P. J. Scarpace

University of Florida

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Trends

Author Order

Document Type

Co-Authors

Nihal Tümer

University of Florida

Michael E. Matheny

Vanderbilt University

Stephen E. Borst

North Florida/South Georgia Veterans Health System

Isabelle Côté

University of Florida

Hale Z. Toklu

University of Central Florida

Bradley S. Bender

St. George's University

Drake Morgan

University of Florida

R L Moore

Geriatric Research Education and Clinical Center

Yasemin Sakarya

University of Florida

Itamar B. Abrass

University of Washington

Cooperative Institutions

University of Florida

Florida College

Geriatric Research Education and Clinical Center

Malcom Randall VA Medical Center

University of Missouri

North Florida/South Georgia Veterans Health System

Veterans Health Administration

United States Department of Veterans Affairs

University of Kansas Medical Center

University of Missouri Health System

Author Statistics

Papers

Citation

H-Index

i-10 index

Research Field

Uncoupling Proteins 2 and 3 With Age: Regulation by Fasting and 3-Adrenergic Agonist Treatment

The Journals of Gerontology Series A (2000)

P. J. Scarpace M. V. Kumar H. Li Nihal Tümer

In rodents, adaptive thermogenesis in brown adipose tissue (BAT) serves both to regulate body mass after hyperphagia and to conserve energy during food deprivation. In addition to uncoupling protein 1 (UCP1), UCP3 and possibly UCP2 may have a role in energy homeostasis in BAT. We examined basal levels of UCP2 and UCP3 mRNA with age and regulation of UCP1, UCP2, and UCP3 mRNA by two conditions known to modulate energy homeostasis: fasting and β3-adrenergic agonists. UCP1, UCP2, and UCP3 mRNA levels were unchanged between 3, 24, and 31 months of age in BAT, and UCP2 and UCP3 mRNA levels were unchanged between 6 and 24 months of age in retroperitoneal white adipose tissue (RTWAT). Following a 2-day fast, there were sizable reductions in BAT UCP1 and UCP3 mRNA, but these decreases with fasting were significantly less in the older compared with the young rats. Fasting had no effect on UCP2 mRNA levels at any age. The β3-adrenergic agonist, CL316,243, increased BAT UCP1 and UCP3 mRNA equally in both young and old rats. The β3-adrenergic agonist did not increase UCP2 mRNA in BAT but did increase expression in RTWAT of both young and old rats. In summary, these data indicate that the expression of the three uncoupling proteins is unchanged with age. Although the upregulation of these uncoupling proteins by β3-adrenergic agonist treatment is maintained with age, the downregulation by fasting is diminished with age. The parallel regulation of UCP1 and UCP3 expression in BAT suggests that UCP3, like UCP1, may have a role in energy homeostasis in BAT. The diminished downregulation of UCP1 and UCP3 expression in BAT by fasting suggests that energy conservation in response to food deprivation is impaired with age, and this may contribute to an inability of older animals to maintain body mass during periods when food is limited.

Adrenergic agonist

10.1093/gerona/55.12.b588

Cite

Citations (8)

Preparation and immunological characteristics of biologically active radioiodinated human calcitonin. [Rats, /sup 125/I]

P. J. Scarpace L.J. Deftos

Synthetic human calcitonin (hCT) was radioiodinated by electrolysis and chloramine-T oxidation. The electrolytic method was adapted for practicable quantities of hormone and isotope with no loss in efficiency of labeling. The immunological characteristics of the two hormone preparations were nearly identical using four calcitonin antisera with specificities for the regions 17-21, 17-29, 28-29, and 29-32 of hCT, respectively. However, only the electrolytically-labeled preparation retained full ability to produce hypocalcemia in vivo and stimulate cyclic AMP production in kidney homogenates of the rat. In addition, the electrolytically-iodinated hormone remained nearly homogeneous during 104 days of storage and the specific activity as measured by radioimmunoassay remained constant during one half-life of the isotope. These studies demonstrate that electrolytic iodination of hCT results in a tracer which is immunochemically stable and biologically active.

Chloramine-T

Specific activity

Source

Cite

Citations (0)

Differential Modulation of Energy Balance by Leptin, Ciliary Neurotrophic Factor, and Leukemia Inhibitory Factor Gene Delivery: Microarray Deoxyribonucleic Acid-Chip Analysis of Gene Expression

Endocrinology (2004)

Victor Prima Michael Tennant Oleg S. Gorbatyuk Nicholas Muzyczka P. J. Scarpace

Most obese animal models, whether associated with genetic, diet-induced, or age-related obesity, display pronounced leptin resistance, rendering leptin supplement therapy ineffective in treating obesity. Ciliary neurotrophic factor (CNTF) has been recently used to invoke leptin-like signaling pathways, thereby circumventing leptin resistance. In the current study, we characterize immediate and long-term molecular events in the hypothalamus of rats exposed to the sustained ectopic expression of leptin, CNTF, or leukemia inhibitory factor, another neurocytokine of IL-6 family, all delivered centrally via a viral vector. The respective transgene-encoded ligands induced similar but not identical metabolic responses as assessed by the reduction in body weight gain and changes in food intake. To define molecular mechanisms of weight-reducing and anorexigenic action of cytokines, we have analyzed the gene expression profiles of 1300 brain-specific genes in the hypothalami of normal rats subjected to the prolonged cytokine action for 10 wk. We present evidence that constitutive expression of cytokines in the brain induces changes in gene expression characteristic of chronic inflammation leading to either temporal weight reduction (CNTF) or severe cachexia (leukemia inhibitory factor). Our results convey a cautionary note regarding potential use of the tested cytokines in therapeutic applications.

