scholarly journals Hypothalamic CB1 Cannabinoid Receptors Regulate Energy Balance in Mice

Endocrinology ◽  
2012 ◽  
Vol 153 (9) ◽  
pp. 4136-4143 ◽  
Author(s):  
Pierre Cardinal ◽  
Luigi Bellocchio ◽  
Samantha Clark ◽  
Astrid Cannich ◽  
Matthias Klugmann ◽  
...  
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Receptor Gene ◽  
Receptor Activation ◽  
Cb1 Receptor ◽  
Mrna Levels ◽  
Receptor Signaling ◽  
Brown Adipose ◽  
The Impact

Cannabinoid type 1 (CB1) receptor activation is generally considered a powerful orexigenic signal and inhibition of the endocannabinoid system is beneficial for the treatment of obesity and related metabolic diseases. The hypothalamus plays a critical role in regulating energy balance by modulating both food intake and energy expenditure. Although CB1 receptor signaling has been implicated in the modulation of both these mechanisms, a complete understanding of its role in the hypothalamus is still lacking. Here we combined a genetic approach with the use of adeno-associated viral vectors to delete the CB1 receptor gene in the adult mouse hypothalamus and assessed the impact of such manipulation on the regulation of energy balance. Viral-mediated deletion of the CB1 receptor gene in the hypothalamus led to the generation of Hyp-CB1-KO mice, which displayed an approximately 60% decrease in hypothalamic CB1 receptor mRNA levels. Hyp-CB1-KO mice maintained on a normocaloric, standard diet showed decreased body weight gain over time, which was associated with increased energy expenditure and elevated β3-adrenergic receptor and uncoupling protein-1 mRNA levels in the brown adipose tissue but, surprisingly, not to changes in food intake. Additionally, Hyp-CB1-KO mice were insensitive to the anorectic action of the hormone leptin (5 mg/kg) and displayed a time-dependent hypophagic response to the CB1 inverse agonist rimonabant (3 mg/kg). Altogether these findings suggest that hypothalamic CB1 receptor signaling is a key determinant of energy expenditure under basal conditions and reveal its specific role in conveying the effects of leptin and pharmacological CB1 receptor antagonism on food intake.

scholarly journals Murine neuronatin deficiency is associated with a hypervariable food intake and bimodal obesity

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Irene Cimino ◽  
Debra Rimmington ◽  
Y. C. Loraine Tung ◽  
Katherine Lawler ◽  
Pierre Larraufie ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Positive Energy ◽  
Chow Diet ◽  
Chromatin Regulator ◽  
Positive Energy Balance ◽  
The Impact ◽  
Deficient Mice

AbstractNeuronatin (Nnat) has previously been reported to be part of a network of imprinted genes downstream of the chromatin regulator Trim28. Disruption of Trim28 or of members of this network, including neuronatin, results in an unusual phenotype of a bimodal body weight. To better characterise this variability, we examined the key contributors to energy balance in Nnat+/−p mice that carry a paternal null allele and do not express Nnat. Consistent with our previous studies, Nnat deficient mice on chow diet displayed a bimodal body weight phenotype with more than 30% of Nnat+/−p mice developing obesity. In response to both a 45% high fat diet and exposure to thermoneutrality (30 °C) Nnat deficient mice maintained the hypervariable body weight phenotype. Within a calorimetry system, food intake in Nnat+/−p mice was hypervariable, with some mice consuming more than twice the intake seen in wild type littermates. A hyperphagic response was also seen in Nnat+/−p mice in a second, non-home cage environment. An expected correlation between body weight and energy expenditure was seen, but corrections for the effects of positive energy balance and body weight greatly diminished the effect of neuronatin deficiency on energy expenditure. Male and female Nnat+/−p mice displayed subtle distinctions in the degree of variance body weight phenotype and food intake and further sexual dimorphism was reflected in different patterns of hypothalamic gene expression in Nnat+/−p mice. Loss of the imprinted gene Nnat is associated with a highly variable food intake, with the impact of this phenotype varying between genetically identical individuals.

