Innervating Interscapular Brown Adipose Tissue Research Articles

Administration of muscimol into the posterior hypothalamus reduces hyperthermia induced by hippocampal neostigmine injection

The firing rate of the sympathetic nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures ( T IBAT and T C) and oxygen (O 2) consumption were monitored in urethane-anesthetized male Sprague–Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after an injection of neostigmine (5×10 −7 mol in 1 μl of saline) into the hippocampus and a bilateral administration of a GABA a-agonist, muscimol (28 ng in 0.5 μl of saline, per side) into the posterior hypothalamus. The same variables were recorded in other rats, but the muscimol was replaced by saline. Control animals were used with muscimol or saline alone. The results show an increase of sympathetic firing rate, T IBAT, T C and O 2 consumption after neostigmine injection. Muscimol significantly reduces this enhancement. The findings suggest that hippocampus controls the sympathetic and thermogenic activation induced by neostigmine through an influence on GABAergic tone of the posterior hypothalamus.

Intracerebroventricular injection of prostaglandin E 1 changes concentrations of biogenic amines in the posterior hypothalamus of the rat

Since the posterior hypothalamus (PH) plays a key role in the control of body temperature, the aim of this study was to evaluate the changes in adrenaline, noradrenaline and dopamine levels in the PH during the hyperthermia induced by prostaglandin E 1 (PGE 1). The concentration of adrenaline, noradrenaline and dopamine in the PH, the firing rate of the sympathetic nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (T IBAT and T C) were monitored in 12 urethane-anaesthetized male Sprague–Dawley rats before and after an intracerebroventricular injection of 500 ng PGE 1 dissolved in 2 μl of 0.9% NaCl saline solution or only saline. The catecholamines were collected using a microdialysis probe and quantified by HPLC. The results showed that PGE 1 caused a significant increment in the concentration of adrenaline from 15.83±2.69 to 34.95±3.9 ng ml −1 and of dopamine from 35.15±4.48 to 55.68±6.21 ng ml −1. A significant decrease in the level of noradrenaline from 18.75±2.05 to 8.56±2.26 ng ml −1 was registered. The firing rate of sympathetic nerves to IBAT was increased from 100±0% to 204.83±15.22% by PGE 1. T IBAT and T C rose respectively from 36.91±0.15°C to 38.88±0.29°C, and from 36.7±0.15°C to 38.13±0.36°C after the injection of PGE 1. The changes in adrenaline and noradrenaline occurred during the first 20 min as did the changes in temperature and firing rate, while the change in dopamine was delayed until 21–60 min after the PGE 1 injection. No significant change of analyzed variables was found in the control rats. These findings suggest that these biogenic amines of the PH are involved in the control of the sympathetic and thermogenic changes induced by PGE 1.

Intracerebroventicular injection of prostaglandin E 1 increases γ-aminobutyric acid level in the posterior hypothalamus

The level of γ-aminobutyric acid (GABA) in the posterior hypothalamus, the firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures ( T IBAT and T c) were monitored in urethane-anesthetized male Sprague–Dawley rats. These variables were measured before and after an intracerebroventricular injection of 500 ng prostaglandin E 1 (PGE 1). The same variables were monitored in other rats with saline injection. The results showed that PGE 1 caused an increase in GABA concentration, firing rate, T IBAT, T c. These findings suggest that GABA-ergic tone in the posterior hypothalamus is important in the control of the sympathetic and thermogenic changes induced by PGE 1.

L-threonine injection into PPC modifies food intake, lateral hypothalamic activity, and sympathetic discharge.

Food intake and the firing rate of lateral hypothalamic neurons and nerves innervating interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures, were monitored in male Sprague-Dawley rats fed a threonine-free diet. These variables were measured before and after a bilateral injection of L-threonine (2 nmol into each side) into the prepiriform cortex (PPC). The same variables were also monitored in 1) rats fed a threonine-free diet and injected with saline, 2) animals fed a standard diet and injected with L-threonine, and 3) rats fed a standard diet and injected with saline. The results showed that injection of L-threonine into PPC increases food intake and firing rate of lateral hypothalamic neurons, whereas it decreases the sympathetic discharge and body temperature in animals fed a threonine-free diet. No changes were found in the animals fed a standard diet. These findings suggest a correlation between 1) threonine level in the PPC and 2) lateral hypothalamic activity and sympathetic discharge to IBAT.

Lysine acetylsalicylate modifies aphagia and thermogenic changes induced by lateral hypothalamic lesion.