Ciliary neurotrophic factor

10.1210/en.2003-1376

Cite

Citations (40)

Thermogenesis in brown adipose tissue with age: Post-receptor activation by forskolin

Pflügers Archiv - European Journal of Physiology (1996)

Philip J. Scarpace Michael E. Matheny P. J. Scarpace

Thermogenin

Isoprenaline

10.1007/bf02207276

Cite

Citations (32)

Impaired leptin responsiveness in aged rats.

Diabetes (2000)

P. J. Scarpace Michael E. Matheny R L Moore Nihal Tümer

We previously reported that adiposity and serum leptin levels increase with age in male F-344xBN rats and that when physiological levels of serum leptin are manipulated by fasting, there is a corresponding reciprocal change in hypothalamic neuropeptide Y (NPY) mRNA in young rats, but there are no changes in older rats. These findings suggest that the regulation of hypothalamic NPY mRNA by leptin may be impaired with age. To test this hypothesis, we infused saline or leptin for 7 days into ad libitum-fed rats and compared these with saline-infused rats that were pair-fed the amount of food consumed by the leptin-treated rats. We examined daily food consumption, body weight, whole-body oxygen consumption, serum leptin, and NPY mRNA in the hypothalamus. Food consumption decreased by 50% in the leptin-infused compared with the saline-infused young rats but only decreased by 20% in the aged rats. In the leptin-treated young rats, there was a 24% increase in oxygen consumption compared with the pair-fed rats, but there were no changes in oxygen consumption in the aged rats. Leptin infusion diminished hypothalamic NPY levels by nearly 50% compared with pair-fed young rats, whereas there were no changes in the hypothalamic NPY mRNA levels in senescent rats. In summary, aged rats demonstrate a reduced responsiveness to leptin, including a diminished decrease in food intake and no increase in energy expenditure. These diminished responses to leptin were associated with and may be the result of an impaired suppression of hypothalamic NPY mRNA levels. This leptin resistance may be due to either the elevated obesity and serum leptin with age or due to age itself, or both.

10.2337/diabetes.49.3.431

Cite

Citations (156)

Alteration of contractile force and mass in the senescent diaphragm with β₂-agonist treatment

Journal of Applied Physiology (2002)

Wesley N. Smith Amie J. Dirks Takao Sugiura Susan Müller P. J. Scarpace

Aging is associated with a decrease in diaphragmatic maximal tetanic force production (P o ) in senescent rats. Treatment with the β 2 -agonist clenbuterol (CB) has been shown to increase skeletal muscle mass and P o in weak locomotor skeletal muscles from dystrophic rodents. It is unknown whether CB can increase diaphragmatic mass and P o in senescent rats. Therefore, we tested the hypothesis that CB treatment will increase specific P o (i.e., force per cross-sectional area) and mass in the diaphragm of old rats. Young (5 mo) and old (23 mo) male Fischer 344 rats were randomly assigned to one of the following groups ( n = 10/group): 1) young CB treated; 2) young control; 3) old CB treated; and 4) old control. Animals were injected daily with either CB (2 mg/kg) or saline for 28 days. CB increased ( P < 0.05) the mass of the costal diaphragm in both young and old animals. CB treatment increased diaphragmatic-specific P o in old animals (∼15%; P < 0.05) but did not alter ( P > 0.05) diaphragmatic-specific P o in young animals. Biochemical analysis indicated that the improved maximal specific P o in the diaphragm of CB-treated old animals was not due to increased myofibrillar protein concentration. Analysis of the myosin heavy chain (MHC) content of the costal diaphragm revealed a CB-induced increase ( P < 0.05) in type IIb MHC and a decrease in type I, IIa, and IIx MHC in both young and old animals. These data support the hypothesis that CB treatment can restore the age-associated decline in both diaphragmatic-specific P o and muscle mass.

Diaphragm (acoustics)

Myofibril

Diaphragm muscle

10.1152/japplphysiol.00576.2001

Cite

Citations (29)

Adrenergic Signal Transduction in Aging Parotid and Submandibular Salivary Glands

Journal of Gerontology (1991)

Gayathiri Rajakumar P. J. Scarpace

This study assessed agonist-and post-receptor-stimulated adenylate cyclase (AC) activity in parotid and submandibular salivary glands from female F-344 rats of 3,12, and 24 months of age. Isoproterenol-stimulated dose-response activation of adenylate cyclase was unchanged between 3 and 12 months but decreased at 24 months (p p≤ .05). Forskolin-stimulated AC activity, representing catalytic unit activity, was decreased at 24 months in the parotid (p p≤ .05) and at 12 months (p p≤ .05) and 24 months (p p≤ .01) in the submandibular gland,β-adrenergic signal transduction in salivary glands stimulates the secretion of salivary proteins that have important functions in the maintenance of oral health.

