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

1997 ◽  
Vol 273 (2) ◽  
pp. R554-R559 ◽  
Author(s):  
M. Monda ◽  
A. Sullo ◽  
V. De Luca ◽  
M. P. Pellicano ◽  
A. Viggiano

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.

1996 ◽  
Vol 271 (6) ◽  
pp. R1638-R1642 ◽  
Author(s):  
M. Monda ◽  
A. Sullo ◽  
E. De Luca ◽  
M. P. Pellicano

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.


1993 ◽  
Vol 71 (8) ◽  
pp. 604-610 ◽  
Author(s):  
Q. Li ◽  
J. Thornhill

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.


1996 ◽  
Vol 270 (6) ◽  
pp. R1215-R1219 ◽  
Author(s):  
M. Monda ◽  
A. Papa ◽  
G. Brizzi ◽  
B. DeLuca

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.


1984 ◽  
Vol 247 (6) ◽  
pp. R979-R987 ◽  
Author(s):  
B. E. Levin ◽  
J. Triscari ◽  
E. Marquet ◽  
A. C. Sullivan

The effect of neonatal sympathectomy with guanethidine (50 mg/kg for 3 wk) on the development of diet-induced obesity (DIO) was assessed by raising guanethidine-(G) or saline-treated (S) Sprague-Dawley rats in small litters (4-5 pups/dam) and feeding a high-calorie diet from weaning (n = 29–30) or by raising similarly treated rats in normal litters (10 pups/dam) and feeding chow from weaning (n = 29–30). Sympathectomy depleted norepinephrine (NE) levels 65–98% in all organs except the adrenals and brain but had no statistically significant effect on weight gain, food intake, food efficiency, body composition, plasma glycerol, insulin, or glucose, or on basal rectal temperatures in either diet group; there was a tendency toward increased adiposity in sympathectomized rats. Despite 95–98% depletion of NE in interscapular brown adipose tissue (IBAT), sympathectomy affected only the percentage of multilocular cells that was decreased 46-69%. Rats from small litters in both treatment groups (S and G) became obese without increased food intake (increased food efficiency), had heavier IBAT pads with bigger cells and more lipid, and were also hyperlipidemic, hyperinsulinemic, and hyperglycemic compared with controls. Therefore neonatal sympathectomy was not as significant in the subsequent development of DIO as were diet and litter size.


1995 ◽  
Vol 268 (6) ◽  
pp. R1533-R1538 ◽  
Author(s):  
B. De Luca ◽  
M. Monda ◽  
A. Sullo

The effects of the inhibition of nitric oxide (NO) production on eating behavior and thermogenesis were evaluated in the present experiments. NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO production, was injected intraperitoneally or intracerebroventricularly, and food intake, oxygen consumption rate, and interscapular brown adipose tissue (BAT) temperature were evaluated in conscious rats. The firing rate of sympathetic nerves innervating interscapular BAT was recorded in urethan-anesthetized animals. L-NAME, intraperitoneally injected, decreased food intake, oxygen consumption, temperature, and firing rate of sympathetic nerves innervating interscapular BAT. Intracerebroventricular injection of L-NAME decreased food intake and enhanced oxygen consumption, temperature, and firing rate of sympathetic nerves innervating BAT. The latter changes were similar to those found after lateral hypothalamic lesions. The opposite changes in oxygen consumption, temperature, and sympathetic activity of BAT that followed L-NAME injection through the two different routes were probably due to different effects of the molecule on sympathetic output. Impaired brain production of NO, which followed intracerebroventricular L-NAME, directly increased sympathetic activity, whereas the same activity that followed intraperitoneal L-NAME was depressed by increased blood pressure, which was elicited by the impaired peripheral production of NO.


1988 ◽  
Vol 255 (3) ◽  
pp. R507-R512 ◽  
Author(s):  
T. Sakaguchi ◽  
M. Takahashi ◽  
G. A. Bray

Measurements of sympathetic firing rate have been made after the acute microinjection of glucose or insulin into the lateral hypothalamic area as well as after ablation of this area with locally injected gold thioglucose. Injection of glucose into the lateral hypothalamus (LH) produced a small but significant and dose-dependent reduction in the firing rate of efferent sympathetic nerves to interscapular brown adipose tissue. Injection of insulin into the same region produced a very short-lived increase in efferent sympathetic firing rate. Bilateral lesions in the lateral hypothalamus produced by microinjection and gold thioglucose lowered body weight more than sham injections into the LH of control animals. There was an increase in basal sympathetic firing rate at 3, 9, and 24 h after LH lesions. There was also an increase in firing rate at 1 and 3 days, but by 7 days firing rate had returned to control levels. The data support the hypothesis that LH lesions enhance sympathetic activity but show only very limited modulation by glucose or insulin.


2020 ◽  
Author(s):  
Xuemei Liu ◽  
Xiyu Feng ◽  
Chao Deng ◽  
Lu Liu ◽  
Yanping Zeng ◽  
...  

Abstract BackgroundPrescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant sedation, weight gain, and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.MethodsTo investigate the efficacy of interventions of statin aimed at reversing SGA-induced dyslipidemia, young Sprague Dawley (SD) rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks.ResultsOlanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but had no significant effect on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. A down-regulating of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) expression was observed in brown adipose tissue (BAT) in the olanzapine-only group, following a significant decrease in the ratio of phosphorylated PKA (p-PKA)/PKA. Interestingly, these protein changes could be reversed by co-treatment with O+B. Our results demonstrated simvastatin to be effective in ameliorating TC and TG elevated by olanzapine.ConclusionsModulation of BAT activity could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.


