PHILIP SCARPACE

Summary

Affiliation: University of Florida
Country: USA

Publications

  1. ncbi request reprint Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss
    Gang Li
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610, USA
    Am J Physiol Endocrinol Metab 293:E252-8. 2007
  2. ncbi request reprint Elevated leptin: consequence or cause of obesity?
    Philip J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610, USA
    Front Biosci 12:3531-44. 2007
  3. pmc Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged leptin action in either region cross-desensitizes
    P J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA
    Neuropharmacology 65:90-100. 2013
  4. pmc Wheel running eliminates high-fat preference and enhances leptin signaling in the ventral tegmental area
    P J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, United States
    Physiol Behav 100:173-9. 2010
  5. pmc Leptin resistance: a prediposing factor for diet-induced obesity
    Philip J Scarpace
    Dept of Pharmacology and Therapeutics, Univ of Florida, Gainesville, FL 32610, USA
    Am J Physiol Regul Integr Comp Physiol 296:R493-500. 2009
  6. ncbi request reprint Leptin antagonist reveals an uncoupling between leptin receptor signal transducer and activator of transcription 3 signaling and metabolic responses with central leptin resistance
    Philip J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA
    J Pharmacol Exp Ther 320:706-12. 2007
  7. ncbi request reprint Modulation of uncoupling protein 2 and uncoupling protein 3: regulation by denervation, leptin and retinoic acid treatment
    P J Scarpace
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608 1197, USA
    J Endocrinol 164:331-7. 2000
  8. ncbi request reprint Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats
    P J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA
    Diabetologia 48:1075-83. 2005
  9. ncbi request reprint Leptin-induced leptin resistant rats exhibit enhanced responses to the melanocortin agonist MT II
    Philip J Scarpace
    Geriatric Research, Education and Clinical Center 182, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Neuropharmacology 45:211-9. 2003
  10. ncbi request reprint Uncoupling proteins 2 and 3 with age: regulation by fasting and beta3-adrenergic agonist treatment
    P J Scarpace
    Geriatric Research, Education and Clinical Center, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, Florida 32608 1197, USA
    J Gerontol A Biol Sci Med Sci 55:B588-92. 2000

Research Grants

  1. Leptin resistance: 1 mechanism underlying age-related obesity
    PHILIP SCARPACE; Fiscal Year: 2007
  2. Age-related Obesity: Interventions with Gene Delivery
    PHILIP SCARPACE; Fiscal Year: 2006
  3. IMPAIRED LEPTIN RESPONSIVENESS WITH AGE
    PHILIP SCARPACE; Fiscal Year: 2002

