Type II glucocorticoid receptors in the CNS regulate metabolism in ob/ob mice independent of protein synthesis

1994 ◽  
Vol 266 (3) ◽  
pp. E427-E432
Author(s):  
H. L. Chen ◽  
D. R. Romsos
Keyword(s):  
Protein Synthesis ◽  
Glucocorticoid Receptors ◽  
Type I ◽  
Intracerebroventricular Injection ◽  
Type Ii ◽  
Ru 486 ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis ◽  
Cerebral Protein Synthesis ◽  
Corticoid Receptor

A single intracerebroventricular injection of dexamethasone rapidly (within 30 min) decreases brown adipose tissue thermogenesis by 25% as assessed by GDP binding and increases plasma insulin twofold in adrenalectomized ob/ob mice. The present study investigated the type of corticoid receptor(s) that mediate these effects and determined whether protein synthesis was necessary for expression of these glucocorticoid actions in ob/ob mice. Intracerebroventricular injection of aldosterone (a type I-corticoid receptor agonist) was ineffective in altering peripheral metabolism in adrenalectomized ob/ob mice, whereas RU-486 (a type II-corticoid receptor antagonist) abolished the effects of dexamethasone. Thus type II-like corticoid receptors, not type I receptors, mediated the rapid effects of dexamethasone in adrenalectomized ob/ob mice. Anisomycin (0.5 mg) administered subcutaneously almost completely suppressed (-92%) cerebral protein synthesis, but anisomycin did not abolish the rapid effects of dexamethasone in adrenalectomized ob/ob mice. Thus protein synthesis is not a prerequisite for rapid effects of dexamethasone in adrenalectomized ob/ob mice.

Glucocorticoid receptors in PVN: interactions with NE, NPY, and Gal in relation to feeding

1993 ◽  
Vol 265 (5) ◽  
pp. E794-E800 ◽  
Author(s):  
D. L. Tempel ◽  
S. F. Leibowitz
Keyword(s):  
Glucocorticoid Receptors ◽  
Steroid Receptors ◽  
Carbohydrate Intake ◽  
Type I ◽  
Fat Intake ◽  
Type Ii ◽  
Stimulatory Action ◽  
Carbohydrate Ingestion ◽  
Ru 486 ◽  
Ru 28318

Norepinephrine (NE) and neuropeptide Y (NPY) potentiate carbohydrate ingestion after injection into the paraventricular nucleus (PVN), whereas injection of galanin (Gal) potentiates fat intake. The present study examines the relation between these neurochemically induced feeding behaviors and the adrenal steroids acting locally within the PVN. Results demonstrate that PVN NE- and NPY-induced carbohydrate intake is abolished by adrenalectomy surgery (ADX) and by local PVN implants of the type II receptor antagonist RU-486. Carbohydrate intake in response to PVN NE or NPY injection is unaffected by the type I antagonist RU-28318. In contrast, the stimulatory effect of PVN Gal injection on fat intake is unchanged by surgical ADX or by PVN administration of RU-486 or RU-28318, suggesting that the stimulatory action of Gal on fat ingestion occurs independently of corticosterone (Cort) and of PVN type I or type II steroid receptors. It is concluded that endogenous Cort has a permissive effect on the carbohydrate feeding responses elicited by NE and NPY in the PVN and that this interaction is mediated by type II glucocorticoid receptors within this nucleus.

Central stimulatory effect of leptin on T3production is mediated by brown adipose tissue type II deiodinase

2002 ◽  
Vol 283 (5) ◽  
pp. E980-E987 ◽  
Author(s):  
Philippe Cettour-Rose ◽  
Albert G. Burger ◽  
Christoph A. Meier ◽  
Theo J. Visser ◽  
Françoise Rohner-Jeanrenaud
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Mrna Expression ◽  
Uncoupling Protein ◽  
Tissue Type ◽  
Type I ◽  
Type Ii ◽  
Brown Adipose ◽  
Small Doses ◽  
Food Consumed