These experiments test the effect of intraperitoneal injection of lysine acetylsalicylate on 1) food intake and 2) the sympathetic and thermogenic changes induced by lesion of the lateral hypothalamus (LH). Food intake, firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), and IBAT and colonic temperatures (TIBAT and TC) were monitored in male Sprague-Dawley rats lesioned in the LH. These variables were measured before and after intraperitoneal injection of lysine acetylsalicylate. The same variables were also monitored in 1) lesioned rats with intraperitoneal administration of saline, 2) sham-lesioned animals with intraperitoneal injection of lysine acetylsalicylate, and 3) sham-lesioned rats with intraperitoneal injection of saline. The results show that lysine acetylsalicylate modifies the aphagia by increasing food intake and also reduces the enhancements in firing rate, TIBAT, and TC induced by LH lesion. These findings suggest that prostaglandin synthesis plays a key role in the control of eating behavior in LH-lesioned rats by acting on the sympathetic and thermogenic changes induced by LH lesion.

Neostigmine in the hippocampus increases thermogenesis and T4-to-T3 conversion.

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (TIBAT and TC), and O2 consumption were monitored in urethan-anesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a neostigmine (5 x 10(-7) mol) or saline injection in the hippocampus. The blood level of 3,5,3'-triiodothyronine and L-thyroxine (T3 and T4) and the 5'-deiodinating activity of IBAT, liver, and kidneys were determined in other rats with neostigmine or saline injection. The results showed that neostigmine injection increased firing rate, TIBAT, TC, O2 consumption, blood level of T3, and 5'-deiodinating activity of IBAT. No change was found in the T4 level and in 5'-deiodinating activity of the liver and kidneys. These findings suggest that neostigmine injection in the hippocampus increases heat production by stimulating sympathetic nerves to IBAT and by elevating the blood level of T3.

Lateral hypothalamic lesion induces sympathetic stimulation and hyperthermia by activating synthesis of cerebral prostaglandins

This experiment tests the effect of intracerebroventricular (icv) injection of lysine acetylsalicylate on the sympathetic and thermogenic changes induced by lesion of the lateral hypothalamus (LH). The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures (T IBAT and T c) were monitored in urethane-anaesthetized male Sprague-Dawley rats lesioned in the LH. These variables were measured before and after an icv injection of Img lysine acetylsalicylate. The same variables were also monitored in: a) lesioned rats with icv administration of saline; b) sham-lesioned animals with icv injection of lysine acetylsalicylate; c) sham-lesioned rats with icv injection of saline. In an additional experiment, the same variables were monitored after an icv injection of lysine acetylsalicylate or saline in rats with LH lesion performed 48 h before the icv injection. The results show that lysine acetylsalicylate injection reduces the increases in firing rate, T IBAT, and T c induced by LH lesion. These findings suggest that cerebral prostaglandin synthesis plays a key role in the sympathetic and thermogenic changes following LH lesion.

N G-methyl-L-arginine increases the hyperthermic effects of prostaglandin E 1

The sympathetic firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures (T IBAT and T C) were monitored in urethane-anaesthetized male Sprague-Dawley rats. These variables were measured for a period of 40 min before (baseline values) and 40 min after a 2 mg N G-methyl-L-arginine (NMA) injection plus an intracerebroventricular administration of 500 ng prostaglandin E 1 (PGE 1) into a lateral cerebral ventricle. No drug was injected in control rats. The results show that NMA enhances the increases in firing rate, T IBAT and T C induced by PGE 1. These findings indicate that an inhibitor of nitric oxide synthesis, such as NMA, increases the sympathetic and thermogenic responses to injection of PGE 1.

Nitric oxide reduces body temperature and sympathetic input to brown adipose tissue during PGE 1-hyperthermia

The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT) and IBAT and colonic temperatures (T IBAT and T c) were monitored in urethane-anaesthetized male Sprague-Dawley rats. These variables were measured for 40 min before (baseline values) and 40 min after a 4 μmoles l-arginine ( l-arg) or 400 nmoles nitroprusside (NP) injection in a lateral cerebral ventricle and an intracerebroventricular administration of 500 ng prostaglandin E 1 (PGE 1). The same variables were monitored in other rats with l-arg or NP or PGE 1 administration alone. No drug was injected in control rats. The results show that l-arg or NP injection reduces the increases in firing rate, T IBAT, T c induced by PGE 1 These findings suggest that nitric oxide is important in the control of thermogenic changes during the PGE 1 hyperthermia.