Collaborators

Detail Information

Publications36

  1. ncbi request reprint Melanocortin activation of nucleus of the solitary tract avoids anorectic tachyphylaxis and induces prolonged weight loss
    Gang Li
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida 32610, USA
    Am J Physiol Endocrinol Metab 293:E252-8. 2007
    ....
  2. ncbi request reprint Elevated leptin: consequence or cause of obesity?
    Philip J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610, USA
    Front Biosci 12:3531-44. 2007
    ..Once leptin resistance takes hold, each subsequent exposure to high-density food faces diminished counter-regulatory responses, leading to exacerbated weight gain...
  3. pmc Leptin overexpression in VTA trans-activates the hypothalamus whereas prolonged leptin action in either region cross-desensitizes
    P J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA
    Neuropharmacology 65:90-100. 2013
    ....
  4. pmc Wheel running eliminates high-fat preference and enhances leptin signaling in the ventral tegmental area
    P J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL 32610, United States
    Physiol Behav 100:173-9. 2010
    ..Moreover, WR enhances leptin signaling specifically in the VTA, suggestive of a WR-evoked mechanism of heightened leptin function in the VTA to curb the drive to consume palatable HF foods...
  5. pmc Leptin resistance: a prediposing factor for diet-induced obesity
    Philip J Scarpace
    Dept of Pharmacology and Therapeutics, Univ of Florida, Gainesville, FL 32610, USA
    Am J Physiol Regul Integr Comp Physiol 296:R493-500. 2009
    ..Moreover, once leptin resistance takes hold, it aggravates DIO, and the leptin resistance and obesity compound one another, promoting a vicious cycle of escalating weight gain...
  6. ncbi request reprint Leptin antagonist reveals an uncoupling between leptin receptor signal transducer and activator of transcription 3 signaling and metabolic responses with central leptin resistance
    Philip J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, FL 32610, USA
    J Pharmacol Exp Ther 320:706-12. 2007
    ..These data reveal an uncoupling between leptin receptor activation and metabolic responses with central leptin resistance...
  7. ncbi request reprint Modulation of uncoupling protein 2 and uncoupling protein 3: regulation by denervation, leptin and retinoic acid treatment
    P J Scarpace
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608 1197, USA
    J Endocrinol 164:331-7. 2000
    ....
  8. ncbi request reprint Leptin resistance exacerbates diet-induced obesity and is associated with diminished maximal leptin signalling capacity in rats
    P J Scarpace
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, FL, USA
    Diabetologia 48:1075-83. 2005
    ..We assessed maximal leptin-mediated binding of the transcription factor signal transducer and activator of transcription 3 (STAT3), and the response to high-fat feeding in lean leptin-resistant rats...
  9. ncbi request reprint Leptin-induced leptin resistant rats exhibit enhanced responses to the melanocortin agonist MT II
    Philip J Scarpace
    Geriatric Research, Education and Clinical Center 182, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Neuropharmacology 45:211-9. 2003
    ..We suggest that defective endogenous melanocortin activation may represent one element of leptin resistance, leading to compensatory hypersensitivity of the melanocortin pathway...
  10. ncbi request reprint Uncoupling proteins 2 and 3 with age: regulation by fasting and beta3-adrenergic agonist treatment
    P J Scarpace
    Geriatric Research, Education and Clinical Center, Malcom Randall Department of Veterans Affairs Medical Center, Gainesville, Florida 32608 1197, USA
    J Gerontol A Biol Sci Med Sci 55:B588-92. 2000
    ....
  11. ncbi request reprint Impaired leptin signal transduction with age-related obesity
    P J Scarpace
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, FL, Gainesville 32608 1197, USA
    Neuropharmacology 39:1872-9. 2000
    ..This impaired leptin signal transduction may be due to either the elevated obesity with age or due to age itself or both...
  12. ncbi request reprint Central leptin gene delivery evokes persistent leptin signal transduction in young and aged-obese rats but physiological responses become attenuated over time in aged-obese rats
    P J Scarpace
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608 1197, USA
    Neuropharmacology 42:548-61. 2002
    ....
  13. ncbi request reprint Peripheral and hypothalamic leptin resistance with age-related obesity
    P J Scarpace
    Geriatric Research, Education and Clinical Center 182, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Physiol Behav 74:721-7. 2001
    ..This leptin resistance may have both a peripheral and central component and may be due to either the elevated obesity and serum leptin with age or due to age itself or both...
  14. ncbi request reprint Hypothalamic leptin resistance is associated with impaired leptin signal transduction in aged obese rats
    P J Scarpace
    Geriatric Research, Education and Clinical Center, Malcom Randall Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Neuroscience 104:1111-7. 2001
