Comparative Amino Acid and Protein Metabolism in Obese and Non-Obese Zucker Rats

Description of the recessive, homozygote obese Zucker rat (fafa) includes disorders of growth and reproduction. The aim of this study was to compare responsiveness of adenohypophyseal cells, obtained from male fafa rats and from their lean siblings, to growth hormone-releasing factor (GRF) and to luteinizing hormone-releasing hormone (LHRH). Pituitary cells were cultured for 4 days and were then challenged with either GRF-29 (the NH2-terminal 29 amino acid GRF peptide that expresses full biological activity of its parent 44 amino acid molecule) or [D-Trp6]LHRH (LHRH-A, an LHRH agonist). Medium was assayed for growth hormone (GH), luteinizing hormone (LH), and follicle-stimulating hormone (FSH) by radioimmunoassay. Dose-response curves were compared using the computer program ALLFIT. The median effective GRF-29 concentration (EC50) computed for hypophyseal cells cultured from lean animals (0.30 +/- 0.01 fM; means +/- SE of 4 experiments) was less (P less than 0.01) than that calculated for cells obtained from fafa rats (15.8 +/- 6.7 fM). In contrast, cells derived from lean littermates required a larger (EC50) concentration of LHRH-A than did gonadotrophs cultured from obese rats [58.2 +/- 1.2 vs. 10.7 +/- 1.2 pM (P less than 0.01) and 59.4 +/- 10.4 vs. 15.7 +/- 7.6 pM (P less than 0.05)] to secrete LH and FSH, respectively. Our data describe an attenuated pituitary response to GRF-29 and an enhanced response to LHRH-A in the fafa.

Download Full-text

Brain serotonergic activity and plasma amino acid levels in genetically obese Zucker rats

Pharmacology Biochemistry and Behavior ◽

10.1016/0091-3057(82)90476-2 ◽

1982 ◽

Vol 17 (5) ◽

pp. 939-944 ◽

Cited By ~ 19

Author(s):

Judith A. Finkelstein ◽

William T. Chance ◽

Josef E. Fischer

Keyword(s):

Amino Acid ◽

Plasma Amino Acid ◽

Zucker Rats ◽

Serotonergic Activity ◽

Obese Zucker Rats ◽

Amino Acid Levels

Download Full-text

Enhanced N-system activity for neutral amino acid transport in plasma membrane vesicles from livers of genetically obese Zucker rats

Biochemical Society Transactions ◽

10.1042/bst0181249 ◽

1990 ◽

Vol 18 (6) ◽

pp. 1249-1249

Author(s):

BONAVENTURA RUIZ ◽

ANTONIO FELIPE ◽

JAVIER CASADO ◽

MARÇAL PASTOR-ANGLADA

Keyword(s):

Plasma Membrane ◽

Amino Acid ◽

Amino Acid Transport ◽

Membrane Vesicles ◽

Neutral Amino Acid ◽

Zucker Rats ◽

Acid Transport ◽

Plasma Membrane Vesicles ◽

System Activity ◽

Obese Zucker Rats

Download Full-text

Individual amino acid balances in young lean and obese Zucker rats fed a cafeteria diet

Molecular and Cellular Biochemistry ◽

10.1007/bf00928699 ◽

1993 ◽

Vol 121 (1) ◽

pp. 45-57 ◽

Cited By ~ 13

Author(s):

I. Rafecas ◽

M. Esteve ◽

J. A. Fern�ndez-L�pez ◽

X. Remesar ◽

M. Alemany

Keyword(s):

Amino Acid ◽

Cafeteria Diet ◽

Zucker Rats ◽

Individual Amino Acid ◽

Obese Zucker Rats

Download Full-text

Effects of starvation and obesity on somatostatin, insulin, and glucagon release from an isolated perfused organ system

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.241.3.e215 ◽

1981 ◽

Vol 241 (3) ◽

pp. E215-E220 ◽

Cited By ~ 1

Author(s):

G. Boden ◽

C. A. Baile ◽

C. L. McLaughlin ◽

F. M. Matschinsky

Keyword(s):

