Injection of prostaglandin E2 into the anterior hypothalamic preoptic area activates brown adipose tissue thermogenesis in the rat

Amir, Shimon; Schiavetto, Alessandra

doi:10.1016/0006-8993(90)90206-q

Cited by 52 publications

(24 citation statements)

References 28 publications

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“…This effect is inhibited by the cyclooxygenase inhibitors indomethacine and naproxen, and, accordingly, an increased production of prostaglandin E 2 (PGE 2 ) follows TLQP-21 administration. Central induction or treatment with PGE 2 induces hyperthermia and increases EE (33)(34)(35). Therefore, chronic TLQP-21-induced upset of energy balance is compatible with a mechanism of action involving central PGE 2 production.…”

Section: Tlqp-21 Confersmentioning

confidence: 74%

TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity

Bartolomucci

Corte

Possenti

et al. 2006

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

139

200

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The vgf gene has been identified as an energy homeostasis regulator. Vgf encodes a 617-aa precursor protein that is processed to yield an incompletely characterized panel of neuropeptides. Until now, it was an unproved assumption that VGF-derived peptides could regulate metabolism. Here, a VGF peptide designated TLQP-21 was identified in rat brain extracts by means of immunoprecipitation, microcapillary liquid chromatography-tandem MS, and database searching algorithms. Chronic intracerebroventricular (i.c.v.) injection of TLQP-21 (15 g͞day for 14 days) increased resting energy expenditure (EE) and rectal temperature in mice. These effects were paralleled by increased epinephrine and up-regulation of brown adipose tissue ␤2-AR (␤2 adrenergic receptor) and white adipose tissue (WAT) PPAR-␦ (peroxisome proliferator-activated receptor ␦), ␤3-AR, and UCP1 (uncoupling protein 1) mRNAs and were independent of locomotor activity and thyroid hormones. Hypothalamic gene expression of orexigenic and anorexigenic neuropeptides was unchanged. Furthermore, in mice that were fed a high-fat diet for 14 days, TLQP-21 prevented the increase in body and WAT weight as well as hormonal changes that are associated with a high-fat regimen. Biochemical and molecular analyses suggest that TLQP-21 exerts its effects by stimulating autonomic activation of adrenal medulla and adipose tissues. In conclusion, we present here the identification in the CNS of a previously uncharacterized VGF-derived peptide and prove that its chronic i.c.v. infusion effected an increase in EE and limited the early phase of diet-induced obesity.autonomic nervous system ͉ ␤ adrenergic receptor ͉ MALDI-TOF ͉ neuropeptide ͉ peroxisome proliferator-activated receptor ␦ E nergy homeostasis is a complex physiological function that is coordinated at multiple levels. Stimulated by the discovery of leptin and the pandemic diffusion of obesity and type-2 diabetes, the regulation of energy homeostasis has received increasing attention (1-4). New players are being continuously identified and screened as molecular candidates to counteract obesity (5-10). Vgf, initially identified as a nerve growth factor-responsive gene, is also robustly induced by BDNF and neurotrophin 3 and marginally induced by epidermal and fibroblast growth factors, IL-6, and insulin (11-13). Vgf received great attention after the observation that VGF-deficient mice are lean, hypermetabolic, and resistant to various types of obesity (14, 15). In the rat brain, VGF is abundant in the cortex, hypothalamus, hippocampus, and olfactory system and in a number of thalamic, septal, amygdaloid, and brainstem nuclei, with the local availability of neurotrophins for receptor occupation being the critical parameter in determining its selective expression (12, 13). Changes in vgf expression also increase in the arcuate nucleus of fasted rats (14) and hamsters that are exposed to a short or long day's length (16). However, up until now, it was still unproved that VGF-derived peptides are metabolic neuromodulators (...

