A hypercaloric load induces thermogenesis but inhibits stress responses in the SNS and HPA system

1997 ◽  
Vol 272 (3) ◽  
pp. R840-R848 ◽  
Author(s):  
A. M. Strack ◽  
S. F. Akana ◽  
C. J. Horsley ◽  
M. F. Dallman

Caloric overingestion generates a sympathetic nervous system (SNS)-mediated increase in brown adipose tissue (BAT) thermogenesis; its effect on the hypothalamo-pituitary-adrenal (HPA) axis is unknown. To determine whether metabolic activation affects the HPA axis, male rats were provided palatable sucrose ad libitum. After 5 or 10 days of sucrose ingestion, BAT and basal and restraint-induced HPA variables were measured. Some rats were instrumented with temperature probes. BAT temperature and HPA axis responses to restraint were measured. Although caloric intake increased > or = 18%, body weight gain did not change after sucrose ingestion; DNA, protein, and uncoupling protein increased in BAT depots, and white adipose tissues were heavier after both 5 and 10 days. During days 5-10, the BAT-core temperature difference was +0.30 degrees C in sucrose rats and -0.46 degrees C in controls (P < 0.05); this, together with the biochemical changes, shows persistent activation of BAT by excess calories. Basal HPA measures were not altered. The sucrose group exhibited smaller BAT temperature and HPA responses to restraint on day 10; there was no HPA difference on day 5. We conclude that calorically mediated increases in BAT thermogenesis are independent of basal HPA activity; however, both systems respond concordantly to restraint stress. The diminished response to restraint in both systems in sucrose-fed rats may result from signals indicating increased energy stores.

Endocrinology ◽  
2005 ◽  
Vol 146 (5) ◽  
pp. 2193-2199 ◽  
Author(s):  
Susanne E. la Fleur ◽  
Hani Houshyar ◽  
Monica Roy ◽  
Mary F. Dallman

Abstract Although rats given the choice of eating high-density calories as concentrated sucrose solutions or lard exhibit reduced responsivity in the hypothalamo-pituitary-adrenal axis, rats fed high-fat diets have normal or augmented responses to stressors. To resolve this apparent discrepancy, we compared in adult male rats the effects of 7-d feeding with lard + chow (choice) to feeding a 50% lard-chow mixture (no-choice) and to chow only. Rats with choice composed diets with 50–60% total calories from lard. Rats were exposed to 30 min of restraint on d 7. In the choice group, there was a robust inhibition of ACTH and corticosterone responses to restraint compared with chow or no-choice groups. Total caloric intake was less with choice than no-choice. Fat depot weights and body weight gain were similar in the high-fat groups. Leptin concentrations were equal but insulin was higher in the choice group. We conclude the following: 1) choice of eating high-density calories strongly damps hypothalamo-pituitary-adrenal responses to stress; without choice, high-density diet is ineffective; and 2) insulin may signal metabolic well-being, and may act through hypothalamic sites to reduce caloric intake but through forebrain sites to damp stress responses.


2005 ◽  
Vol 289 (1) ◽  
pp. E15-E22 ◽  
Author(s):  
A. Valle ◽  
A. Català-Niell ◽  
B. Colom ◽  
F. J. García-Palmer ◽  
J. Oliver ◽  
...  

Sex-related differences in energy balance were studied in young Wistar rats fed standard chow pellets either ad libitum or in restricted amounts (60% of ad libitum intake) for 100 days. Caloric intake, indirect calorimetry, organ and adipose tissue weights, energy efficiency, liver mitochondrial respiration rate, and brown adipose tissue (BAT) uncoupling protein-1 (UCP1) content were measured. Ad libitum-fed females showed greater oxygen consumption (V̇o2) and carbon dioxide production (V̇co2) and lower energy efficiency than males. Caloric restriction induced a chronic drop of V̇o2 and V̇co2 in females but not in males over the period studied. Restricted females showed a better conservation of metabolic active organ mass and a greater decrease in adipose depots than restricted males. Moreover, changes of BAT size and UCP1 content suggest that BAT may be the main cause responsible for sex differences in the response of energy balance to caloric restriction. In conclusion, our results indicate that females under caloric restriction conditions deactivate facultative thermogenesis to a greater degree than males. This ability may have obvious advantages for female survival and therefore the survival of the species when food is limiting.


2003 ◽  
Vol 284 (5) ◽  
pp. E940-E945 ◽  
Author(s):  
Masahiko Ito ◽  
Akira Gomori ◽  
Akane Ishihara ◽  
Zenjun Oda ◽  
Satoshi Mashiko ◽  
...  

