Hypothalamic control of brown adipose tissue in Zucker lean and obese rats. Effect of electrical stimulation of the ventromedial nucleus and other hypothalamic centres

Holt, S.J.; Wheal, H.V.; York, David A.

doi:10.1016/0006-8993(87)90292-7

Cited by 86 publications

(21 citation statements)

References 18 publications

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“…This unexpected observation suggests that moxonidine might increase energy expenditure via centrally inhibiting NPY neurons. The central regulation of the sympathetic out¯ow to brown adipose tissue involves several hypothalamic regions including the medial preoptic area, ventromedial nucleus and PVN (Freeman & Wellman, 1987;Holt et al, 1987), and administration of NPY intracerebroventricularly or into the PVN suppresses sympathetic a erent to brown adipose tissue (Egawa et al, 1991) and reduces UCP-1 mRNA (Billington et al, 1994). The NPY neurones are therefore suggested to be an important in¯uence, tonically inhibiting brown fat thermogenesis and so restraining energy expenditure (Bing et al, 1997).…”

Section: Discussionmentioning

confidence: 99%

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones

Chen

King

Pickavance

et al. 1999

British J Pharmacology

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1 The antihypertensive agent moxonidine, an imidazoline I i -receptor agonist, also induces hypophagia and lowers body weight in the obese spontaneously hypertensive rat, but the central mediation of this action and the neuronal pathways that moxonidine may interact with are not known. We studied whether moxonidine has anti-obesity e ects in the genetically-obese and insulinresistant fa/fa Zucker rat, and whether these are mediated through inhibition of the hypothalamic neuropeptide Y (NPY) neurones. 2 Lean and obese Zucker rats were given moxonidine (3 mg kg 71 day 71 ) or saline by gavage for 21 days. 3 Moxonidine decreased food intake throughout by 20% in obese rats (P50.001) and by 8% in lean rats (P50.001), and reduced weight gain that ®nal body weight was 15% lower in obese (P50.001) and 7% lower in lean (P50.01) rats than their untreated controls. Plasma insulin and leptin levels were decreased in moxonidine-treated obese rats (P50.01 and P50.05), but unchanged in treated lean rats. Uncoupling protein-1 gene expression in brown adipose tissue was stimulated by 40 ± 50% (P40.05) in both obese and lean animals given moxonidine. Obese animals given moxonidine showed a 37% reduction in hypothalamic NPY mRNA levels (P=0.01), together with signi®cantly increased NPY concentrations in the paraventricular nucleus (P50.05), but no changes in the arcuate nucleus or other nuclei; this is consistent with reduced NPY synthesis in the arcuate nucleus and blocked release of NPY in the paraventricular nucleus. In lean animals, moxonidine did not a ect NPY levels or NPY mRNA. 4 The hypophagic, thermogenic and anti-obesity e ects of moxonidine in obese Zucker rats may be partly due to inhibition of the NPY neurones, whose inappropriate overactivity may underlie obesity in this model.

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Section: Discussionmentioning

confidence: 99%

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones

Chen

King

Pickavance

et al. 1999

British J Pharmacology

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“…The weight gain in rats with NPY-induced obesity is greater than would be expected from the increased energy consumption alone [50] and recent studies have confirmed directly that NPY injected into the hypothalamus decreases energy expenditure [62] and can even induce hypothermia [54]. NPY probably acts in the PVN and other sites to inhibit the sympathetic activation of thermogenesis in BAT [63], thus simulating the 'autonomic imbalance' proposed to account for the thermogenic defect in genetically obese rodents [5,6].…”

Section: Does Npy Affect Energy Balance?mentioning

confidence: 99%

“…In ob/ob mice and f a / f a (fatty) Zucker rats, reduced energy expenditure may be the primary abnormality because it can be identified in very young (pre-obese) pups, before hyperphagia develops, and because obesity still develops when food intake is restricted to the level of their lean littermates. The defect in heat production does not apparently reside in the thermogenic tissues themselves, but rather in the hypothalamic control of the autonomic outflow which controls their activity; the parasympathetic system dominates, which tends to inhibit thermogenesis [5,6].…”

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confidence: 99%

Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Dryden

Frankish

Wang

et al. 1994

Eur J Clin Investigation

123

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Abstract. Obesity is a vast and ever-expanding problem in affluent societies, which we have so far failed to confront. Over 20% of Western European and North American adults are overweight to a degree which may potentially shorten their life expectancy. Obesity has well-known associations with non-insulin-dependent diabetes (NIDDM), hypertension, dyslipidaemia and coronary heart disease, as well as less obvious links with diseases such as osteoarthrosis and various malignancies; it also causes considerable problems through reduced mobility and decreased quality of life. The overall financial burden of obesity is impossible to calculate precisely, but may account for 6-8% of total health-care expenditure in North America [ 13 (similar estimates probably apply to Western Europe).Obesity is difficult to treat and many patients remain obstinately overweight despite our best efforts. The available options range from behavioural therapy to gastrointestinal surgery and include numerous drugs designed to suppress appetite or increase energy expenditure. As in many other areas of medicine, the length and diversity of this list are reliable signs that effective treatment is still beyond our reach.This article argues that new anti-obesity drugs may emerge from recent advances in understanding the control of energy balance in rodents. The discussion is structured around neuropeptide Y (NPY), a major brain peptide which at present appears to be important in regulating energy balance and seems a promising candidate for therapeutic exploitation.