    ..This impaired leptin signal transduction may be due either to the elevated obesity with age or to age itself, or to both...
  15. ncbi request reprint Leptin-induced leptin resistance reveals separate roles for the anorexic and thermogenic responses in weight maintenance
    Philip J Scarpace
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Endocrinology 143:3026-35. 2002
    ..We propose that both elevated leptin and obesity may be necessary for the development of leptin resistance...
  16. ncbi request reprint Central leptin gene therapy fails to overcome leptin resistance associated with diet-induced obesity
    Jared Wilsey
    Geriatric Research, Education and Clinical Center, Dept of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Am J Physiol Regul Integr Comp Physiol 285:R1011-20. 2003
    ..This suggests that central overexpression of leptin is not a viable strategy to reverse diet-induced obesity...
  17. ncbi request reprint Central pro-opiomelanocortin gene delivery results in hypophagia, reduced visceral adiposity, and improved insulin sensitivity in genetically obese Zucker rats
    Gang Li
    Department of Pharmacology and Therapeutics, University of Florida College of Medicine, Gainesville, Florida, USA
    Diabetes 52:1951-7. 2003
    ..The mechanisms may involve the sustained hypophagia and the augmentation of thermogenesis in BAT...
  18. pmc Nigrostriatal rAAV-mediated GDNF overexpression induces robust weight loss in a rat model of age-related obesity
    Fredric P Manfredsson
    Department of Neuroscience, Powell Gene Therapy Center, McKnight Brain Institute, University of Florida College of Medicine, Gainesville, Florida, USA
    Mol Ther 17:980-91. 2009
    ..Activation of these hypothalamic CRH neurons likely accounted for the observed metabolic effects leading to weight loss in obese rats...
  19. pmc Central overexpression of leptin antagonist reduces wheel running and underscores importance of endogenous leptin receptor activity in energy homeostasis
    Michael Matheny
    Department of Pharmacology and Therapeutic, University of Florida College of Medicine, Gainesville, Florida 32610, USA
    Am J Physiol Regul Integr Comp Physiol 297:R1254-61. 2009
    ..These findings underscore the critical role of unrestrained leptin receptor activity in long-term energy homeostasis and suggest that even minor disruption of leptin receptor function can promote obesity...
  20. pmc Sustained peripheral expression of transgene adiponectin offsets the development of diet-induced obesity in rats
    Stanislav Shklyaev
    Department of Molecular Genetics and Microbiology, Powell Gene Therapy Center, University of Florida, Gainesville, FL 32610 0266, USA
    Proc Natl Acad Sci U S A 100:14217-22. 2003
    ..These data show successful peripheral therapy in a clinically relevant model for human obesity and insulin resistance...
  21. pmc The soluble leptin receptor neutralizes leptin-mediated STAT3 signalling and anorexic responses in vivo
    Jiejin Zhang
    Department of Pharmacology and Therapeutics, University of Florida, Gainesville, Florida 32610, USA
    Br J Pharmacol 158:475-82. 2009
    ..Here we assessed the effects of the SLR on physiological responses to leptin, in vivo...
  22. ncbi request reprint Oral vanadium enhances the catabolic effects of central leptin in young adult rats
    Jared Wilsey
    Geriatric Research, Education, and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida 32608 1197, USA
    Endocrinology 147:493-501. 2006
    ....
  23. ncbi request reprint The role of leptin in leptin resistance and obesity
    Yi Zhang
    Research Service, Department of Veterans Affairs Medical Center, Gainesville, FL 32608, USA
    Physiol Behav 88:249-56. 2006
    ..In essence, the augmented leptin accompanying obesity contributes to leptin resistance, and this leptin resistance promotes further obesity, leading to a vicious cycle of escalating metabolic devastation...
  24. ncbi request reprint Aged-obese rats exhibit robust responses to a melanocortin agonist and antagonist despite leptin resistance
    Yi Zhang
    Department of Veterans Affairs Medical Center, Geriatric Research, Education and Clinical Center, Gainesville, FL 32608 1197, USA
    Neurobiol Aging 25:1349-60. 2004
    ..The equally strong orexigenic response to SHU9119 coupled with unaltered POMC expression and food intake in the young versus old suggest that melanocortin tone is unchanged with age despite impaired melanocortin activation by leptin...
  25. ncbi request reprint Repeated fasting/refeeding elevates plasma leptin without increasing fat mass in rats
    Yong Woon Kim
    Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Physiol Behav 78:459-64. 2003
    ....
  26. ncbi request reprint Synergy between leptin therapy and a seemingly negligible amount of voluntary wheel running prevents progression of dietary obesity in leptin-resistant rats
    Alexandra Shapiro
    Department of Pharmacology and Therapeutics, Box 100267, University of Florida College of Medicine, Gainesville, Florida 32610, USA