Effects of ovarian hormones on energy balance and brown adipose tissue thermogenesis

1986 ◽  
Vol 250 (2) ◽  
pp. R245-R249 ◽  
Author(s):  
D. Richard
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Energy Intake ◽  
Ovarian Hormones ◽  
Ovariectomized Rats ◽  
Brown Adipose ◽  
Brown Adipose Tissue Thermogenesis

This study was carried out to investigate the nutritional energetics of ovariectomized rats with or without ovarian hormone replacement. Rats were divided into five groups: 1) sham operated, 2) ovariectomized, 3) ovariectomized and treated with progesterone, 4) ovariectomized and treated with estradiol, or 5) ovariectomized and treated with estradiol and progesterone. After 36 days of treatment, energy contents of all five groups were determined together with energy content of food and feces. Brown adipose tissue thermogenesis was assessed through mitochondrial GDP binding assay. Results show that ovariectomy leads to a 16% increase in metabolizable energy intake. This increase was accompanied by a twofold increase in body energy gain. Progesterone did not further affect energy intake and gain in ovariectomized rats. However, increases in both food intake and energy gain were prevented by the estradiol replacement therapy. There was no difference in energy expenditure between sham-operated and ovariectomized rats in the absence of estradiol. In estradiol-treated animals, energy expenditure (kJ.kg body wt-0.75 . day-1) showed a slight increase. There was no difference in protein content of interscapular brown adipose tissue between all five groups. GDP binding was slightly reduced in ovariectomized estradiol-treated rats. It is concluded from this study that ovarian hormones produce their effects on energy balance mainly by altering food intake.

scholarly journals Cannabinoid Type 1 (CB1) Receptors on Sim1-Expressing Neurons Regulate Energy Expenditure in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 156 (2) ◽  
pp. 411-418 ◽  
Author(s):  
Pierre Cardinal ◽  
Luigi Bellocchio ◽  
Omar Guzmán-Quevedo ◽  
Caroline André ◽  
Samantha Clark ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Cb1 Receptor ◽  
Cb1 Receptors ◽  
High Fat ◽  
Brown Adipose

The paraventricular nucleus of the hypothalamus (PVN) regulates energy balance by modulating not only food intake, but also energy expenditure (EE) and brown adipose tissue thermogenesis. To test the hypothesis that cannabinoid type 1 (CB1) receptor in PVN neurons might control these processes, we used the Cre/loxP system to delete CB1 from single-minded 1 (Sim1) neurons, which account for the majority of PVN neurons. On standard chow, mice lacking CB1 receptor in Sim1 neurons (Sim1-CB1-knockout [KO]) had food intake, body weight, adiposity, glucose metabolism, and EE comparable with wild-type (WT) (Sim1-CB1-WT) littermates. However, maintenance on a high-fat diet revealed a gene-by-diet interaction whereby Sim1-CB1-KO mice had decreased adiposity, improved insulin sensitivity, and increased EE, whereas feeding behavior was similar to Sim1-CB1-WT mice. Additionally, high-fat diet-fed Sim1-CB1-KO mice had increased mRNA expression of the β3-adrenergic receptor, as well as of uncoupling protein-1, cytochrome-c oxidase subunit IV and mitochondrial transcription factor A in the brown adipose tissue, all molecular changes suggestive of increased thermogenesis. Pharmacological studies using β-blockers suggested that modulation of β-adrenergic transmission play an important role in determining EE changes observed in Sim1-CB1-KO. Finally, chemical sympathectomy abolished the obesity-resistant phenotype of Sim1-CB1-KO mice. Altogether, these findings reveal a diet-dependent dissociation in the CB1 receptor control of food intake and EE, likely mediated by the PVN, where CB1 receptors on Sim1-positive neurons do not impact food intake but hinder EE during dietary environmental challenges that promote body weight gain.