To assess whether intracerebroventricular leptin administration affects monodeiodinase type II (D2) activity in the tissues where it is expressed [cerebral cortex, hypothalamus, pituitary, and brown adipose tissue (BAT)], hepatic monodeiodinase type I (D1) activity was inhibited with propylthiouracil (PTU), and small doses of thyroxine (T4; 0.6 nmol · 100 g body wt−1 · day−1) were supplemented to compensate for the PTU-induced hypothyroidism. Two groups of rats were infused with leptin for 6 days, one of them being additionally treated with reverse triiodothyronine (rT3), an inhibitor of D2. Control rats were infused with vehicle and pair-fed the amount of food consumed by leptin-infused animals. Central leptin administration produced marked increases in D2 mRNA expression and activity in BAT, changes that were likely responsible for increased plasma T3 and decreased plasma T4 levels. Indeed, plasma T3 and T4 concentrations were unaltered by central leptin administration in the presence of rT3. The additional observation of a leptin-induced increased mRNA expression of BAT uncoupling protein-1 suggested that the effect on BAT D2 may be mediated by the sympathetic nervous system.

Postnatal changes in lambs of two pathways for thyroxine 5'-monodeiodination in brown adipose tissue

1991 ◽  
Vol 261 (2) ◽  
pp. E257-E261
Author(s):  
S. Y. Wu ◽  
J. K. Kim ◽  
I. J. Chopra ◽  
Y. Murata ◽  
D. A. Fisher
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Maximum Velocity ◽  
The Other ◽  
Type I ◽  
Type Ii ◽  
Brown Adipose ◽  
Near Term ◽  
Ovine Fetal ◽  
Thermogenic Capacity

We have recently shown that ovine fetal brown adipose tissue (BAT) contains two distinct iodothyronine 5'-monodeiodinase (5'MDI) activities, one with a high Km (type I) and another with a low Km (type II). Both activities increased to maximum levels near term (150 days gestation). BAT plays a major role in neonatal temperature regulation in lambs, and available evidence suggests that BAT 5'MDI activity is closely linked to thermogenic capacity. To better characterize the changes in 5'MDI after birth, we studied both type I and type II 5'MDI in lamb BAT from the time of birth to 30 days of postnatal age. Type I 5'MDI activity [pmol 3,5,3'-triiodothyronine (T3).mg protein-1.h-1] showed no significant changes during the first 11 days after birth [newborn (NB), 95 +/- 16; 1 day, 83 +/- 20; 3-4 days, 80 +/- 11; 10-11 days, 92 +/- 28]. Activity decreased significantly at 30 days (24 +/- 8.9, P less than 0.05). On the other hand, the type II 5'MDI activity (fmol I- released.mg protein-1.h-1) increased significantly (P less than 0.01) during the first 4 days, (NB, 348 +/- 23; 1 day, 679 +/- 37; 3-4 days, 785 +/- 199), decreased toward NB values (401 +/- 87) at 10-11 days of age, and fell to 66 +/- 31 at 30 days (P less than 0.05 vs. NB). Kinetic analysis of BAT type II thyroxine 5'MDI revealed a rise in maximum velocity from NB to 1 and 3-4 days of age without a change in the enzymatic activity Km.(ABSTRACT TRUNCATED AT 250 WORDS)

Mifepristone (RU 486), a blocker of type II glucocorticoid and progestin receptors, reverses a dietary form of obesity

1992 ◽  
Vol 262 (6) ◽  
pp. R1106-R1110 ◽  
Author(s):  
S. Okada ◽  
D. A. York ◽  
G. A. Bray
Keyword(s):  
Body Weight ◽  
Glucocorticoid Receptors ◽  
Body Weight Gain ◽  
The Body ◽  
Receptor Activity ◽  
Minor Role ◽  
Type Ii ◽  
Fat Pad ◽  
Ru 486 ◽  
A Minor

