The medial preoptic nucleus as a site of the thermogenic and metabolic actions of melanotan II in male rats

2014 ◽  
Vol 307 (2) ◽  
pp. R158-R166 ◽  
Author(s):  
Boris Monge-Roffarello ◽  
Sebastien M. Labbe ◽  
Christophe Lenglos ◽  
Alexandre Caron ◽  
Damien Lanfray ◽  
...  
Keyword(s):  
Metabolic Effects ◽  
Male Rats ◽  
Hypothalamic Nucleus ◽  
Preoptic Nucleus ◽  
Iodothyronine Deiodinase ◽  
Interscapular Brown Adipose Tissue ◽  
Medial Preoptic Nucleus ◽  
Brown Adipose ◽  
A Site ◽  
Melanotan Ii

The present study was designed to investigate the role of the medial preoptic nucleus (MPO) as a site of the thermogenic and metabolic effects of the α-melanocyte-stimulating hormone analog melanotan II (MTII). We also assessed the involvement of the dorsomedial hypothalamic nucleus (DMH) by investigating the effects of the MPO infusion of MTII in rats with DMH lesions produced by kainic acid. Infusion of MTII in the MPO led to increases in interscapular brown adipose tissue (iBAT) temperature and iBAT uptake of 14C-bromopalmitate. Both increases were blocked by DMH lesions. iBAT temperature increase (area under curve) and 14C-bromopalmitate uptake emerged as two correlated variables ( r = 0.63, P < 0.001). DMH lesions also blocked MTII-induced expression of mRNAs coding for proteins involved in 1) thermogenesis [type II iodothyronine deiodinase ( Dio2) and peroxisome proliferator-activated receptor gamma coactivator 1-α ( Pgc1α)], 2) lipolysis [hormone-sensitive lipase ( Hsl)], and 3) lipogenesis [diacylglycerol-O-acyltransferase 2 ( Dgat2), fatty acid synthase ( Fas)], in iBAT of rats killed 1 h after MPO infusion of MTII. MTII also stimulated expression of genes in iWAT but only in rats with DMH lesions. These genes included glucose transporter member 4 ( Glut4), glycerol-3-phosphate acyltransferase 3 ( Gpat3), Dgat1, Dgat2, triglyceride lipase ( Atgl), Hsl, and carnitine palmitoyltransferase 1β ( Cpt1β). Altogether, the present results reveal the MPO as a site of the thermogenic and metabolic actions of MTII. They also contribute to establish the MPO-DMH duet as a significant target for melanocortins to modulate energy homeostasis.

scholarly journals The PVH as a Site of CB1-Mediated Stimulation of Thermogenesis by MC4R Agonism in Male Rats

Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3448-3458 ◽  
Author(s):  
Boris Monge-Roffarello ◽  
Sebastien M. Labbe ◽  
Marie-Claude Roy ◽  
Marie-Laurence Lemay ◽  
Estelle Coneggo ◽  
...  
Keyword(s):  
Uncoupling Protein ◽  
Third Ventricle ◽  
Male Rats ◽  
Whole Body ◽  
Hypothalamic Nucleus ◽  
Peroxisome Proliferator ◽  
Iodothyronine Deiodinase ◽  
Brown Adipose ◽  
Series Of Experiments ◽  
The Brain

