Physiology of transgenic mice with brown fat ablation: obesity is due to lowered body temperature

1998 ◽  
Vol 274 (2) ◽  
pp. R287-R293 ◽  
Author(s):  
Susanne Klaus ◽  
Heike Münzberg ◽  
Christiane Trüloff ◽  
Gerhard Heldmaier
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Transgenic Mice ◽  
Uncoupling Protein ◽  
Core Body Temperature ◽  
Physiological Basis ◽  
Brown Adipose ◽  
Temperature Levels ◽  
Food Assimilation

We investigated the physiological basis for development of obesity in uncoupling protein-diphtheria toxin A chain (UCP-DTA) transgenic mice. In these mice the promoter of the brown adipose tissue (BAT)-specific UCP was used to drive expression of DTA, resulting in decreased BAT function and development of obesity and insulin resistance (Lowell, B. B., S. V. Susulic, A. Hamann, J. A. Lawitts, J. Himms-Hagen, B. B. Boyer, L. Kozak, and J. S. Flier. Nature 366: 740–742, 1994). In adult UCP-DTA mice, we measured food intake and food assimilation, locomotor activity, metabolic rate, and body temperature in comparison to control animals. No differences could be observed in food intake or assimilation and locomotor activity. Weight-specific metabolic rates at temperatures between 20 and 37°C, however, were consistently lower in transgenic mice. Continuous telemetric recording of core body temperature showed that transgenic mice displayed a downshift in body temperature levels of ∼0.9°C. In summary, we provide evidence that attenuated body temperature levels alone can be responsible for development of obesity and that BAT thermogenesis is a major determinant of body temperature levels in rodents.

scholarly journals Food Intake and Core Body Temperature of Pups and Adults in a db Mouse Line Deficient in the Long Form of the Leptin Receptor without Misty Mutation

2018 ◽  
Vol 2018 ◽  
pp. 1-9 ◽  
Author(s):  
Wijang Pralampita Pulong ◽  
Miharu Ushikai ◽  
Emi Arimura ◽  
Masaharu Abe ◽  
Hiroaki Kawaguchi ◽  
...  
Keyword(s):  
Food Intake ◽  
Body Temperature ◽  
Leptin Receptor ◽  
Uncoupling Protein ◽  
Core Body Temperature ◽  
Mrna Levels ◽  
Mouse Line ◽  
Brown Adipose ◽  
Long Form ◽  
Core Body

Different involvement of leptin signaling in food intake (FI) and body temperature (BT) in pups and adults has been suggested. However, the leptin receptor (Lepr) long-form-deficient (db) mouse line has not been fully examined in pups. In the most available db mouse line, wild-type (WT) mice have a mutation in the dedicator of cytokinesis 7 gene, named misty, which was recently revealed to be involved in neuronal development. Therefore, we established a line of db mice without the misty mutation using natural mating. Adult (8 weeks of age) homozygous db/db mice displayed significantly higher core body weight (BW) and FI and significantly lower core BT than WT mice. However, postnatal (2 weeks of age) db/db mice displayed similar BW and milk intake and significantly lower core BT than WT mice. Correspondingly, adult and postnatal db/db mice exhibited altered mRNA levels of hypothalamic orexigenic and anorexigenic peptide in adults but not in pups. Additionally, db/db mice displayed significantly lower mRNA levels of brown adipose tissue uncoupling protein 1 at both ages. In conclusion, the db mouse line without the misty mutation clearly showed the different involvements of the Lepr long form in FI and BT in pups and adults.

scholarly journals PGC-1β-expressing POMC neurons mediate the effect of leptin on thermoregulation in the mouse

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Julien Delezie ◽  
Jonathan F. Gill ◽  
Gesa Santos ◽  
Bettina Karrer-Cardel ◽  
Christoph Handschin
Keyword(s):  
Gene Expression ◽  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Heat Dissipation ◽  
Core Body Temperature ◽  
Locomotor Behavior ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
Brown Adipose

Abstract The arcuate nucleus (ARC) of the hypothalamus is a key regulator of food intake, brown adipose tissue (BAT) thermogenesis, and locomotor activity. Whole-body deficiency of the transcriptional coactivator peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1β (PGC-1β) disrupts mouse circadian locomotor activity and BAT-regulated thermogenesis, in association with altered gene expression at the central level. We examined whether PGC-1β expression in the ARC is required for proper energy balance and locomotor behavior by generating mice lacking the PGC-1β gene specifically in pro-opiomelanocortin (POMC) neurons. POMC neuron-specific deletion of PGC-1β did not impact locomotor behavior, food intake, body composition, energy fuel utilization and metabolic rate in fed, 24-h fasted and 24-h refed conditions. In contrast, in the fed state, deletion of PGC-1β in POMC cells elevated core body temperature during the nighttime period. Importantly, this higher body temperature is not associated with changes in BAT function and gene expression. Conversely, we provide evidence that mice lacking PGC-1β in POMC neurons are more sensitive to the effect of leptin on heat dissipation. Our data indicate that PGC-1β-expressing POMC neurons are part of a circuit controlling body temperature homeostasis and that PGC-1β function in these neurons is involved in the thermoregulatory effect of leptin.