The effect of mifepristone (RU 486), a blocker of type II glucocorticoid receptors on the development of obesity that follows the feeding of a high-fat (HF) diet to Osborne-Mendel (OM) rats, has been investigated. OM rats fed a HF diet gained more weight and had larger retroperitoneal and parametrial fat pads than OM rats fed a high-carbohydrate low-fat (LF) diet. RU 486 (30 mg.kg-1.day-1) for 14 days completely reversed the body weight gain and the increase in fat pad size of OM rats fed a HF diet. RU 486 had no effect on body weight of OM rats fed a LF diet, but did reduce fat pad weights. The data suggest that type II glucocorticoid receptor activity modulates body fat deposition and is essential for the development of obesity, although a minor role for progestin receptor activity cannot be ruled out.

Importance of brain IL-1 type II receptors in fever and thermogenesis in the rat

1993 ◽  
Vol 265 (4) ◽  
pp. E585-E591 ◽  
Author(s):  
G. Luheshi ◽  
S. J. Hopkins ◽  
R. A. Lefeuvre ◽  
M. J. Dascombe ◽  
P. Ghiara ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Low Dose ◽  
Interleukin 1 ◽  
Type I ◽  
Intracerebroventricular Injection ◽  
Type Ii ◽  
Central Effects ◽  
Conscious Rats ◽  
Central Actions ◽  
The Brain

Interleukin-1 (IL-1) acts centrally to induce fever and thermogenesis in rodents. The central actions of IL-1 alpha and IL-1 beta apparently involve different mechanisms, and the effects of IL-1 beta are not consistent with interaction with a type I (IL-1RI) 80-kDa receptor. In the present study the involvement of the type II IL-1 receptor (IL-1RII) was tested in the rat by examining the effects of central injection of a monoclonal antibody (ALVA-42), which blocks the IL-1RII. Pretreatment of rats with ALVA-42 (6 micrograms icv) inhibited the thermogenic and pyrogenic responses to intracerebroventricular injection of 5 ng (but not 50 ng) of IL-1 beta in conscious rats but did not significantly modify responses to IL-1 alpha. ALVA-42 also failed to modify the responses to peripherally administered IL-1 beta (1 microgram) but significantly attenuated the pyrogenic and thermogenic responses to peripheral (125 micrograms) or central (1 microgram) injection of endotoxin. These data indicate that IL-1RII mediates the central effects of a low dose of IL-1 beta, but not IL-1 alpha, on fever and thermogenesis in the rat. They also imply that responses to endotoxin are due, at least in part, to the activation of IL-1RII by IL-1 beta released within the brain and that effects of peripherally injected IL-1 beta involve different mechanisms, probably associated with IL-1RI.

scholarly journals Mitochondria Isolated from Rat Brown Adipose Tissue and Liver

1958 ◽  
Vol 4 (3) ◽  
pp. 287-290 ◽  
Author(s):  
J. D. Lever ◽  
J. B. Chappell
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Liver Mitochondria ◽  
Type I ◽  
Type Ii ◽  
Numerous Type ◽  
Mitochondrial Fractions ◽  
Brown Adipose ◽  
Cytoplasmic Structures ◽  
Brown Fat Mitochondria

Mitochondrial fractions, relatively free from contamination by other cytoplasmic structures, have been isolated by differential centrifugation from homogenates of brown adipose tissue from starved rats. It was possible in such fractions to distinguish two types of mitochondria in this tissue. Type I mitochondria, when morphologically intact, are limited by a bilaminar membrane and show regular parallel cristae. In isolated fractions, a proportion of these mitochondria are swollen, vacuolation occurring within the cristae between their limiting membranes. Type II mitochondria are distinguished from the more numerous type I bodies by the opaque appearance of their matrix. They are limited by a membrane which is in part single, and in part double. They show a few, but crisply outlined internal membranes. Vacuolation of this type of mitochondrion has not been observed. Vacuolation comparable to that in brown fat mitochondria was also observed between the two laminae of the enclosing membrane and within the cristae of liver mitochondria.

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