Deficits in E2-dependent control of feeding, weight gain, and cholecystokinin satiation in ER-alpha null mice.

Abstract:

:To test the role of gene expression of the classical ER (ER alpha) in the inhibitory effects of E on food intake and body weight, we ovariectomized and administered E2 benzoate (75 pg/d) or vehicle to wild-type (WT) mice and mice with a null mutation of ER alpha (alpha ERKO). Mice were ovariectomized at age 9 wk, at which time there was no significant effect of genotype on food intake or body weight. During an 18-d test after recovery from ovariectomy, vehicle-treated WT mice increased daily food intake and gained more body weight than E2-treated WT mice, whereas food intake and body weight gain were not different in E2- and vehicle-treated alpha ERKO mice. Carcass analysis revealed parallel changes in body lipid content, but not water or protein content. Because an increase in the potency of the peripheral cholecystokinin (CCK) satiation-signaling system mediates part of E2's influence on feeding in rats, the influence of ip injections of 250 microg of the selective CCK(A) receptor antagonist devazepide was then tested. Devazepide increased 3-h food intake in E2-treated WT mice, but was ineffective in both groups of alpha ERKO mice. Furthermore, ip injections of 4 microg/kg CCK-8 increased the number of cells expressing c-Fos immunoreactivity in the nuclei of the solitary tract of E2-treated WT mice more than it did in vehicle-treated WT mice, whereas E2 had no such effect in alpha ERKO mice. Thus, ER alpha is necessary for normal responsivity of food intake, body weight, adiposity, and the peripheral CCK satiation-signaling system to E2 in mice, and ER beta is not sufficient for any of these effects. This is the first demonstration that ER alpha gene expression is involved in the estrogenic control of feeding behavior and weight regulation of female mice.

journal_name

Endocrinology

journal_title

Endocrinology

authors

Geary N,Asarian L,Korach KS,Pfaff DW,Ogawa S

doi

10.1210/endo.142.11.8504

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

4751-7

issue

11

eissn

0013-7227

issn

1945-7170

journal_volume

142

pub_type

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