scholarly journals Risperidone alters food intake, core body temperature, and locomotor activity in mice

2009 ◽  
Vol 96 (3) ◽  
pp. 457-463 ◽  
Author(s):  
Mark B. Cope ◽  
Xingsheng Li ◽  
Patricia Jumbo-Lucioni ◽  
Catherine A. DiCostanzo ◽  
Wendi G. Jamison ◽  
...  
Keyword(s):  
Locomotor Activity ◽  
Food Intake ◽  
Body Temperature ◽  
Core Body Temperature ◽  
Core Body

scholarly journals A refined method to monitor arousal from hibernation in the European hamster

2021 ◽  
Vol 17 (1) ◽  
Author(s):  
Fredrik A. F. Markussen ◽  
Vebjørn J. Melum ◽  
Béatrice Bothorel ◽  
David G. Hazlerigg ◽  
Valérie Simonneaux ◽  
...  
Keyword(s):  
Body Temperature ◽  
Core Body Temperature ◽  
Behavioural Adaptation ◽  
Ventilation Frequency ◽  
Reduced Body ◽  
Brown Adipose ◽  
Invasive Method ◽  
Warming Rate ◽  
Core Body ◽  
Environmental Temperatures

Abstract Background Hibernation is a physiological and behavioural adaptation that permits survival during periods of reduced food availability and extreme environmental temperatures. This is achieved through cycles of metabolic depression and reduced body temperature (torpor) and rewarming (arousal). Rewarming from torpor is achieved through the activation of brown adipose tissue (BAT) associated with a rapid increase in ventilation frequency. Here, we studied the rate of rewarming in the European hamster (Cricetus cricetus) by measuring both BAT temperature, core body temperature and ventilation frequency. Results Temperature was monitored in parallel in the BAT (IPTT tags) and peritoneal cavity (iButtons) during hibernation torpor-arousal cycling. We found that increases in brown fat temperature preceded core body temperature rises by approximately 48 min, with a maximum re-warming rate of 20.9℃*h-1. Re-warming was accompanied by a significant increase in ventilation frequency. The rate of rewarming was slowed by the presence of a spontaneous thoracic mass in one of our animals. Core body temperature re-warming was reduced by 6.2℃*h-1 and BAT rewarming by 12℃*h-1. Ventilation frequency was increased by 77% during re-warming in the affected animal compared to a healthy animal. Inspection of the position and size of the mass indicated it was obstructing the lungs and heart. Conclusions We have used a minimally invasive method to monitor BAT temperature during arousal from hibernation illustrating BAT re-warming significantly precedes core body temperature re-warming, informing future study design on arousal from hibernation. We also showed compromised re-warming from hibernation in an animal with a mass obstructing the lungs and heart, likely leading to inefficient ventilation and circulation.

scholarly journals Susceptibility to diet induced obesity at thermoneutral conditions is independent of UCP1

2021 ◽  
Author(s):  
Sebastian Dieckmann ◽  
Akim Strohmeyer ◽  
Monja Willershaeuser ◽  
Stefanie Maurer ◽  
Wolfgang Wurst ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Knockout Mice ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Exon 2 ◽  
Diet Induced Obesity ◽  
Brown Adipose ◽  
Knockout Model

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.

scholarly journals Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

2020 ◽  
Author(s):  
Xuemei Liu ◽  
Xiyu Feng ◽  
Chao Deng ◽  
Lu Liu ◽  
Yanping Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Olanzapine Treatment ◽  
Brown Adipose

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.

scholarly journals Brown adipose tissue activity is modulated in olanzapine-treated young rats by simvastatin

2020 ◽  
Author(s):  
Xuemei Liu ◽  
Xiyu Feng ◽  
Chao Deng ◽  
Lu Liu ◽  
Yanping Zeng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Food Intake ◽  
Brown Adipose Tissue ◽  
Body Weight Gain ◽  
Uncoupling Protein ◽  
Peroxisome Proliferator ◽  
Sprague Dawley ◽  
Olanzapine Treatment ◽  
Brown Adipose

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.

scholarly journals Impaired Thermogenesis and a Molecular Signature for Brown Adipose Tissue inId2Null Mice