Melanin-concentrating hormone (MCH) is a cyclic orexigenic peptide expressed in the lateral hypothalamus. Recently, we demonstrated that chronic intracerebroventricular infusion of MCH induced obesity accompanied by sustained hyperphagia in mice. Here, we analyzed the mechanism of MCH-induced obesity by comparing animals fed ad libitum with pair-fed and control animals. Chronic infusion of MCH significantly increased food intake, body weight, white adipose tissue (WAT) mass, and liver mass in ad libitum-fed mice on a moderately high-fat diet. In addition, a significant increase in lipogenic activity was observed in the WAT of the ad libitum-fed group. Although body weight gain was marginal in the pair-fed group, MCH infusion clearly enhanced the lipogenic activity in liver and WAT. Plasma leptin levels were also increased in the pair-fed group. Furthermore, MCH infusion significantly reduced rectal temperatures in the pair-fed group. In support of these findings, mRNA expression of uncoupling protein-1, acyl-CoA oxidase, and carnitine palmitoyltransferase I, which are key molecules involved in thermogenesis and fatty acid oxidation, were reduced in the brown adipose tissue (BAT) of the pair-fed group, suggesting that MCH infusion might reduce BAT functions. We conclude that the activation of MCH neuronal pathways stimulated adiposity, in part resulting from increased lipogenesis in liver and WAT and reduced energy expenditure in BAT. These findings confirm that modulation of energy homeostasis by MCH may play a critical role in the development of obesity.


2021 ◽  
Author(s):  
Sebastian Dieckmann ◽  
Akim Strohmeyer ◽  
Monja Willershaeuser ◽  
Stefanie Maurer ◽  
Wolfgang Wurst ◽  
...  

Objective Activation of uncoupling protein 1 (UCP1) in brown adipose tissue (BAT) upon cold stimulation leads to substantial increase in energy expenditure to defend body temperature. Increases in energy expenditure after a high caloric food intake, termed diet-induced thermogenesis, are also attributed to BAT. These properties render BAT a potential target to combat diet-induced obesity. However, studies investigating the role of UCP1 to protect against diet-induced obesity are controversial and rely on the phenotyping of a single constitutive UCP1-knockout model. To address this issue, we generated a novel UCP1-knockout model by Cre-mediated deletion of Exon 2 in the UCP1 gene. We studied the effect of constitutive UCP1 knockout on metabolism and the development of diet-induced obesity. Methods UCP1 knockout and wildtype mice were housed at 30°C and fed a control diet for 4-weeks followed by 8-weeks of high-fat diet. Body weight and food intake were monitored continuously over the course of the study and indirect calorimetry was used to determine energy expenditure during both feeding periods. Results Based on Western blot analysis, thermal imaging and noradrenaline test, we confirmed the lack of functional UCP1 in knockout mice. However, body weight gain, food intake and energy expenditure were not affected by deletion of UCP1 gene function during both feeding periods. Conclusion Conclusively, we show that UCP1 does not protect against diet-induced obesity at thermoneutrality. Further we introduce a novel UCP1-KO mouse enabling the generation of conditional UCP1-knockout mice to scrutinize the contribution of UCP1 to energy metabolism in different cell types or life stages.


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.


1988 ◽  
Vol 255 (4) ◽  
pp. R616-R621 ◽  
Author(s):  
J. O. Hill ◽  
J. C. Anderson ◽  
D. Lin ◽  
F. Yakubu

The effects of differences in meal frequency on body weight, body composition, and energy expenditure were studied in mildly food-restricted male rats. Two groups were fed approximately 80% of usual food intake (as periodically determined in a group of ad libitum fed controls) for 131 days. One group received all of its food in 2 meals/day and the other received all of its food in 10-12 meals/day. The two groups did not differ in food intake, body weight, body composition, food efficiency (carcass energy gain per amount of food eaten), or energy expenditure at any time during the study. Both food-restricted groups had a lower food intake, body weight gain, and energy expenditure than a group of ad libitum-fed controls. In conclusion, these results suggest that amount of food eaten, but not the pattern with which it is ingested, has a major influence on energy balance during mild food restriction.


1995 ◽  
Vol 268 (4) ◽  
pp. C952-C957 ◽  
Author(s):  
J. Yannariello-Brown ◽  
S. H. Chapman ◽  
W. F. Ward ◽  
T. C. Pappas ◽  
P. H. Weigel

Circulating hyaluronan (HA) levels were investigated as a function of age and diet in Fischer 344 male rats. A biphasic pattern of age-related changes was observed in rats fed ad libitum a diet in which the protein source was soya/fish meal. HA levels in 3- to 6- and 22- to 29-mo-old rats were not statistically different. However, HA levels in 12- to 20-mo-old rats were 10-29% of the levels in younger or aged adults. HA levels were also measured in rats fed ad libitum a semisynthetic diet in which the protein source was hydrolyzed casein. Whereas the two colonies exhibited similar biphasic age-related changes, HA levels differed 4- to 20-fold at every age examined. Caloric restriction affected HA levels in 19-mo-old casein-fed rats; HA levels were 2.3 times higher than age-matched controls and were not statistically different from young or aged animals. Serum and plasma HA levels were identical in the same individuals at all ages tested. These data suggest that HA turnover and metabolism in the rat are affected by age, dietary composition, and caloric intake.


Endocrinology ◽  
2014 ◽  
Vol 155 (9) ◽  
pp. 3448-3458 ◽  
Author(s):  
Boris Monge-Roffarello ◽  
Sebastien M. Labbe ◽  
Marie-Claude Roy ◽  
Marie-Laurence Lemay ◽  
Estelle Coneggo ◽  
...  

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.


1987 ◽  
Vol 7 (2) ◽  
pp. 121-127 ◽  
Author(s):  
Nigel J. Fuller ◽  
Dorothy M. Stirling ◽  
Stephen Dunnett ◽  
Gavin P. Reynolds ◽  
Margaret Ashwell

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.


Sign in / Sign up

Export Citation Format

Share Document