Non-shivering thermogenesis during prostaglandin E 1 fever in rats: role of the cerebral cortex

We have tested the hypothesis that there is a role for the cerebral cortex in the control of non-shivering thermogenesis during fever induced by prostaglandin E 1 (PGE 1). While under urethan anesthesia, the firing rate of nerves innervating interscapular brown adipose tissue (IBAT), IBAT and colonic temperatures ( T IBAT and T c) and oxygen (O 2) consumption were monitored during the fever from PGE 1 injection (400 and 800 ng) in a lateral cerebral ventricle in controls and in functionally decorticated Sprague-Dawley rats. Rats were functionally decorticated by applying 3.3 M KCl solution on the frontal cortex which causes cortical spreading depression (CSD). Pyrogen injections caused dose-related increases in firing rate, T IBAT, T c and O 2 consumption and CSD reduced these enhancements. Our findings indicate that the cerebral cortex could be involved in the control of non-shivering thermogenesis during PGE 1-induced febrile response.

Nitric oxide reduces the thermogenic changes induced by lateral hypothalamic lesion

The experiment described here tests the effect of intracerebroventricular (icv) injection of nitric oxide (NO) precursors, such as L-arginine (L-arg) and nitroprusside (NP), on the thermogenic changes induced by lesion of the lateral hypothalamus (LH). The firing rate of the nerves innervating interscapular brown adipose tissue (IBAT), along with IBAT and colonic temperatures (T IBAT and T C) were monitored in urethane-anesthetized male Sprague-Dowley rats lesioned in the LH. These variables were measured before and after and icv injection of 4 μmol L-arg or 400 nmol NP. The same variables were also monitored in: a) lesioned rats with icv administration of saline; b) sham-lesioned animals with icv injection of L-arg or NP; c) sham-lesioned rats with icv injection of saline. The results show that L-arg or NP injection reduces the increases in firing rate, T IBAT, and T C induced by LH lesion. These findings suggest that NO plays a key role in the thermogenic changes following LH lesion.

Sympathetic nerve activity after discrete hypothalamic injections of l-glutamate

In these experiments L-glutamate, an amino acid which stimulates neuronal discharge, was microinjected into several hypothalamic nuclei and the resultant changes in electrical firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) were measured. Three patterns of response were seen. A single large stimulatory response was seen when L-glutamate was microinjected into the ventromedial hypothalamus (VMH). Microinjection of L-glutamate into the paraventricular nucleus (PVN) produced a predominantly stimulatory response which was of smaller magnitude than the VMN. However in three animals L-glutamate in the PVN decreased firing rate and in one animal a biphasic response was observed. The second pattern was a decrease in sympathetic activity to IBAT which was the predominant pattern following injection of L-glutamate into the dorsomedial hypothalamus (DMH). However, a biphasic pattern was also observed. Injection of L-glutamate into the lateral hypothalamic area (LHA) produced 3 patterns of response; an increase, a decrease; or a biphasic response in nearly equal numbers of animals. The predominant response to L-glutamate in the preoptic area (POA) was biphasic. These data are consistent with the hypothesis that the VMH is the predominant stimulatory site for activation of the sympathetic nervous system to IBAT in the rat. The DMH and LHA appear to be the predominant inhibitory areas.

Effect of norepinephrine, serotonin and tryptophan on the firing rate of sympathetic nerves

The firing rate of sympathetic nerves innervating interscapular brown adipose tissue (IBAT) has been recorded following microinjection of monoamines into the ventromedial (VMN) and paraventricular nuclei (PVN). Microinjection of norepinephrine (10 nmol) into the paraventricular nucleus produced a biphasic pattern in the firing rate of the sympathetic efferent nerves to IBAT. There was an initial dose-related 20% inhibition of firing rate followed 2 min later by 10% increase above control. When 10 times as much norepinephrine was injected into the ventromedial hypothalamus, there was a small 5% decrease in firing rate and a later significant dose-related increase in firing rate. These effects of norepinephrine were blocked by phentolamine, an α-adrenergic blocking drug, but not by propranolol, a ß-adrenergic blocking drug. Injection of serotonin into the paraventricular nucleus produced a short-lived but significant increase in firing rate of sympathetic nerves to brown adipose tissue. Comparable amounts of serotonin injected into the ventromedial nucleus produced a similar magnitude of increase in firing rate which lasted longer. There was a clear dose-response effect of serotonin injected into the PVN, but a much less impressive response when serotonin was injected into the VMN. The response to injections of tryptophan in both the VMN and PVN was similar to those seen with serotonin. When serotonin or tryptophan were injected into the PVN and VMN simultaneously, there was a synergistic increase in sympathetic firing rate. These data are consistent with the hypothesis that both norepinephrine and serotonin can modulate sympathetic firing rate through interaction with neurons in either the VMN or PVN.