ex vivo findings suggest that nonadipose tissues such as myocardium can export FA when the unoxidized lipid content is excessive...
  29. pmc Fatty diabetic lung: altered alveolar structure and surfactant protein expression
    David J Foster
    Pulmonary and Critical Care Medicine, Department of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd, Dallas, TX 75390 9034, USA
    Am J Physiol Lung Cell Mol Physiol 298:L392-403. 2010
    ....
  30. pmc Hyperleptinemia prevents lipotoxic cardiomyopathy in acyl CoA synthase transgenic mice
    Young Lee
    Gifford Laboratories, Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Proc Natl Acad Sci U S A 101:13624-9. 2004
    ..We conclude that obesity-level hyperleptinemia protects the heart from lipotoxicity...
  31. ncbi request reprint Independence of hyperleptinemia-induced fat disappearance from thyroid hormone
    Laurence Duplomb
    Gifford Laboratories, Department of Internal Medicine, Center for Diabetes Research, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390, USA
    Biochem Biophys Res Commun 323:49-51. 2004
    ..We conclude that the fat-wasting effect of sustained hyperleptinemia does not involve "local hyperthyroidism" in white adipose tissue and does not require thyroid hormone...
  32. pmc Hepatic insig-1 or -2 overexpression reduces lipogenesis in obese Zucker diabetic fatty rats and in fasted/refed normal rats
    Kiyosumi Takaishi
    Gifford Laboratories, Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Proc Natl Acad Sci U S A 101:7106-11. 2004
    ..However, the increase in endogenous insig-1 expression associated with augmented lipogenesis may limit it, but is insufficient to prevent it...
  33. ncbi request reprint Myocardial triglycerides and systolic function in humans: in vivo evaluation by localized proton spectroscopy and cardiac imaging
    Lidia S Szczepaniak
    Department of Internal Medicine, University of Texas, Southwestern Medical Center at Dallas, USA
    Magn Reson Med 49:417-23. 2003
    ..Increased myocardial triglyceride content was accompanied by elevated LV mass and suppressed septal wall thickening as measured by cardiac imaging...
  34. ncbi request reprint Alpha-lipoic acid prevents lipotoxic cardiomyopathy in acyl CoA-synthase transgenic mice
    Young Lee
    Gifford Laboratories, Touchstone Center for Diabetes Research, University of Texas, Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Biochem Biophys Res Commun 344:446-52. 2006
    ..Since food restriction did not prevent lipotoxicity, we conclude that alpha-LA treatment, like hyperleptinemia, protects the heart of ACS-transgenic mice from lipotoxicity...
  35. pmc Insig-1 "brakes" lipogenesis in adipocytes and inhibits differentiation of preadipocytes
    Jinping Li
    Touchstone Center for Diabetes Research, University of Texas Southwestern Medical Center and Veterans Affairs Medical Center, Dallas, TX 75390, USA
    Proc Natl Acad Sci U S A 100:9476-81. 2003
    ..The results suggest that insig-1 expression restricts lipogenesis in mature adipocytes and blocks differentiation in preadipocytes...
  36. ncbi request reprint Diabetes and apoptosis: lipotoxicity
    Christine M Kusminski
    Department of Internal Medicine, Touchstone Diabetes Center, University of Texas Southwestern Medical Center, Dallas, TX 75390 8549, USA
    Apoptosis 14:1484-95. 2009
    ..Here, we focus on how both of these processes affect metabolically significant cell-types and highlight how lipotoxicity and sequential lipoapoptosis are as major mediators of insulin resistance, diabetes and cardiovascular disease...
  37. ncbi request reprint The hyperleptinemia of obesity-regulator of caloric surpluses
    Roger H Unger
    Touchstone Center for Diabetes Research, Department of Internal Medicine, UT Southwestern Medical Center at Dallas, 5323 Harry Hines Boulevard, Y8 212, Dallas, TX 75390, USA
    Cell 117:145-6. 2004
    ..This preview examines AMP biology and its role in malonyl-CoA generation and attempts to integrate its central actions with its peripheral antilipotoxic actions within the context of leptin physiology in obesity...
  38. pmc Making insulin-deficient type 1 diabetic rodents thrive without insulin
    Xinxin Yu
    Touchstone Center for Diabetes Research, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390 8854, USA
    Proc Natl Acad Sci U S A 105:14070-5. 2008
    ....