scholarly journals TrkB receptor signaling in the nucleus tractus solitarius mediates the food intake-suppressive effects of hindbrain BDNF and leptin

2012 ◽  
Vol 302 (10) ◽  
pp. E1252-E1260 ◽  
Author(s):  
Andrea M. Spaeth ◽  
Scott E. Kanoski ◽  
Matthew R. Hayes ◽  
Harvey J. Grill
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Receptor Antagonist ◽  
Nucleus Tractus Solitarius ◽  
Receptor Activation ◽  
Reduce Food Intake ◽  
Receptor Signaling ◽  
Inhibitory Effects ◽  
Trkb Receptor ◽  
Medial Nucleus

Brain-derived neurotrophic factor (BDNF) and TrkB receptor signaling contribute to the central nervous system (CNS) control of energy balance. The role of hindbrain BDNF/TrkB receptor signaling in energy balance regulation is examined here. Hindbrain ventricular BDNF suppressed body weight through reductions in overall food intake and meal size and by increasing core temperature. To localize the neurons mediating the energy balance effects of hindbrain ventricle-delivered BDNF, ventricle subthreshold doses were delivered directly to medial nucleus tractus solitarius (mNTS). mNTS BDNF administration reduced food intake significantly, and this effect was blocked by preadministration of a highly selective TrkB receptor antagonist {[N2–2-2-Oxoazepan-3-yl amino]carbonyl phenyl benzo (b)thiophene-2-carboxamide (ANA-12)}, suggesting that TrkB receptor activation mediates hindbrain BDNF's effect on food intake. Because both BDNF and leptin interact with melanocortin signaling to reduce food intake, we also examined whether the intake inhibitory effects of hindbrain leptin involve hindbrain-specific BDNF/TrkB activation. BDNF protein content within the dorsal vagal complex of the hindbrain was increased significantly by hindbrain leptin delivery. To assess if BDNF/TrkB receptor signaling acts downstream of leptin signaling in the control of energy balance, leptin and ANA-12 were coadministered into the mNTS. Administration of the TrkB receptor antagonist attenuated the intake-suppressive effects of leptin, suggesting that mNTS TrkB receptor activation contributes to the mediation of the anorexigenic effects of hindbrain leptin. Collectively, these results indicate that TrkB-mediated signaling in the mNTS negatively regulates food intake and, in part, the intake inhibitory effects of leptin administered into the NTS.

The role of exercise in thermogenesis and energy balance

1989 ◽  
Vol 67 (4) ◽  
pp. 402-409 ◽  
Author(s):  
Denis Richard ◽  
Serge Rivest
Keyword(s):  
Energy Balance ◽  
Food Intake ◽  
Energy Expenditure ◽  
Exercise Training ◽  
Female Rats ◽  
Male Rats ◽  
Brown Adipose ◽  
Term Energy

The role of exercise training in energy balance has been reviewed. Recent well-conducted studies showed that exercise may increase energy expenditure not only during the period of exercise itself but during the postexercise period as well. This notion of excess postexercise oxygen consumption (EPOC), which has been a controversial issue for many years, is now becoming a generally well-accepted concept, the consensus being that EPOC takes place following prolonged and strenuous exercise bouts. Besides, the role of EPOC in long-term energy balance remains to be determined. Long-term energy balance studies carried out in rats show that exercise affects energy balance by altering food intake and promoting energy expenditure. In male rats exercise causes a marked decrease in energy intake which contributes, in association with the expenditure of exercise itself, to retard lean and fat tissue growth. From the suppressed deposition of lean body mass, decreases in basal metabolic rate can be predicted in males. In female rats, exercise does not affect food intake; the lower energy gain of exercise-trained females results from the elevated expenditure rate associated with exercise itself. In both male and female rats, there is no evidence that exercise training affects energy expenditure other than during exercise itself unless the habitual feeding pattern of the rats is radically modified. The interactive effects of diet and exercise, which have to be further investigated in long-term energy balance, emerge as a promising area of research.Key words: exercise training, nutritional energetics, brown adipose tissue, diet-induced thermogenesis, body composition.