Abstract The present study was designed to investigate the involvement of the cannabinoid receptor 1 (CB1) in the stimulating effects of the melanocortin-4 receptor (MC4R) agonism on whole-body and brown adipose tissue (BAT) thermogenesis. In a first series of experiments, whole-body and BAT thermogenesis were investigated in rats infused in the third ventricle of the brain with the MC4R agonist melanotan II (MTII) and the CB1 agonist δ9-tetrahydrocannabinol (δ9-THC) or the CB1 antagonist AM251. Whole-body thermogenesis was measured by indirect calorimetry and BAT thermogenesis assessed from interscapular BAT (iBAT) temperature. δ9-THC blunted the effects of MTII on energy expenditure and iBAT temperature, whereas AM251 tended to potentiate the MTII effects. δ9-THC also blocked the stimulating effect of MTII on 14C-bromopalmitate and 3H-deoxyglucose uptakes in iBAT. Additionally, δ9-THC attenuated the stimulating effect of MTII on the expression of peroxisome proliferator-activated receptor-γ coactivator 1-α (Pgc1α), type II iodothyronine deiodinase (Dio2), carnitine palmitoyltransferase 1B (Cpt1b), and uncoupling protein 1 (Ucp1). In a second series of experiments, we addressed the involvement of the paraventricular hypothalamic nucleus (PVH) in the CB1-mediated effects of MTII on iBAT thermogenesis, which were assessed following the infusion of MTII in the PVH and δ9-THC or AM251 in the fourth ventricle of the brain. We demonstrated the ability of δ9-THC to blunt MTII-induced iBAT temperature elevation. δ9-THC also blocked the PVH effect of MTII on 14C-bromopalmitate uptake as well as on Pgc1α and Dio2 expression in iBAT. Altogether the results of this study demonstrate the involvement of the PVH in the CB1-mediated stimulating effects of the MC4R agonist MTII on whole-body and BAT thermogenesis.

scholarly journals Stimulatory, but not anxiogenic, doses of caffeine act centrally to activate interscapular brown adipose tissue thermogenesis in anesthetized male rats

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
L. Van Schaik ◽  
C. Kettle ◽  
R. Green ◽  
W. Sievers ◽  
M. W. Hale ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Basolateral Amygdala ◽  
Free Breathing ◽  
Male Rats ◽  
Central Administration ◽  
Hypothalamic Area ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

AbstractThe role of central orexin in the sympathetic control of interscapular brown adipose tissue (iBAT) thermogenesis has been established in rodents. Stimulatory doses of caffeine activate orexin positive neurons in the lateral hypothalamus, a region of the brain implicated in stimulating BAT thermogenesis. This study tests the hypothesis that central administration of caffeine is sufficient to activate BAT. Low doses of caffeine administered either systemically (intravenous [IV]; 10 mg/kg) and centrally (intracerebroventricular [ICV]; 5–10 μg) increases BAT thermogenesis, in anaesthetised (1.5 g/kg urethane, IV) free breathing male rats. Cardiovascular function was monitored via an indwelling intra-arterial cannula and exhibited no response to the caffeine. Core temperature did not significantly differ after administration of caffeine via either route of administration. Caffeine administered both IV and ICV increased neuronal activity, as measured by c-Fos-immunoreactivity within subregions of the hypothalamic area, previously implicated in regulating BAT thermogenesis. Significantly, there appears to be no neural anxiety response to the low dose of caffeine as indicated by no change in activity in the basolateral amygdala. Having measured the physiological correlate of thermogenesis (heat production) we have not measured indirect molecular correlates of BAT activation. Nevertheless, our results demonstrate that caffeine, at stimulatory doses, acting via the central nervous system can increase thermogenesis, without adverse cardio-dynamic impact.

scholarly journals The thermogenic effect of nesfatin-1 requires recruitment of the melanocortin system

2017 ◽  
Vol 235 (2) ◽  
pp. 111-122 ◽  
Author(s):  
Riccardo Dore ◽  
Luka Levata ◽  
Sogol Gachkar ◽  
Olaf Jöhren ◽  
Jens Mittag ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Heat Loss ◽  
Central Administration ◽  
Melanocortin System ◽  
Direct Calorimetry ◽  
Iodothyronine Deiodinase ◽  
Interscapular Brown Adipose Tissue ◽  
Peripheral Tissues ◽  
Dry Heat ◽  
Brown Adipose

