Estradiol‐Induced Anorexia Is Independent of Leptin and Melanin‐Concentrating Hormone

Wiley - Tập 12 Số 4 - Trang 716-724 - 2004
Nicholas A. Tritos1, Gabriella Segal‐Lieberman2, Peter S. Vezeridis2, Eleftheria Maratos‐Flier2,3
1Joslin Diabetes Center Boston, Massachusetts 02215, USA
2Joslin Diabetes Center, Boston, Massachusetts
3Program in Neuroscience, Harvard Medical School, Boston, Massachusetts

Tóm tắt

Abstract

Objective: Treatment of male rodents with estradiol (E2) is associated with anorexia and weight loss by poorly understood mechanisms. We examined the role of the orexigenic hypothalamic peptide melanin‐concentrating hormone (MCH) and the appetite‐inhibiting, fat‐derived hormone leptin in mediating E2‐induced anorexia.

Research Methods and Procedures: We studied the effect of E2 treatment (implantation of either E2 pellet or matching placebo) in male C57Bl/6J mice, as well as in a lean mouse model (MCH knockout mice) and an obese model (leptin‐deficient ob/ob mice). We also studied the effect of E2 treatment in the context of high‐fat diet.

Results: We confirmed E2 dose‐dependent anorexia in male wild type mice fed a normal chow diet. E2 treatment was associated with a significant decrease in body fat, serum leptin levels, and arcuate hypothalamic proopiomelanocortin expression. E2‐implanted mice also showed increased hypothalamic neuropeptide Y and MCH expression. As MCH has been implicated in E2‐induced hypophagia, we performed E2 pellet implantation in MCH knockout mice and observed hypophagia and weight loss, indicating that MCH is not an essential mediator of E2‐induced anorexia. E2‐implanted ob/ob mice also had hypophagia and weight loss, indicating that leptin is not essential for E2‐induced anorexia. High‐fat diet significantly exacerbated the effect of E2 treatment, leading to a 99.6% decrease in food intake at 48 hours and a 30% loss of body weight within 1 week.

Discussion: The anorectic effects of E2 were independent of MCH and leptin. Our results suggested that E2 may have effects on nutrient preferences.

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Tài liệu tham khảo

10.1016/S0092-8674(00)80937-X

10.1038/35007534

10.1016/0031-9384(72)90340-X

10.1006/appe.2000.0362

10.1126/science.6941477

10.1210/endo-115-1-167

10.1016/0031-9384(79)90028-3

10.1111/j.1749-6632.1986.tb28029.x

10.1016/S0149-7634(05)80183-6

10.1073/pnas.97.23.12729

10.1006/bbrc.2000.3827

10.1210/en.142.11.4751

10.1073/pnas.97.23.12735

10.1016/S0960-0760(01)00136-4

10.1016/0031-9384(94)90134-1

10.1016/S0031-9384(01)00411-5

10.1016/S0196-9781(99)00024-8

10.1677/joe.0.1710349

10.1038/sj.ijo.0801806

10.1016/0031-9384(86)90404-X

10.1037/0735-7044.110.4.823

Dagnault A., 1997, Involvement of the medial preoptic area in the anorectic action of estrogens, Am J Physiol., 272, R311

10.1210/er.20.1.68

10.1210/endo.130.6.1597158

10.1172/JCI118891

Corp E. S., 1990, Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors, Am J Physiol., 259, R317

10.2337/diabetes.47.11.1687

Sahu A., 1998, Leptin decreases food intake induced by melanin‐concentrating hormone (MCH), galanin (GAL) and neuropeptide Y (NPY) in the rat, Endocrinology., 139, 4739, 10.1210/endo.139.11.6432

10.1038/380243a0

10.1038/25341

10.1016/S0006-8993(01)02066-2

10.1054/npep.1999.0055

Bonavera J. J., 1994, Anorectic effects of estrogen may be mediated by decreased neuropeptide‐Y release in the hypothalamic paraventricular nucleus, Endocrinology., 134, 2367, 10.1210/endo.134.6.8194462

Mystkowski P., 2000, Hypothalamic melanin‐concentrating hormone and estrogen‐induced weight loss, J Neurosci., 20, 8637, 10.1523/JNEUROSCI.20-22-08637.2000

Inoue S., 1977, Comparison of metabolic alterations in hypothalamic and high fat diet‐induced obesity, Am J Physiol., 233, R162

10.1038/nm1295-1311

Salmon D. M., 1985, Effect of dietary fat content on the incidence of obesity among ad libitum fed mice, Int J Obes Relat Metab Disord., 9, 443

10.1002/(SICI)1096-9861(19981228)402:4<442::AID-CNE2>3.0.CO;2-R

10.1016/0006-8993(89)90062-0

10.1016/0006-8993(92)90694-5

10.1152/ajpendo.1994.267.1.E32

10.1016/S0092-8674(00)81973-X

10.1677/joe.0.160R007

10.1073/pnas.96.19.10911

10.1016/S0092-8674(00)81965-0

10.1046/j.1460-9568.2000.00919.x

10.1126/science.288.5475.2379

10.2337/diabetes.51.2.271

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Wiley

Tập 12 Số 4

716-724

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