Glucocorticoids in the CNS regulate BAT metabolism and plasma insulin in ob/ob mice

Walker, Hetty; Romsos, Dale R.

doi:10.1152/ajpendo.1992.262.1.e110

Cited by 17 publications

(19 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Of note is the observation that Y2 receptor deficiency also reduced the responsiveness of mice to exogenous corticosterone administration. In wild-type mice, corticosterone administration resulted in an obesity syndrome, which has been observed by other investigations of rats (6) and mice (38). This finding may be related to the fact that glucocorticoids are known to increase NPY mRNA and͞or peptide levels and Y receptor expression in the hypothalamus in vivo (6,39) and in vitro (39).…”

Section: Discussionsupporting

confidence: 68%

Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice

Sainsbury

Schwarzer

Couzens

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

224

204

View full text Add to dashboard Cite

Neuropeptide Y is implicated in energy homeostasis, and contributes to obesity when hypothalamic levels remain chronically elevated. To investigate the specific role of hypothalamic Y2 receptors in this process, we used a conditional Y2 knockout model, using the Cre-lox system and adenoviral delivery of Cre-recombinase. Hypothalamus-specific Y2-deleted mice showed a significant decrease in body weight and a significant increase in food intake that was associated with increased mRNA levels for the orexigenic NPY and AgRP, as well as the anorexic proopiomelanocortin (POMC) and cocaine-and amphetamine-regulated transcript (CART) in the arcuate nucleus. These hypothalamic changes persisted until at least 34 days after Y2 deletion, yet the effect on body weight and food intake subsided within this time. Plasma concentrations of pancreatic polypeptide and corticosterone were 3-to 5-fold increased in hypothalamus-specific Y2 knockout mice. Germ-line Y2 receptor knockout also produced a significant increase in plasma levels of pancreatic polypeptide. However, these mice differed from conditional knockout mice in that they showed a sustained reduction in body weight and adiposity associated with increased NPY and AgRP but decreased POMC and CART mRNA levels in the arcuate nucleus. The transience of the observed effects on food intake and body weight in the hypothalamus-specific Y2 knockout mice, and the difference of this model from germ-line Y2 knockout mice, underline the importance of conditional models of gene deletion, because developmental, secondary, or extrahypothalamic mechanisms may mask such effects in germ-line knockouts.neuropeptide Y ͉ pancreatic polypeptide ͉ cre-lox ͉ arcuate nucleus N europeptide Y (NPY) in the hypothalamus is known to be a strong stimulus for food intake (1, 2), and induces many neuroendocrine and metabolic changes that favor energy storage. Such changes include decreased thermogenesis in brown adipose tissue, hyperinsulinemia, hypercorticosteronemia, and insulin hyperresponsiveness in white adipose tissue (3, 4). All of these neuroendocrine and metabolic effects of central NPY administration persist even when NPY-induced hyperphagia is prevented by pair-feeding (3, 4), demonstrating that hyperphagia is not the only mechanism by which central NPY increases adiposity.Although numerous other hormones and peptides act within the hypothalamus to regulate energy homeostasis, many exert an important component of their effects via actions on the hypothalamic NPY-ergic system (5-7), demonstrating the pivotal role of NPY in coordinating energy homeostasis. However, it is not clear which of the 5 cloned Y-receptors (Y1, Y2, Y4, Y5, and y6) are responsible for these effects (8).There is increasing evidence that Y2 receptors are involved in energy homeostasis. Over 80% of NPY-containing neurons in the arcuate nucleus (Arc) coexpress Y2 receptor mRNA (9). This presynaptic Y2 receptor has therefore been proposed to regulate the release of NPY (10, 11) and other colocalized neurotransmitters involved ...

show abstract

Section: Discussionsupporting

confidence: 68%

Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice

Sainsbury

Schwarzer

Couzens

et al. 2002

Proc. Natl. Acad. Sci. U.S.A.