Nesfatin-1 is a bioactive polypeptide expressed both in the brain and peripheral tissues and involved in the control of energy balance by reducing food intake. Central administration of nesfatin-1 significantly increases energy expenditure, as demonstrated by a higher dry heat loss; yet, the mechanisms underlying the thermogenic effect of central nesfatin-1 remain unknown. Therefore, in this study, we sought to investigate whether the increase in energy expenditure induced by nesfatin-1 is mediated by the central melanocortin pathway, which was previously reported to mediate central nesfatin-1´s effects on feeding and numerous other physiological functions. With the application of direct calorimetry, we found that intracerebroventricular nesfatin-1 (25 pmol) treatment increased dry heat loss and that this effect was fully blocked by simultaneous administration of an equimolar dose of the melanocortin 3/4 receptor antagonist, SHU9119. Interestingly, the nesfatin-1-induced increase in dry heat loss was positively correlated with body weight loss. In addition, as assessed with thermal imaging, intracerebroventricular nesfatin-1 (100 pmol) increased interscapular brown adipose tissue (iBAT) as well as tail temperature, suggesting increased heat production in the iBAT and heat dissipation over the tail surface. Finally, nesfatin-1 upregulated pro-opiomelanocortin and melanocortin 3 receptor mRNA expression in the hypothalamus, accompanied by a significant increase in iodothyronine deiodinase 2 and by a nonsignificant increase in uncoupling protein 1 and peroxisome proliferator-activated receptor gamma coactivator-1 alpha mRNA in the iBAT. Overall, we clearly demonstrate that nesfatin-1 requires the activation of the central melanocortin system to increase iBAT thermogenesis and, in turn, overall energy expenditure.

Thermogenesis after lateral hypothalamic lesions: contributions of brown adipose tissue

1988 ◽  
Vol 255 (5) ◽  
pp. E708-E715 ◽  
Author(s):  
S. W. Corbett ◽  
L. N. Kaufman ◽  
R. E. Keesey
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Nervous Activity ◽  
Male Rats ◽  
Sympathetic Nervous Activity ◽  
Primary Role ◽  
Interscapular Brown Adipose Tissue ◽  
Lateral Hypothalamic ◽  
Brown Adipose ◽  
The Hours

The role of brown adipose tissue in the thermogenic response to lateral hypothalamic (LH) lesions was investigated. Interscapular brown adipose tissue (IBAT) temperatures were measured during the hours following bilateral electrolytic LH lesions in male rats sedated with pentobarbital sodium. Local temperature changes were also recorded from skin and colonic sites. Consistent with the view that brown adipose tissue plays a primary role in the hyperthermia produced by LH lesions, IBAT depot temperature rose before, at a faster rate, and to a higher level than the other sites. In two subsequent experiments, oxygen consumption, activity, and core temperature were monitored in freely moving male rats with LH lesions, both in warm (25 degrees C) and cold (5 degrees C) environments. The results of these experiments provide some support for the view that LH lesions produce an increase in the regulated level of body temperature. This hyperthermic and hypermetabolic state seems to be mediated, in part, by brown fat thermogenesis and may represent a general increase in sympathetic nervous activity induced by the lesion.

Decreased brown adipose tissue thermogenic activity following a reduction in brain serotonin by intraventricular p-chlorophenylalanine

1987 ◽  
Vol 7 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Nigel J. Fuller ◽  
Dorothy M. Stirling ◽  
Stephen Dunnett ◽  
Gavin P. Reynolds ◽  
Margaret Ashwell
Keyword(s):  
Adipose Tissue ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Male Rats ◽  
Brain Serotonin ◽  
Interscapular Brown Adipose Tissue ◽  
Sympathetic Control ◽  
Brown Adipose ◽  
Ad Libitum ◽  
Established Role

The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fed ad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake.

Prolactin- and testosterone-induced inhibition of LH secretion after orchidectomy: role of catecholaminergic neurones terminating in the diagonal band of Broca, medial preoptic nucleus and median eminence

1996 ◽  
Vol 148 (2) ◽  
pp. 291-301 ◽  
Author(s):  
S-K Park ◽  
D A Strouse ◽  
M Selmanoff
Keyword(s):  
Median Eminence ◽  
Inhibitory Effect ◽  
Male Rats ◽  
Testosterone Replacement ◽  
Preoptic Nucleus ◽  
Medial Preoptic Nucleus ◽  
Diagonal Band ◽  
Lh Release ◽  
Diagonal Band Of Broca ◽  
Lh Secretion

