Differential expression of hypothalamic neuropeptides in the early phase of diet-induced obesity in mice

被引:185
作者
Ziotopoulou, M [1 ]
Mantzoros, CS [1 ]
Hileman, SM [1 ]
Flier, JS [1 ]
机构
[1] Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Div Endocrinol, Boston, MA 02215 USA
来源
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM | 2000年 / 279卷 / 04期
关键词
high-fat diet; hypothalamus; leptin;
D O I
10.1152/ajpendo.2000.279.4.E838
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Exposure to high-fat diets for prolonged periods results in positive energy balance and obesity, but little is known about the initial physiological and neuroendocrine response of obesity-susceptible strains to high-fat feeding. To assess responses of C57BL/6J mice to high- and low-fat diets, we quantitated the hypothalamic expression of neuropeptides implicated in weight regulation and neuroendocrine function over a 2-wk period. Exposure to high- fat diet increased food consumption over a 2-day period during which leptin levels were increased when assessed by a frequent sampling protocol [area under the curve (AUC): 134.6 +/- 10.3 vs. 100 +/- 12.3, P = 0.03 during first day and 126.5 +/- 8.2 vs. 100 +/- 5.2, P = 0.02 during second day]. During this period, hypothalamic expression of neuropeptide Y (NPY) and agouti-related protein (AgRP) decreased by similar to 30 and 50%, respectively (P < 0.001). After 1 wk, both caloric intake and hypothalamic expression of NPY and AgRP returned toward baseline. After 2 wk, cumulative caloric intake was again higher in the high- fat group, and now proopiomelanocortin (POMC) was elevated by 76% (P = 0.01). This study demonstrates that high- fat feeding induces hyperphagia, hyperleptinemia, and transient suppression of orexigenic neuropeptides during the first 2 days of diet. The subsequent induction of POMC may be a second defense against obesity. Attempts to understand the hypothalamic response to high- fat feeding must examine the changes as they develop over time.
引用
收藏
页码:E838 / E845
页数:8
相关论文
共 42 条
[1]   Distinct physiologic and neuronal responses to decreased leptin and mild hyperleptinemia [J].
Ahima, RS ;
Kelly, J ;
Elmquist, JK ;
Flier, JS .
ENDOCRINOLOGY, 1999, 140 (11) :4923-4931
[2]   Role of leptin in the neuroendocrine response to fasting [J].
Ahima, RS ;
Prabakaran, D ;
Mantzoros, C ;
Qu, DQ ;
Lowell, B ;
MaratosFlier, E ;
Flier, JS .
NATURE, 1996, 382 (6588) :250-252
[3]   Postnatal leptin surge and regulation of circadian rhythm of leptin by feeding - Implications for energy homeostasis and neuroendocrine function [J].
Ahima, RS ;
Prabakaran, D ;
Flier, JS .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 101 (05) :1020-1027
[4]   Regulation of plasma leptin in mice: Influence of age, high-fat diet, and fasting [J].
Ahren, B ;
Mansson, S ;
Gingerich, RL ;
Havel, PJ .
AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY, 1997, 273 (01) :R113-R120
[5]   MACRONUTRIENT TYPE INDEPENDENTLY OF ENERGY-INTAKE MODULATES HYPOTHALAMIC NEUROPEPTIDE-Y IN LONG-EVANS RATS [J].
BECK, B ;
STRICKERKRONGRAD, A ;
BURLET, A ;
MAX, JP ;
MUSSE, N ;
NICOLAS, JP ;
BURLET, C .
BRAIN RESEARCH BULLETIN, 1994, 34 (02) :85-91
[6]   INFLUENCE OF DIET COMPOSITION ON FOOD-INTAKE AND HYPOTHALAMIC NEUROPEPTIDE-Y (NPY) IN THE RAT [J].
BECK, B ;
STRICKERKRONGRAD, A ;
BURLET, A ;
NICOLAS, JP ;
BURLET, C .
NEUROPEPTIDES, 1990, 17 (04) :197-203
[7]   Resistance to diet-induced obesity is associated with increased proopiomelanocortin mRNA and decreased neuropeptide Y mRNA in the hypothalamus [J].
Bergen, HT ;
Mizuno, T ;
Taylor, J ;
Mobbs, CV .
BRAIN RESEARCH, 1999, 851 (1-2) :198-203
[8]   Identification of SOCS-3 as a potential mediator of central leptin resistance [J].
Bjorbaek, C ;
Elmquist, JK ;
Frantz, JD ;
Shoelson, SE ;
Flier, JS .
MOLECULAR CELL, 1998, 1 (04) :619-625
[9]   RECOMBINANT MOUSE OB PROTEIN - EVIDENCE FOR A PERIPHERAL SIGNAL LINKING ADIPOSITY AND CENTRAL NEURAL NETWORKS [J].
CAMPFIELD, LA ;
SMITH, FJ ;
GUISEZ, Y ;
DEVOS, R ;
BURN, P .
SCIENCE, 1995, 269 (5223) :546-549
[10]   Narcolepsy in orexin knockout mice:: Molecular genetics of sleep regulation [J].
Chemelli, RM ;
Willie, JT ;
Sinton, CM ;
Elmquist, JK ;
Scammell, T ;
Lee, C ;
Richardson, JA ;
Williams, SC ;
Xiong, YM ;
Kisanuki, Y ;
Fitch, TE ;
Nakazato, M ;
Hammer, RE ;
Saper, CB ;
Yanagisawa, M .
CELL, 1999, 98 (04) :437-451