2016 ◽  
Vol 2016 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Zhou ◽  
Maricela Robles-Murguia ◽  
Deepa Mathew ◽  
Giles E. Duffield
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Core Body Temperature ◽  
Specific Pattern ◽  
Molecular Signature ◽  
Brown Adipose ◽  
Core Body ◽  
The Impact

Inhibitor of DNA binding 2 (ID2) is a helix-loop-helix transcriptional repressor rhythmically expressed in many adult tissues. Our previous studies have demonstrated thatId2null mice have sex-specific elevated glucose uptake in brown adipose tissue (BAT). Here we further explored the role ofId2in the regulation of core body temperature over the circadian cycle and the impact ofId2deficiency on genes involved in insulin signaling and adipogenesis in BAT. We discovered a reduced core body temperature inId2−/− mice. Moreover, inId2−/− BAT, 30 genes includingIrs1,PPARs, andPGC-1s were identified as differentially expressed in a sex-specific pattern. These data provide valuable insights into the impact ofId2deficiency on energy homeostasis of mice in a sex-specific manner.

scholarly journals Regulatory effects of brown adipose tissue thermogenesis on maternal metabolic adaptation, placental efficiency, and fetal growth in mice

2018 ◽  
Vol 315 (6) ◽  
pp. E1224-E1231 ◽  
Author(s):  
Liping Qiao ◽  
Samuel Lee ◽  
Amanda Nguyen ◽  
William W. Hay ◽  
Jianhua Shao
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Brown Adipose Tissue ◽  
Fetal Growth ◽  
Core Body Temperature ◽  
Metabolic Adaptation ◽  
Glucose Transporter 1 ◽  
Brown Adipose ◽  
Placental Efficiency ◽  
Core Body

To determine the role of UCP1-mediated thermogenesis in controlling maternal metabolic adaptation to pregnancy, energy metabolism of C57BL/6 wild-type (WT) and Ucp1 gene knockout ( Ucp1−/−) mice was studied during pregnancy. With the progression of pregnancy, maternal energy expenditure rates (EERs), expression of UCP1, and core body temperature steadily declined in WT dams. Despite no significant alterations in core body temperature and weight gain during pregnancy, Ucp1−/− dams exhibited lower rates in EER decline. High-fat (HF) feeding not only robustly increased maternal UCP1 expression and core body temperature but also abolished gestation-suppressed EER in WT dams. However, HF-increased EERs were significantly attenuated in Ucp1−/− dams. Significantly increased fetal body weights and fetal/placental weight ratio were detected in fetuses from Ucp1−/− dams compared with fetuses from WT dams. Markedly increased expression levels of glucose transporter 1 and amino acid transporters were also observed in placentas from Ucp1−/− dams. Furthermore, blood glucose concentrations of fetuses from Ucp1−/− dams were significantly higher than those of fetuses from WT dams, indicating that maternal UCP1 has an inhibitory effect on placental efficiency and fetal growth. Taken all together, this study demonstrated that maternal brown adipose tissue plays an important role in controlling maternal metabolic adaptation and placental nutrient transport.

scholarly journals Circulation and metabolic rates in a natural hibernator: an integrative physiological model

2010 ◽  
Vol 299 (6) ◽  
pp. R1478-R1488 ◽  
Author(s):  
Marshall Hampton ◽  
Bethany T. Nelson ◽  
Matthew T. Andrews
Keyword(s):  
Body Temperature ◽  
Metabolic Rate ◽  
Core Body Temperature ◽  
Circulatory System ◽  
Physiological Model ◽  
Ground Squirrels ◽  
Metabolic Rates ◽  
Spermophilus Tridecemlineatus ◽  
Brown Adipose ◽  
Core Body

Small hibernating mammals show regular oscillations in their heart rate and body temperature throughout the winter. Long periods of torpor are abruptly interrupted by arousals with heart rates that rapidly increase from 5 beats/min to over 400 beats/min and body temperatures that increase by ∼30°C only to drop back into the hypothermic torpid state within hours. Surgically implanted transmitters were used to obtain high-resolution electrocardiogram and body temperature data from hibernating thirteen-lined ground squirrels ( Spermophilus tridecemlineatus ). These data were used to construct a model of the circulatory system to gain greater understanding of these rapid and extreme changes in physiology. Our model provides estimates of metabolic rates during the torpor-arousal cycles in different model compartments that would be difficult to measure directly. In the compartment that models the more metabolically active tissues and organs (heart, brain, liver, and brown adipose tissue) the peak metabolic rate occurs at a core body temperature of 19°C approximately midway through an arousal. The peak metabolic rate of the active tissues is nine times the normothermic rate after the arousal is complete. For the overall metabolic rate in all tissues, the peak-to-resting ratio is five. This value is high for a rodent, which provides evidence for the hypothesis that the arousal from torpor is limited by the capabilities of the cardiovascular system.

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