scholarly journals The effect of breakfast on appetite regulation, energy balance and exercise performance

2015 ◽  
Vol 75 (3) ◽  
pp. 319-327 ◽  
Author(s):  
David J. Clayton ◽  
Lewis J. James
Keyword(s):  
Energy Balance ◽  
Energy Expenditure ◽  
Energy Intake ◽  
Exercise Performance ◽  
Intervention Studies ◽  
Precise Determination ◽  
Positive Energy ◽  
Cross Sectional ◽  
Positive Energy Balance ◽  
The Impact

The belief that breakfast is the most important meal of day has been derived from cross-sectional studies that have associated breakfast consumption with a lower BMI. This suggests that breakfast omission either leads to an increase in energy intake or a reduction in energy expenditure over the remainder of the day, resulting in a state of positive energy balance. However, observational studies do not imply causality. A number of intervention studies have been conducted, enabling more precise determination of breakfast manipulation on indices of energy balance. This review will examine the results from these studies in adults, attempting to identify causal links between breakfast and energy balance, as well as determining whether consumption of breakfast influences exercise performance. Despite the associations in the literature, intervention studies have generally found a reduction in total daily energy intake when breakfast is omitted from the daily meal pattern. Moreover, whilst consumption of breakfast supresses appetite during the morning, this effect appears to be transient as the first meal consumed after breakfast seems to offset appetite to a similar extent, independent of breakfast. Whether breakfast affects energy expenditure is less clear. Whilst breakfast does not seem to affect basal metabolism, breakfast omission may reduce free-living physical activity and endurance exercise performance throughout the day. In conclusion, the available research suggests breakfast omission may influence energy expenditure more strongly than energy intake. Longer term intervention studies are required to confirm this relationship, and determine the impact of these variables on weight management.

Role of thermogenesis in the regulation of energy balance in relation to obesity

1989 ◽  
Vol 67 (4) ◽  
pp. 394-401 ◽  
Author(s):  
Jean Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Thermal Balance ◽  
Prominent Feature ◽  
Thermic Effect Of Food ◽  
Brown Adipose ◽  
Effect Of Food ◽  
Thermic Effect

Obligatory thermogenesis is a necessary accompaniment of all metabolic processes involved in maintenance of the body in the living state, and occurs in ail organs. It includes energy expenditure involved in ingesting, digesting, and processing food (thermic effect of food (TEF)). At certain life stages extra energy expenditure for growth, pregnancy, or lactation would also be obligatory. Facultative thermogenesis is superimposed on obligatory thermogenesis and can be rapidly switched on and rapidly suppressed by the nervous system. Facultative thermogenesis is important in both thermal balance, in which control of thermoregulatory thermogenesis (shivering in muscle, nonshivering in brown adipose tissue (BAT)) balances neural control of heat loss mechanisms, and in energy balance, in which control of facultative thermogenesis (exercise-induced in muscle, diet-induced thermogenesis (DIT) in BAT) balances control of energy intake. Thermal balance (i.e., body temperature) is much more stringently controlled than energy balance (i.e., body energy stores). Reduced energy expenditure for thermogenesis is important in two types of obesity in laboratory animals. In the first type, deficient DIT in BAT is a prominent feature of altered energy balance. It may or may not be associated with hyperphagia. In a second type, reduced cold-induced thermogenesis in BAT as well as in other organs is a prominent feature of altered thermal balance. This in turn results in altered energy balance and obesity, exacerbated in some examples by hyperphagia. In some of the hyperphagic obese animals it is likely that the exaggerated obligatory thermic effect of food so alters thermal balance that BAT thermogenesis is suppressed. In all obese animals, deficient hypothalamic control of facultative thermogenesis and (or) food intake is implicated.Key words: thermogenesis, brown adipose tissue, energy balance, obesity, cold, thermoregulation, diet.