Amino Acids ◽

Amino Acid ◽

Insulin Release ◽

Glucagon Secretion ◽

Organ System ◽

Zucker Rats ◽

Glucagon Release ◽

Obese Rats ◽

Obese Zucker Rats

We have studied the effects of starvation and of obesity on somatostatin, insulin, and glucagon release from an isolated perfused organ system in fed and 3- and 5-day fasted Holtzman rats and in obese (fa/fa) and lean (Fa/?) Zucker rats. Fasting for 3 days significantly decreased basal (-71%) and amino acid-stimulated (-62%) somatostatin output. After 5 days of starvation, there was a significant increase over the 3-day level in somatostatin output stimulated by amino acid plus glucose (+540%) and by amino acids plus tolbutamide (+238%). Three and five days of starvation severely depressed insulin output while having no statistically significant effects on glucagon secretion. Somatostatin output from obese Zucker rats was significantly greater than that from lean controls in response to amino acids (41.2 +/- 13.2 vs. 16.3 +/- 10.3 ng/25 min, P less than 0.05). Insulin output was greatly increased from obese compared to lean Zucker rats, whereas there were no statistically significant differences in glucagon output. These data show that fasting decreases and obesity increases both somatostatin and insulin release. They suggest that altered stimulation by nutrients was primarily responsible for changes in somatostatin and insulin release observed in starving and obese rats.

Download Full-text

Amino acid uptake by liver of genetically obese Zucker rats

Biochemical Journal ◽

10.1042/bj2800367 ◽

1991 ◽

Vol 280 (2) ◽

pp. 367-372 ◽

Cited By ~ 10

Author(s):

B Ruiz ◽

A Felipe ◽

J Casado ◽

M Pastor-Anglada

Keyword(s):

Plasma Membrane ◽

Amino Acid ◽

Membrane Vesicles ◽

Amino Acid Uptake ◽

Zucker Rats ◽

Acid Uptake ◽

Plasma Membrane Vesicles ◽

Net Uptake ◽

Obese Zucker Rats

Alanine and glutamine uptake by the liver of 50-52-day-old genetically obese Zucker rats and their lean littermates has been studied. The net uptake in vivo of L-alanine is 2-fold higher in the obese animals. No significant change in L-glutamine net balance was found. We also studied the Na(+)-dependent uptake of L-alanine and L-glutamine into plasma-membrane vesicles isolated from either obese- or lean-rat livers. Vmax. values of both L-alanine and L-glutamine transport were 2-fold higher in those preparations from obese rats. No change in Km was observed. As suggested by inhibition studies, this seemed to be mediated by an enhancement of the activities of systems A, ASC and N. We conclude that the liver of the obese Zucker rat is extremely efficient in taking up neutral amino acids from the afferent blood, which results in an enhanced net uptake of L-alanine in vivo. The changes in transport activities at the plasma-membrane level might contribute to increase amino acid disposal by liver, probably for lipogenic purposes, as recently reported by Terrettaz & Jeanrenaud [Biochem. J. (1990) 270, 803-807].

Download Full-text

Effect of exercise and obesity on skeletal muscle amino acid uptake

Journal of Applied Physiology ◽

10.1152/jappl.1990.69.4.1347 ◽

1990 ◽

Vol 69 (4) ◽

pp. 1347-1352 ◽

Cited By ~ 7

Author(s):

J. E. Friedman ◽

P. W. Lemon ◽

J. A. Finkelstein

Keyword(s):

Skeletal Muscle ◽

Amino Acid ◽

Extracellular Fluid ◽

Amino Acid Uptake ◽

Zucker Rats ◽

Acid Uptake ◽

Bicarbonate Buffer ◽

Obese Rats ◽

Obese Zucker Rats

The genetically obese Zucker rat has a reduced capacity to deposit dietary protein in skeletal muscle. To determine whether amino acid uptake by muscle of obese Zucker rats is impaired, soleus strip (SOL) and epitrochlearis (EPI) muscles from 10-wk-old lean and obese Zucker rats were studied in vitro by use of [14C]alpha-aminoisobutyric acid (AIB). Muscles from fasted rats were incubated under basal conditions at rest or after a 1-h treadmill run at 8% grade. To equate total work completed, lean and obese rats ran at 27 and 20 m/min, respectively. Muscles were pinned at resting length, preincubated for 30 min at 37 degrees C in Krebs-Ringer bicarbonate buffer containing 5 mM glucose under 95% O2-5% CO2, and then incubated up to 3 h in Krebs-Ringer bicarbonate with 0.5 mM AIB, [14C]AIB, and [3H]inulin as a marker of extracellular fluid. Basal AIB uptake in EPI and SOL from obese rats was significantly reduced by 40 and 30% (P less than 0.01), respectively, compared with lean rats. For both lean and obese rats, exercise increased (P less than 0.05) basal AIB uptake in EPI and SOL, but the relative increases were greater in the obese rats (EPI 54% and SOL 71% vs. EPI 32% and SOL 37%). These results demonstrate that genetically obese Zucker rats have reduced basal skeletal muscle amino acid uptake and suggest that physical inactivity may partially contribute to this defect.

Download Full-text