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Section: Tlqp-21 Confersmentioning

confidence: 74%

TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity

Bartolomucci

Corte

Possenti

et al. 2006

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

139

200

View full text Add to dashboard Cite

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“…Addition of the vehicle (Veh), to be used for benidi- Figure 1 Absence of thermogenic effect of benidipine in isolated brown-fat cells. Isolated brown-fat cells from rats acclimated to 21 C were incubated in KrebsaRinger bicarbonate buffer. In trace A, the cells were ®rst treated with 10 ml 34% ethanol in 0.5% Tween-80 in saline (that is, the vehicle for benidipine) (Veh), and 5 min later, 1 mM noradrenaline (NA) (dissolved in water) was added.…”

Section: Resultsmentioning

confidence: 99%

Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists

et al. 1999

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BACKGROUND: Anti-obesity effects of calcium antagonists such as benidipine and nifedipine have been described in rodent obesity models, but the mode of action of the calcium antagonists as anti-obesity agents has not been established. OBJECTIVE: To examine whether the anti-obesity effects of calcium antagonists (here benidipine) could be ascribed to a direct stimulation of brown adipose tissue (BAT) thermogenesis. METHODS: Examination of the ability of benidipine to induce thermogenesis (increased rate of oxygen consumption) in isolated brown-fat cells from rats, mice and hamsters -and in intact cold-acclimated rats. RESULTS: Benidipine itself, or in combination with any dose of noradrenaline (NA), was totally unable to induce or augment thermogenesis in isolated brown-fat cells of any species tested. However, it markedly induced thermogenesis in intact animals (approx 60% increase over resting metabolic rate). This effect could be fully inhibited by propranolol. CONCLUSION: Benidipine is itself without thermogenic effect. The thermogenic response in-vivo (and thus presumably the anti-obesity effect) is probably secondary to a previously described general side-effect of calcium antagonists: a release of NA from sympathetic nerves, here most likely directly from nerves in the BAT. The antiobesity effect of benedipine is thus probably not due to its calcium channel blocking effect. PERSPECTIVES: It is probable that the anti-obesity effects of calcium antagonists reported in several models of genetically obese rodents (MSG-obese and agouti mice, SHHFaMcc-fa cp and JCR:LA-corpulent rats) are mediated via an indirect stimulation of BAT. To what extent calcium antagonists may induce similar effects in a clinical situation, is currently unknown.

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“…As a result, skin cooling or direct cooling of POA neurons modulates sympathetic stimulation of NST in BAT, as well as shivering thermogenesis [92][93][94]. The POA is also involved in the febrile response due to the integration of pyrogenic signals, such as prostaglandin E2, that stimulate the POA and activate BAT NST in a cAMP-dependent manner [95].…”

Section: Autonomic Control Of Body Temperaturementioning

confidence: 99%

Hypothalamic-autonomic control of energy homeostasis

et al. 2015

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Regulation of energy homeostasis is tightly controlled by the central nervous system (CNS). Several key areas such as the hypothalamus and brainstem receive and integrate signals conveying energy status from the periphery, such as leptin, thyroid hormones, and insulin, ultimately leading to modulation of food intake, energy expenditure (EE), and peripheral metabolism. The autonomic nervous system (ANS) plays a key role in the response to such signals, innervating peripheral metabolic tissues, including brown and white adipose tissue (BAT and WAT), liver, pancreas, and skeletal muscle. The ANS consists of two parts, the sympathetic and parasympathetic nervous systems (SNS and PSNS). The SNS regulates BAT thermogenesis and EE, controlled by central areas such as the preoptic area (POA) and the ventromedial, dorsomedial, and arcuate hypothalamic nuclei (VMH, DMH, and ARC). The SNS also regulates lipid metabolism in WAT, controlled by the lateral hypothalamic area (LHA), VMH, and ARC. Control of hepatic glucose production and pancreatic insulin secretion also involves the LHA, VMH, and ARC as well as the dorsal vagal complex (DVC), via splanchnic sympathetic and the vagal parasympathetic nerves. Muscle glucose uptake is also controlled by the SNS via hypothalamic nuclei such as the VMH. There is recent evidence of novel pathways connecting the CNS and ANS. These include the hypothalamic AMP-activated protein kinase-SNS-BAT axis which has been demonstrated to be a key modulator of thermogenesis. In this review, we summarize current knowledge of the role of the ANS in the modulation of energy balance.

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Injection of prostaglandin E2 into the anterior hypothalamic preoptic area activates brown adipose tissue thermogenesis in the rat

Cited by 52 publications

References 28 publications

TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity

TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity

Benidipine induces thermogenesis in brown adipose tissue by releasing endogenous noradrenaline: a possible mechanism for the anti-obesity effect of calcium antagonists

Hypothalamic-autonomic control of energy homeostasis

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