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“…Electrical stimulation of the VMH of urethane-anaesthetized, 21-24 TC-acclimated Sprague-Dawley, lean and obese hooded rats has been shown to evoke both a rise in interscapular BAT temperature (Perkins et al 1981;Holt et al 1987) or no IBAT temperature change (Freeman & Wellman, 1987 Freeman & Wellman (1987) who also used the same sex and strain of rats and similar stimulus parameters (30 s train of biphasic square-wave pulses of 0-5 s, 60 Hz, 100 gA). Whether these 21 TC-acclimated rats were maintained at 37 0C (Fig.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, Freeman & Wellman (1987), using urethane-anaesthetized rats acclimated to 23 + 1 C, indicated that unilateral stimulation of the anterior hypothalamus (AH), medial preoptic region (MPO), paraventricular nucleus (PVN) or dorsomedial nucleus (DMN) but not the VMH or caudal hypothalamus (CH) caused a rise in IBAT temperature in those rodents. Interestingly, Holt, Wheal & York (1987), using 7-week-old urethane-anaesthetized lean and obese Zucker rats, reported that electrical stimulation of the VMH, supraoptic nucleus (SON) and AH nuclei caused a similar increase in IBAT temperature of both lean and obese rats. The magnitude of the rise of the IBAT temperature was similar for both lean and obese rats but the duration of the hypothermic response was greater in the obese animals.…”

Section: Introductionmentioning

confidence: 99%

Brown adipose tissue thermogenic responses of rats induced by central stimulation: effect of age and cold acclimation.

Thornhill

Halvorson

1990

The Journal of Physiology

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SUMMARY1. Urethane-anaesthetized, age-matched cold-(4 TC) and room (21 'C)-acclimated groups of Sprague-Dawley rats were given repeated (three) ventromedial hypothalamic electrical stimulations. Interscapular brown adipose tissue (IBAT), colonic, surface tail temperatures and blood pressure were monitored before and after each electrical stimulation. Propranolol HCl (2-5 mg kg-' i.v.) was given 10 min prior to the last (third) ventromedial hypothalamic stimulation.2. Repeated electrical stimulation of the ventromedial hypothalamic (VMH) nucleus to either small or large rats (kept at 21 TC) caused no significant change in interscapular brown fat, colonic or surface temperatures compared to respective pre-stimulation control values whereas mean arterial pressure was slightly but significantly increased during the 30 s stimulation period.3. Electrical stimulation of the ventromedial hypothalamic nucleus of small or large rats, kept at 4 TC for 3 weeks prior to testing, caused significant (> 0-25 and > 0 40 TC, respectively) rises in interscapular BAT temperature from respective prestimulation control values. Colonic temperatures increased following ventromedial hypothalamic electrical stimulation only in the small, 4 TC-acclimated group whereas surface tail temperatures did not significantly change after stimulation of either cold-exposed group. Mean arterial pressures were significantly increased during ventromedial hypothalamic electrical stimulation in both 4 TC-acclimated groups, compared to pre-stimulation control levels and, in addition, were above those of agematched rats kept at 21 'C. Intravenous propranolol, which decreased interscapular brown fat and colonic temperatures in all groups, blocked the rise in interscapular brown fat and colonic temperatures of the 4°C-acclimated rats following the last electrical stimulation of the ventromedial hypothalamic nucleus.4. In vitro biochemical analysis of the interscapular brown fat pads of another four groups of age-matched, small and large 21 and 4°C-acclimated rats revealed that the thermogenic capacity of the 4 "C-acclimated groups was, in all cases, significantly increased from age-matched groups previously kept at 21 "C, as shown by significant increases in brown adipose tissue mass, BAT DNA and protein content, BAT mitochondrial protein and BAT mitochondrial GDP binding.5. Other experiments using urethane-anaesthetized. age-matched male Sprague-MS 7805 J. THORNHILL AND I. HALVORSON Dawley rats previously maintained at 21 or 4 TC for 3 weeks prior to testing, with their core temperature maintained at 37 0C during experimentation, revealed similar results as above. Interscapular brown fat temperatures were significantly elevated (> 0 50 TC) in the 4 0C-acclimated group following electrical stimulation of the ventromedial hypothalamic nucleus but not in those rats kept at 21 'C. However, intravenous infusion of noradrenaline HCl (20 jtg ml-1) for 10 min significantly raised interscapular brown fat temperatures (> 0-80 TC) in room (21 'C)-acclimated rats, yet ...

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Hypothalamic control of brown adipose tissue in Zucker lean and obese rats. Effect of electrical stimulation of the ventromedial nucleus and other hypothalamic centres

Cited by 86 publications

References 18 publications

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones

The effect of moxonidine on feeding and body fat in obese Zucker rats: role of hypothalamic NPY neurones

Neuropeptide Y and energy balance: one way ahead for the treatment of obesity?

Brown adipose tissue thermogenic responses of rats induced by central stimulation: effect of age and cold acclimation.

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