10.1093/geronj/46.6.b249

Cite

Citations (9)

Age-Associated Decrease in Beta-Adrenergic Receptors and Adenylate Cyclase Activity in Rat Brown Adipose Tissue

Journal of Gerontology (1988)

P. J. Scarpace A. D. Mooradian J. E. Morley

Journal Article Age-Associated Decrease in Beta-Adrenergic Receptors and Adenylate Cyclase Activity in Rat Brown Adipose Tissue Get access Philip J. Scarpace, Philip J. Scarpace Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Sepulveda, and Department of Medicine, University of CaliforniaLos Angeles Search for other works by this author on: Oxford Academic PubMed Google Scholar Arshag D. Mooradian, Arshag D. Mooradian Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Sepulveda, and Department of Medicine, University of CaliforniaLos Angeles Search for other works by this author on: Oxford Academic PubMed Google Scholar John E. Morley John E. Morley Geriatric Research, Education and Clinical Center, Veterans Administration Medical Center, Sepulveda, and Department of Medicine, University of CaliforniaLos Angeles Search for other works by this author on: Oxford Academic PubMed Google Scholar Journal of Gerontology, Volume 43, Issue 3, May 1988, Pages B65–B70, https://doi.org/10.1093/geronj/43.3.B65 Published: 01 May 1988 Article history Received: 07 November 1986 Accepted: 27 December 1987 Published: 01 May 1988

10.1093/geronj/43.3.b65

Cite

Citations (42)

Activation of the central melanocortin system chronically reduces body mass without the necessity of long-term caloric restriction

Canadian Journal of Physiology and Pharmacology (2016)

Isabelle Côté Yasemin Sakarya Nataliya Kirichenko Drake Morgan C.S. Carter

Melanotan II (MTII) is a potent appetite suppressor that rapidly reduces body mass. Given the rapid loss of anorexic response upon chronic MTII treatment, most investigations have focused on the initial physiological adaptations. However, other evidence supports MTII as a long-term modulator of energy balance that remains to be established. Therefore, we examined the chronic effects of MTII on energy homeostasis. MTII (high or low dose) or artificial cerebrospinal fluid (aCSF) was infused into the lateral ventricle of the brain of 6-month-old F344BN rats (6-7/group) over 40 days. MTII suppressed appetite in a dose-dependent manner (P < 0.05). Although food intake promptly rose back to control level, body mass was persistently reduced in both MTII groups (P < 0.01). At day 40, both MTII groups displayed lower adiposity than the aCSF animals (P < 0.01). These results show that MTII chronically reduces body mass without the requirement of long-term caloric restriction. Our study proposes that food restriction helps initiate mass loss; however, combined with a secondary pharmacological approach preserving a negative energy balance state over time may help combat obesity.

Caloric theory

10.1139/cjpp-2016-0290

Cite

Citations (5)

Differential physiological responses to central leptin overexpression in male and female rats

Journal of Neuroendocrinology (2017)

Isabelle Côté S. M. Green Hale Z. Toklu Drake Morgan C. S. Carter

Brains of females are more sensitive to the acute catabolic actions of leptin. However, sex differences in the long‐term physiological responses to central leptin receptor modulation are unknown. Accordingly, we centrally delivered a viral vector to overexpress leptin (Leptin), a neutral leptin receptor antagonist (Leptin‐Antagonist) or a green fluorescence protein ( GFP ) (Control). We examined chronic changes in body weight and composition in male and female rats. Females displayed greater and sustained responses to Leptin, whereas males rapidly lost physiological effects and developed leptin resistance as confirmed by lower acute leptin‐mediated phosphorylation of signal transducer and activator of transcription 3 (P‐ STAT 3). Surprisingly, despite persistent physiological responses, Leptin‐females also exhibited reduced acute leptin‐mediated P‐ STAT 3, suggesting an onset of leptin resistance near time of death. In line with this interpretation, Leptin‐females and Control‐females consumed the same amount of food on the last day of the experiment. Both Leptin‐Antagonist groups gained similar percentages of their initial body weight and fat mass, whereas only Leptin‐Antagonist‐females gained lean body mass. Consequently, the lean/fat mass ratio with Leptin‐Antagonist was preserved in females and decreased in males, suggesting a deterioration of body composition in males. In summary, the present study establishes that females are more responsive to long‐term central leptin overexpression than males and that leptin antagonism has a greater physiological impact in males. The hormone environment may have played a role in these processes; however, future studies are needed to establish whether such physiological responses are mediated by female or male sex hormones.

Leptin receptor

10.1111/jne.12552

Cite

Citations (13)