2020 ◽  
Author(s):  
Xuemei Liu ◽  
Xiyu Feng ◽  
Chao Deng ◽  
Lu Liu ◽  
Yanping Zeng ◽  
...  

Abstract Background Prescription of second-generation antipsychotic drugs (SGAs) to childhood/adolescent has exponentially increased in recent years, which was associated with the greater risk of significant weight gain and dyslipidemia. Statin is considered a potential preventive and treatment approach for reducing SGA-induced weight gain and dyslipidemia in schizophrenia patients. However, the effect of statin treatment in children and adolescents with SGA-induced dyslipidemia is not clearly demonstrated.Methods To investigate the efficacy of statin interventions for reversing SGA-induced dyslipidemia, young Sprague Dawley rats were treated orally with either olanzapine (1.0 mg/kg, t.i.d.), simvastatin (3.0 mg/kg, t.i.d.), olanzapine plus simvastatin (O+S), or vehicle (control) for 5 weeks. Results Olanzapine treatment increased weight gain, food intake and feeding efficiency compared to the control, while O+S co-treatment significantly reversed body weight gain but without significant effects on food intake. Moreover, olanzapine treatment induced a slight but significant reduction in body temperature, with a decrease in locomotor activity. Fasting plasma glucose, triglycerides (TG), and total cholesterol (TC) levels were markedly elevated in the olanzapine-only group, whereas O+S co-treatment significantly ameliorated these changes. Pronounced activation of lipogenic gene expression in the liver and down-regulated expression of uncoupling protein-1 (UCP1) and peroxisome-proliferator-activated receptor-γ co-activator-1α (PGC-1α) in brown adipose tissue (BAT) was observed in the olanzapine-only group. Interestingly, these protein changes could be reversed by co-treatment with O+B. Conclusions Simvastatin is effective in ameliorating TC and TG elevated by olanzapine. Modulation of BAT activity by statins could be a partial mechanism in reducing metabolic side effects caused by SGAs in child and adolescent patients.


1957 ◽  
Vol 35 (1) ◽  
pp. 31-37 ◽  
Author(s):  
D. G. Montemurro ◽  
J. A. F. Stevenson

With the use of the Horsley–Clarke stereotaxic instrument, bilateral electrolytic lesions were placed in the lateral hypothalamic areas of female Sprague–Dawley rats. Changes in food and water intake and body weight were correlated with the histological localization of the lesions. Rats with large lesions in the frontal plane of the middle of the tuber cinereum died within a week of the operation. Food and water administered by stomach tube did not prevent weight loss and death.Two rats developed adipsia which lasted 13 and 16 days respectively; 10 ml. of tap water per day by stomach tube resulted in increases in food intake and body weight during the period of adipsia. These rats had lesions in the lateral hypothalamic areas in the frontal plane of the middle of the tuber cinereum, but these were small and relatively asymmetrical.Another rat refused water from the time of operation until sacrifice (55 days). Administration of 20 ml. per day of tap water caused an increase in food intake and body weight, and a general improvement. Whenever intake of water was not imposed by stomach tube, however, the food intake dropped and body weight was lost. This animal failed to drink spontaneously. The lesions in this animal were more symmetrical, slightly more dorsal, and about 0.75 mm. more posterior than those which produced temporary adipsia. In the rat, an area essential to the regulation of voluntary consumption of water appears to be located in the lateral hypothalamic areas at about the plane of the posterior ventromedial nuclei and the anterior border of the premammillary nuclei.


Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 796 ◽  
Author(s):  
Andrea Gille ◽  
Bojan Stojnic ◽  
Felix Derwenskus ◽  
Andreas Trautmann ◽  
Ulrike Schmid-Staiger ◽  
...  

Phaeodactylum tricornutum (P. tricornutum) comprise several lipophilic constituents with proposed anti-obesity and anti-diabetic properties. We investigated the effect of an ethanolic P. tricornutum extract (PTE) on energy metabolism in obesity-prone mice fed a high fat diet (HFD). Six- to eight-week-old male C57BL/6J mice were switched to HFD and, at the same time, received orally placebo or PTE (100 mg or 300 mg/kg body weight/day). Body weight, body composition, and food intake were monitored. After 26 days, blood and tissue samples were collected for biochemical, morphological, and gene expression analyses. PTE-supplemented mice accumulated fucoxanthin metabolites in adipose tissues and attained lower body weight gain, body fat content, weight of white adipose tissue (WAT) depots, and inguinal WAT adipocyte size than controls, independent of decreased food intake. PTE supplementation was associated with lower expression of Mest (a marker of fat tissue expandability) in WAT depots, lower gene expression related to lipid uptake and turnover in visceral WAT, increased expression of genes key to fatty acid oxidation and thermogenesis (Cpt1, Ucp1) in subcutaneous WAT, and signs of thermogenic activation including enhanced UCP1 protein in interscapular brown adipose tissue. In conclusion, these data show the potential of PTE to ameliorate HFD-induced obesity in vivo.


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