  39. ncbi request reprint Adiposity of the heart, revisited
    Jonathan M McGavock
    University of Texas Southwestern Medical Center, Dallas, Texas 75390 8899, USA
    Ann Intern Med 144:517-24. 2006
    ..These studies parallel the observations in obese animals and provide evidence that myocardial lipid content may be a biomarker and putative therapeutic target for cardiac disease in obese patients...
  40. ncbi request reprint Effects of leptin on endothelial function with OB-Rb gene transfer in Zucker fatty rats
    Xueqing Jin
    Second Department of Internal Medicine, Nihon University School of Medicine, Tokyo 173 8610, Japan
    Atherosclerosis 169:225-33. 2003
    ..Ad.LacZ did not influence the angiogenic effects of leptin. The impaired endothelial function with the leptin resistance may be one of causes of the atherosclerosis in the metabolic syndrome...
  41. ncbi request reprint Biochemical mechanism of lipid-induced impairment of glucose-stimulated insulin secretion and reversal with a malate analogue
    Anne Boucher
    Sarah W Stedman Nutrition and Metabolism Center and Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA
    J Biol Chem 279:27263-71. 2004
    ..We conclude that chronic exposure of islet beta-cells to fatty acids grossly alters a mitochondrial pathway of pyruvate metabolism that is important for normal GSIS...
  42. pmc Rapid transformation of white adipocytes into fat-oxidizing machines
    Lelio Orci
    Department of Morphology, University of Geneva Medical School, Rue Michel Servet 1, CH 1211 Geneva 4, Switzerland
    Proc Natl Acad Sci U S A 101:2058-63. 2004
    ..The ability to transform adipocytes into unique fat-burning cells may suggest novel therapeutic strategies for obesity...
  43. ncbi request reprint Klotho-induced insulin resistance: a blessing in disguise?
    Roger H Unger
    Nat Med 12:56-7. 2006

Research Grants14

  1. The Glucoregulatory and Liporegulatory Peptide Hormones
    Roger Unger; Fiscal Year: 2007
    ..FA-depletion of pancreatic islet transplants makes them resistant to rejection. Using FA-depleted islets we have been able to "cure" insulin-deficient diabetes in rats for ~1 year without immunosuppression. ..
  2. GLUCOREGULATORY PEPTIDE HORMONES
    Roger Unger; Fiscal Year: 2001
    ..The studies should indicate the mechanisms by which FFA cause compensatory changes in beta-cells in the early years of obesity but cause dysfunction apoptosis of beta-cells, and diabetes, in the late years. ..
  3. The Glucoregulatory and Liporegulatory Peptide Hormones
    Roger Unger; Fiscal Year: 2002
    ..The result is a massive expansion of adipocytes, which is required for severe obesity to develop. Understanding this pathway is the first step in attempting to block the development of this common American health problem. ..
  4. The Glucoregulatory and Liporegulatory Peptide Hormones
    Roger Unger; Fiscal Year: 2006
    ..FA-depletion of pancreatic islet transplants makes them resistant to rejection. Using FA-depleted islets we have been able to "cure" insulin-deficient diabetes in rats for ~1 year without immunosuppression. ..
  5. The Glucoregulatory and Liporegulatory Peptide Hormones
    Roger Unger; Fiscal Year: 2004
    ..The result is a massive expansion of adipocytes, which is required for severe obesity to develop. Understanding this pathway is the first step in attempting to block the development of this common American health problem. ..
  6. The Glucoregulatory and Liporegulatory Peptide Hormones
    Roger Unger; Fiscal Year: 2003
    ..The result is a massive expansion of adipocytes, which is required for severe obesity to develop. Understanding this pathway is the first step in attempting to block the development of this common American health problem. ..
  7. GLUCOREGULATORY PEPTIDE HORMONES
    Roger Unger; Fiscal Year: 2000
    ..The studies should indicate the mechanisms by which FFA cause compensatory changes in beta-cells in the early years of obesity but cause dysfunction apoptosis of beta-cells, and diabetes, in the late years. ..
  8. GLUCOREGULATORY PEPTIDE HORMONES
    Roger Unger; Fiscal Year: 1999
    ..The studies should indicate the mechanisms by which FFA cause compensatory changes in beta-cells in the early years of obesity but cause dysfunction apoptosis of beta-cells, and diabetes, in the late years. ..