    Diabetes 57:614-22. 2008
    ..Second, we examined if voluntary wheel running is beneficial in reducing the trajectory of weight gain in high-fat-raised leptin-resistant rats...
  27. doi request reprint Effect of high-fat diet feeding on hypothalamic redox signaling and central blood pressure regulation
    Benedek Erdos
    Department of Veterans Affairs Medical Center, Geriatric Research, Education and Clinical Center, Gainesville, FL, USA
    Hypertens Res 32:983-8. 2009
    ....
  28. pmc Intermittent MTII application evokes repeated anorexia and robust fat and weight loss
    Yi Zhang
    Research Department, Malcom Randall Veterans Affairs Medical Center NF SG HSC, Rm E585 1, 1601 SW Archer Road, Gainesville, FL 32608, USA
    Peptides 31:639-43. 2010
    ..Either form of MTII administration results in significant weight and adiposity reductions, involving perhaps fatty acid oxidation within specific adipose tissues...
  29. pmc Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding
    Alexandra Shapiro
    Dept of Pharmacology and Therapeutics, Box 100267, Univ of Florida, Gainesville, Florida 32610, USA
    Am J Physiol Regul Integr Comp Physiol 295:R1370-5. 2008
    ..Our data indicate that chronic fructose consumption induces leptin resistance prior to body weight, adiposity, serum leptin, insulin, or glucose increases, and this fructose-induced leptin resistance accelerates high-fat induced obesity...
  30. ncbi request reprint Leptin antagonist reverses hypertension caused by leptin overexpression, but fails to normalize obesity-related hypertension
    Nihal Tumer
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida, USA
    J Hypertens 25:2471-8. 2007
    ..The present study employed a rat leptin antagonist to evaluate the role of elevated leptin in obesity-associated hypertension...
  31. pmc Effects of life-long caloric restriction and voluntary exercise on age-related changes in levels of catecholamine biosynthetic enzymes and angiotensin II receptors in the rat adrenal medulla and hypothalamus
    Benedek Erdos
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608, USA
    Exp Gerontol 42:745-52. 2007
    ..05). These data indicate that a small decrease in daily food intake can avert age-related changes in catecholamine biosynthetic enzyme levels in the adrenal medulla and hypothalamus, possibly through affecting angiotensin II signaling...
  32. ncbi request reprint Regulation of adiponectin and leptin gene expression in white and brown adipose tissues: influence of beta3-adrenergic agonists, retinoic acid, leptin and fasting
    Yi Zhang
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Biochim Biophys Acta 1584:115-22. 2002
    ..The long-term regulation of adiponectin expression in WAT appears to be the opposite of that of leptin and may be more sensitive to changes in adiposity or insulin sensitivity...
  33. ncbi request reprint Acute pressor effect of central angiotensin II is mediated by NAD(P)H-oxidase-dependent production of superoxide in the hypothalamic cardiovascular regulatory nuclei
    Benedek Erdos
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, Florida, USA
    J Hypertens 24:109-16. 2006
    ..Centrally applied angiotensin II (Ang II) increases sympathetic nervous activity and mean arterial blood pressure (MAP), but the mediation of these effects is not fully understood...
  34. ncbi request reprint Metformin restores responses to insulin but not to growth hormone in Sprague-Dawley rats
    Stephen E Borst
    VA Medical Center, Education and Clinical Center, Gainesville, Florida 32608, USA
    Biochem Biophys Res Commun 291:722-6. 2002
    ..The latter may, in part, be explained by the failure of metformin to prevent GH-induced elevation of TNF in visceral fat...
  35. ncbi request reprint Hypothalamic rAAV-mediated GDNF gene delivery ameliorates age-related obesity
    Nihal Tumer
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Neurobiol Aging 27:459-70. 2006
    ..Our observations in aged rats suggest that GDNF may be especially effective in reducing obesity in aged obese rats...
  36. ncbi request reprint Circumventing central leptin resistance: lessons from central leptin and POMC gene delivery
    Yi Zhang
    Geriatric Research, Education and Clinical Center, Department of Veterans Affairs Medical Center, Gainesville, FL 32608 1197, USA
    Peptides 27:350-64. 2006
    ..This success highlights the central melanocortin system as a useful drug target for combating obesity...

Research Grants14

  1. Leptin resistance: 1 mechanism underlying age-related obesity
    PHILIP SCARPACE; Fiscal Year: 2007
    ..Such discoveries may lead to new treatments for obesity and the diabetes associated with obesity. ..
  2. Age-related Obesity: Interventions with Gene Delivery
    PHILIP SCARPACE; Fiscal Year: 2006
    ..Such discoveries may lead to new treatments for obesity and the diabetes associated with obesity. ..
  3. IMPAIRED LEPTIN RESPONSIVENESS WITH AGE
    PHILIP SCARPACE; Fiscal Year: 2002
    ..The potential for vitamin A supplementation to reverse the age-related increase in serum leptin and restore leptin responsiveness is addressed in this proposal. ..