Abstract Central catecholaminergic neurones projecting to specific hypothalamic structures are involved in stimulating and inhibiting the activity of the GnRH-containing neurosecretory neurones. Both testosterone and elevated circulating prolactin (PRL) levels inhibit postcastration LH release. Three groups of adult male rats were orchidectomized and adrenalectomized, received corticosterone replacement and were: (i) administered purified ovine PRL (oPRL; 2400 μg/s.c. injection) or (ii) its diluent, polyvinylpyrrolidone (PVP), every 12 h, or (iii) received physiological testosterone replacement for 2 days. At 0, 2 and 6 days postcastration, norepinephrine (NE), epinephrine (E) and dopamine (DA) turnover were estimated by the α-methyl-p-tyrosine method in three micro-dissected hypothalamic structures: the diagonal band of Broca at the level of the organum vasculosum of the lamina terminalis (DBB(ovlt)), the medial preoptic nucleus (MPN) and the median eminence (ME). In control (PVP-treated) rats, serum LH concentrations increased eightfold at 2 and 6 days postcastration and this rise was prevented by testosterone. oPRL treatment transiently suppressed LH secretion at 2 but not 6 days postcastration. Castration significantly decreased basal rat PRL (rPRL) levels at 2 and 6 days and testosterone administration partially prevented this effect. NE turnover in the ME and E turnover in the MPN increased markedly at 2 and 6 days postcastration, and testosterone replacement for 2 days prevented these increases. Thus, noradrenergic neurones innervating the ME and adrenergic neurones innvervating the MPN may drive postcastration LH secretion by providing stimulatory afferent input to the GnRH neurones. It was striking to observe that oPRL blocked the increases in both ME NE and MPN E turnover at 2 but not 6 days postcastration. Hence, oPRL may transiently suppress LH release by an inhibitory action on these NE and E neurones. DA turnover in the DBB(ovlt) was significantly decreased by 6 days postcastration. Testosterone-treated (2 days postcastration) and oPRL-treated (2 and 6 days postcastration) rats exhibited turnover values indistinguishable from day 0 controls. Hence, the A14 dopaminergic neurones, which synapse on GnRH neurones in the rostral preoptic area and may exert an inhibitory effect on them, are positively regulated by PRL and perhaps by testosterone as well. Autoregulatory feedback suppression of endogenous rPRL secretion by oPRL was observed both 2 and 6 days postcastration. In contrast to the A14 dopaminergic neurones, turnover in the A12 tuberoinfundibular dopaminergic (TIDA) neurones innervating the ME increased significantly by 6 days postcastration in control rats while oPRL administration further increased ME DA turnover at both 2 and 6 days. Hence, autofeedback regulation of rPRL secretion persists through at least 6 days of oPRL exposure temporally associated with markedly increased turnover in the TIDA neurones. In summary, our results support the hypothesis that the inhibitory effect of PRL on postcastration LH release is mediated by suppression of the activity of NE neurones innervating the ME and E neurones terminating in the MPN which, with time, become refractory to continued PRL exposure. Journal of Endocrinology (1996) 148, 291–301

scholarly journals EPIGENOMIC EFFECTS OF EXPOSURE OF PREGNANT RATS TO LOW DOSE OF BISPHENOL A REGARDING THE NEUROENDOCRINE SYSTEM OF THE MALE F1 GENERATION (short communication)

2021 ◽  
pp. 23-28
Author(s):  
Alexander Reznikov ◽  
Olha Sachynska ◽  
Аnna Lymareva ◽  
Lyubov Polyakova
Keyword(s):  
Sexual Behavior ◽  
Bisphenol A ◽  
Low Dose ◽  
Male Offspring ◽  
Male Rats ◽  
Normal Male ◽  
Potential Hazard ◽  
Preoptic Nucleus ◽  
Female Behavior ◽  
Medial Preoptic Nucleus

