Impaired leptin responsiveness in aged rats

被引:131
作者
Scarpace, PJ [1 ]
Matheny, M
Moore, RL
Tümer, N
机构
[1] Dept Vet Affairs Med Ctr, Geriatr Res Educ & Clin Ctr 182, Gainesville, FL 32608 USA
[2] Univ Florida, Coll Med, Dept Pharmacol & Therapeut, Gainesville, FL 32610 USA
关键词
D O I
10.2337/diabetes.49.3.431
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
We previously reported that adiposity and serum leptin levels increase with age in male F-344 x BN 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.
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页码:431 / 435
页数:5
相关论文
共 24 条
  • [1] EFFECTS OF INTRACEREBROVENTRICULAR INJECTION OF NEUROPEPTIDE-Y ON ENERGY-METABOLISM
    BILLINGTON, CJ
    BRIGGS, JE
    GRACE, M
    LEVINE, AS
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1991, 260 (02): : R321 - R327
  • [2] Identification of SOCS-3 as a potential mediator of central leptin resistance
    Bjorbaek, C
    Elmquist, JK
    Frantz, JD
    Shoelson, SE
    Flier, JS
    [J]. MOLECULAR CELL, 1998, 1 (04) : 619 - 625
  • [3] RECOMBINANT MOUSE OB PROTEIN - EVIDENCE FOR A PERIPHERAL SIGNAL LINKING ADIPOSITY AND CENTRAL NEURAL NETWORKS
    CAMPFIELD, LA
    SMITH, FJ
    GUISEZ, Y
    DEVOS, R
    BURN, P
    [J]. SCIENCE, 1995, 269 (5223) : 546 - 549
  • [4] Decreased cerebrospinal-fluid/serum leptin ratio in obesity: A possible mechanism for leptin resistance
    Caro, JF
    Kolaczynski, JW
    Nyce, MR
    Ohannesian, JP
    Opentanova, I
    Goldman, WH
    Lynn, RB
    Zhang, PL
    Sinha, MK
    Considine, RV
    [J]. LANCET, 1996, 348 (9021) : 159 - 161
  • [5] SINGLE-STEP METHOD OF RNA ISOLATION BY ACID GUANIDINIUM THIOCYANATE PHENOL CHLOROFORM EXTRACTION
    CHOMCZYNSKI, P
    SACCHI, N
    [J]. ANALYTICAL BIOCHEMISTRY, 1987, 162 (01) : 156 - 159
  • [6] CONDSIDINE RV, 1996, NEW ENGL J MED, V334, P292
  • [7] WEIGHT-REDUCING EFFECTS OF THE PLASMA-PROTEIN ENCODED BY THE OBESE GENE
    HALAAS, JL
    GAJIWALA, KS
    MAFFEI, M
    COHEN, SL
    CHAIT, BT
    RABINOWITZ, D
    LALLONE, RL
    BURLEY, SK
    FRIEDMAN, JM
    [J]. SCIENCE, 1995, 269 (5223) : 543 - 546
  • [8] Physiological response to long-term peripheral and central leptin infusion in lean and obese mice
    Halaas, JL
    Boozer, C
    BlairWest, J
    Fidahusein, N
    Denton, DA
    Friedman, JM
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1997, 94 (16) : 8878 - 8883
  • [9] INVOLVEMENT OF SYMPATHETIC NERVOUS-SYSTEM AND BROWN FAT IN ENDOTOXIN-INDUCED FEVER IN RATS
    JEPSON, MM
    MILLWARD, DJ
    ROTHWELL, NJ
    STOCK, MJ
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY, 1988, 255 (05): : E617 - E620
  • [10] NEUROPEPTIDE-Y - A POTENT INDUCER OF CONSUMMATORY BEHAVIOR IN RATS
    LEVINE, AS
    MORLEY, JE
    [J]. PEPTIDES, 1984, 5 (06) : 1025 - 1029