scholarly journals Inactivation of the adrenergic receptor β2 disrupts glucose homeostasis in mice

2014 ◽  
Vol 221 (3) ◽  
pp. 381-390 ◽  
Author(s):  
Gustavo W Fernandes ◽  
Cintia B Ueta ◽  
Tatiane L Fonseca ◽  
Cecilia H A Gouveia ◽  
Carmen L Lancellotti ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Mrna Levels ◽  
High Fat ◽  
Adaptive Thermogenesis ◽  
Brown Adipose ◽  
Similar Body

Three types of beta adrenergic receptors (ARβ1–3) mediate the sympathetic activation of brown adipose tissue (BAT), the key thermogenic site for mice which is also present in adult humans. In this study, we evaluated adaptive thermogenesis and metabolic profile of a mouse withArβ2knockout (ARβ2KO). At room temperature, ARβ2KO mice have normal core temperature and, upon acute cold exposure (4 °C for 4 h), ARβ2KO mice accelerate energy expenditure normally and attempt to maintain body temperature. ARβ2KO mice also exhibited normal interscapular BAT thermal profiles during a 30-min infusion of norepinephrine or dobutamine, possibly due to marked elevation of interscapular BAT (iBAT) and ofArβ1, andArβ3mRNA levels. In addition, ARβ2KO mice exhibit similar body weight, adiposity, fasting plasma glucose, cholesterol, and triglycerides when compared with WT controls, but exhibit marked fasting hyperinsulinemia and elevation in hepaticPepck(Pck1) mRNA levels. The animals were fed a high-fat diet (40% fat) for 6 weeks, ARβ2KO mice doubled their caloric intake, accelerated energy expenditure, and inducedUcp1expression in a manner similar to WT controls, exhibiting a similar body weight gain and increase in the size of white adipocytes to the WT controls. However, ARβ2KO mice maintain fasting hyperglycemia as compared with WT controls despite very elevated insulin levels, but similar degrees of liver steatosis and hyperlipidemia. In conclusion, inactivation of the ARβ2KO pathway preserves cold- and diet-induced adaptive thermogenesis but disrupts glucose homeostasis possibly by accelerating hepatic glucose production and insulin secretion. Feeding on a high-fat diet worsens the metabolic imbalance, with significant fasting hyperglycemia but similar liver structure and lipid profile to the WT controls.

Energy intake and fur in summer- and winter-acclimated Siberian hamsters (Phodopus sungorus)

2001 ◽  
Vol 281 (2) ◽  
pp. R519-R527 ◽  
Author(s):  
Alexander S. Kauffman ◽  
Alessandra Cabrera ◽  
Irving Zucker
Keyword(s):  
Food Intake ◽  
Energy Intake ◽  
Ventral Surface ◽  
Phodopus Sungorus ◽  
Ambient Temperatures ◽  
Siberian Hamsters ◽  
Daily Food ◽  
Brown Adipose ◽  
Wide Range ◽  
The Impact

Few studies have directly addressed the impact of fur on seasonal changes in energy intake. The daily food intake of Siberian hamsters ( Phodopus sungorus) was measured under simulated summer and winter conditions in intact animals and those with varying amounts of pelage removed. Energy intake increased up to 44% above baseline control values for approximately 2–3 wk after complete shaving. Increases in food intake varied with condition and were greater in hamsters housed in short than long day lengths and at low (5°C) than moderate (23°C) ambient temperatures. Removal of 8 cm2 of dorsal fur, equivalent to 30% of the total dorsal fur surface, increased food intake, but removal of 4 cm2 had no effect. An 8-cm2 fur extirpation from the ventral surface did not increase food consumption. Food intake was not influenced differentially by fur removal from above brown adipose tissue hot spots. Fur plays a greater role in energy balance in winter- than summer-acclimated hamsters and conserves energy under a wide range of environmental conditions.

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.

Sign in / Sign up

Export Citation Format

Share Document