224

204

View full text Add to dashboard Cite

show abstract

“…48 Thus, the failure of RU-486 to fully correct hyperinsulinemia in ob/ob mice may have prevented complete restoration of b 3 -AR expression. Given that adrenalectomy or RU-486 treatment at younger ages is more effective in correcting hyperinsulinemia in obese rodents, 10,11,14,31 it will be interesting to see if a similar experimental approach will fully restore b 3 -AR expression. Recent work has shown that b 3 -AR expression is also modulated by thyroid status.…”

Section: Ru-486 Ameliorates Diabetesmentioning

confidence: 99%

RU-486 (Mifepristone) ameliorates diabetes but does not correct deficient β-adrenergic signalling in adipocytes from mature C57BL/6J-ob/ob mice

et al. 1997

View full text Add to dashboard Cite

OBJECTIVE: To investigate the role of hypercorticism in the development of compromised b-adrenergic signalling in adipocytes of mature C57BL/6J-ob/ob mice. DESIGN AND EXPERIMENTAL UNITS: Mature male ob/ob mice and their lean littermates were treated with vehicle or the speci®c glucocorticoid receptor (GR) antagonist, RU-486 (30 mg/kg bw/d) for 21 d. MEASUREMENTS: Blood glucose, serum insulin, adipocyte Glut-4 expression, adipocyte G s a expression, adenylylcyclase activation by b-adrenergic receptor (b-AR) agonists in adipocyte membranes and mRNA levels for b 1 -, b 2 -and b 3 -adrenergic receptor subtypes in adipocytes. RESULTS: RU-486 reduced blood glucose levels in ob/ob mice to levels that were not different from lean mice. RU-486 also reduced serum insulin by approximately 50% in ob/ob mice, but failed to restore depressed G s a or GLUT-4 expression in adipocytes of ob/ob mice. RU-486 produced a two-fold increase in b 3 -AR mRNA in ob/ob mice and a small but signi®cant improvement in isoprenaline-mediated adenylylcyclase activation. CONCLUSIONS: The present results indicate that glucocorticoid antagonism ameliorates diabetic symptoms of the mature ob/ob mouse, but does not lessen their obesity or fully reverse de®cient expression and function of components of the adipocyte b-adrenergic signalling cascade.

show abstract

“…6 In MSG-treated rats high levels of corticosterone have also been described 7,8 and this is probably related to the central (via sympathetic nervous system) or directly suppresive effect of glucocorticoids on brown adipose tissue (BAT) activity. 9,10 In most types of obese animals, BAT is in a thermogenically quiescent and relatively atrophied state. Recently, reduced GLUT4 in BAT was found in both 30 and 90 day old MSG-treated rats.…”

Section: Introductionmentioning

confidence: 99%

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats

et al. 2001

View full text Add to dashboard Cite

OBJECTIVE:To determine the metabolic alterations that lead to the neonatal administration of monosodium glutamate (MSG), which results in arrested growth and obesity. ANIMALS AND DESIGN: Wistar rats were injected 5 times, every other day, with 4 g of MSGakg b.w. or with hyperosmotic saline (controls), within the ®rst 10 days of life, and were studied at the age of 30 days. RESULTS: Body weight was lower, whereas adipocyte lipid content, cell diameter, surface area and volume were higher in MSG rats than in controls. Plasma glucose, insulin, NEFA, glycerol and triglyceride levels, and in vitro production of NEFA by lumbar fat pad pieces incubated under basal conditions or in the presence of epinephrine and epinephrine plus glucose in the media were lower in MSG than in control rats. In the same fat pad pieces, the conversion of 1-14 C-glycerol into fatty acids was always enhanced and its conversion into glyceride glycerol was enhanced when incubations were carried out in the presence of epinephrine or glucose. Both the hormone sensitive lipase activity and mRNA expression were lower in adipose tissue from MSG rats. Besides, the number of insulin receptors, lipid synthesis from U 14 C glucose, 3 H-2-deoxy D-glucose uptake and cellular GLUT4 translocation index were higher in adipocytes from MSG rats than from the controls. CONCLUSION: It is proposed that an enhanced insulin sensitivity in 1 month old MSG rats is responsible for the decreased lipolytic activity and enhanced glucose uptake. In addition, the enhanced lipogenesis and glycerol reutilization seen in their adipose tissue, disturbs the normal balance between fat depots breakdown and accumulation in favor of the latter.

show abstract

Glucocorticoids in the CNS regulate BAT metabolism and plasma insulin in ob/ob mice

Cited by 17 publications

References 20 publications

Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice

Important role of hypothalamic Y2 receptors in body weight regulation revealed in conditional knockout mice

RU-486 (Mifepristone) ameliorates diabetes but does not correct deficient β-adrenergic signalling in adipocytes from mature C57BL/6J-ob/ob mice

Decreased lipolysis and enhanced glycerol and glucose utilization by adipose tissue prior to development of obesity in monosodium glutamate (MSG) treated-rats

Contact Info

Product

Resources

About