Aim: To study the long-term effects of exposure of pregnant Wistar rats to low dose of bisphenol A (BPA) by measuring to the level of steroid hormones and sexual behavior of adult male offspring of the first generation. Material and research methods: BPA as part of the Dorfman gel was gavaged during the last week of pregnancy, when androgen-dependent sexual brain differentiation occurs, in a daily dose of 25 mcg/kg b.w. (threshold teratogenic dose). Male sexual behavior was evaluated by proceptive reactions, the duration of latent and refractory periods, the number of mounts, intromissions and ejaculations in the presence of a receptive female. Female sexual behavior was assessed by lordosis reactions of orchidectomized and activated by the introduction of estradiol and progesterone males in the presence of a normal male. A neuromorphological analysis of the sex-dimorphic area of the brain, the medial preoptic nucleus of the hypothalamus, was performed by histological examination and karyometry of neurons. Results: Prenatally administered BPA caused a very slight increase in the anogenital distance in newborn animals and did not affect the terms of puberty. The levels of testosterone and corticosterone in the blood plasma of males of 6 months of age did not differ from the control indices. At 10 months of age, all experimental males showed sharply weakened sexual motivation for mating with females, and in 4 from 5 animals, copulative components of sexual behavior were absent. There was no ejaculations in the 5th male as well, while numbers of the mounts without intromissions and ones with intromissions significantly reduced. In the BPA group, all descendants showed active female behavior in the presence of a normal male, which manifested in lordosis reactions and a high lordosis index. According to the histological study of medial preoptic nucleus, the activity of neurocytes in the male offspring of BPA-exposed females was significantly reduced, and their nuclei volume distribution was some different from the control. Conclusions: The data obtained indicate epigenetic disorders of the sexual brain differentiation program due to the prenatal exposure to BPA in dose that does not cause significant teratogenic effects. This should be taken into account when evaluating the potential hazard of BPA for reproductive health. Key words: bisphenol A, prenatal effect, male rats, sexual behavior, corticosterone, testosterone.

Neuronal activity changes of ventromedial hypothalamic neurons and associated temperature responses in rats following scrotal thermal stimulation

1993 ◽  
Vol 71 (8) ◽  
pp. 604-610 ◽  
Author(s):  
Q. Li ◽  
J. Thornhill
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Firing Rate ◽  
Neuronal Activity ◽  
Tap Water ◽  
Hypothalamic Nucleus ◽  
Hypothalamic Neurons ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Normothermic Group

Experiments were conducted to determine whether ventromedial hypothalamic (VMH) neurons were responsive to thermal warming or cooling of the scrotum. Extracellular neuronal activity of VMH neurons was monitored in anesthetized groups of normothermic (core temperature maintained at 37 °C) or hypothermic (core temperatures allowed to decrease, 33.3 ± 1.1 °C) male, Sprague–Dawley rats along with colonic (Tc), interscapular brown adipose tissue (TIBAT), tail (Tt), and scrotal (Tsc) temperatures during 30-min periods of scrotal cooling (small ice pack) or scrotal warming (small sealed pack containing 40 °C tap water). In the normothermic group (65 VMH neurons recorded in total), 20 VMH neurons (31%) were classified as warm-responsive neurons (WRNs) (i.e., increased firing rate with scrotal warming and (or) decreased firing rates with scrotal cooling); 7 VMH neurons (11%) were classified as cold-responsive neurons (CRNs) (i.e., increased firing rate with scrotal cooling and (or) decreased firing rate with scrotal warming); and 38 VMH neurons (58%) were thermal nonresponsive neurons (TNRNs). In the hypothermic group (total of 85 VMH neurons recorded), 14 neurons (16%) were WRNs, 15 neurons (18%) were CRNs, and 56 neurons (66%) were TNRNs. Results indicated that VMH neurons can respond selectively to changes in scrotal temperature, as previously shown for preoptic–anterior hypothalamic neurons. Scrotal cooling and warming caused marked changes in T(sc) values in both the hypothermic and normothermic rats, but significant increases in TIBAT values indicative of brown adipose tissue thermogenesis did not occur.Key words: ventromedial hypothalamic nucleus, extracellular neuronal recording, temperature, scrotum.

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