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.

Ventromedial hypothalamic knife-cut lesions in rats resistant to dietary obesity

1984 ◽  
Vol 246 (6) ◽  
pp. R943-R948 ◽  
Author(s):  
J. Oku ◽  
G. A. Bray ◽  
J. S. Fisler ◽  
R. Schemmel
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
High Fat Diet ◽  
Corn Oil ◽  
High Fat ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose ◽  
Dietary Obesity

The effects of ventromedial hypothalamic (VMH) knife-cut lesions on food intake and body weight of S 5B/Pl rats, which are normally resistant to obesity when eating a high-fat diet, were examined in two experiments. In the first experiment body weight increased only slightly after VMH knife-cut lesions when animals were fed pelleted laboratory chow or a 10% corn oil diet. When eating the 30% corn oil diet, however, body weight increased in the VMH knife-cut rats. In the second experiment VMH knife-cut lesions produced a small weight gain in rats fed the 10% fat diet; this manipulation also increased food intake and disrupted the normal diurnal feeding pattern. Changes in the weight of the liver, interscapular brown adipose tissue, and white adipose tissue paralleled the changes in body weight. Plasma insulin increased in the rats eating the 30% corn oil diet ad libitum but not in the VMH-lesioned animals pair fed to the sham-operated rats. Incorporation of 3H from 3H2O into lipid was significantly increased in white fat of animals with VMH knife cuts. Similar results were obtained from incubation of adipose tissue in vitro with insulin and radioactively labeled glucose. These studies show that hypothalamic knife-cut lesions can remove the resistance of the S 5B/Pl rats to obesity when they are fed a high-fat diet.

scholarly journals AgRP Neuron-Specific Deletion of Glucocorticoid Receptor Leads to Increased Energy Expenditure and Decreased Body Weight in Female Mice on a High-Fat Diet

Endocrinology ◽  
2016 ◽  
Vol 157 (4) ◽  
pp. 1457-1466 ◽  
Author(s):  
Miyuki Shibata ◽  
Ryoichi Banno ◽  
Mariko Sugiyama ◽  
Takashi Tominaga ◽  
Takeshi Onoue ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Energy Expenditure ◽  
Glucocorticoid Receptor ◽  
High Fat Diet ◽  
Uncoupling Protein ◽  
Chow Diet ◽  
Wild Type ◽  
High Fat ◽  
Brown Adipose

Abstract Agouti-related protein (AgRP) expressed in the arcuate nucleus is a potent orexigenic neuropeptide, which increases food intake and reduces energy expenditure resulting in increases in body weight (BW). Glucocorticoids, key hormones that regulate energy balance, have been shown in rodents to regulate the expression of AgRP. In this study, we generated AgRP-specific glucocorticoid receptor (GR)-deficient (knockout [KO]) mice. Female and male KO mice on a high-fat diet (HFD) showed decreases in BW at the age of 6 weeks compared with wild-type mice, and the differences remained significant until 16 weeks old. The degree of resistance to diet-induced obesity was more robust in female than in male mice. On a chow diet, the female KO mice showed slightly but significantly attenuated weight gain compared with wild-type mice after 11 weeks, whereas there were no significant differences in BW in males between genotypes. Visceral fat pad mass was significantly decreased in female KO mice on HFD, whereas there were no significant differences in lean body mass between genotypes. Although food intake was similar between genotypes, oxygen consumption was significantly increased in female KO mice on HFD. In addition, the uncoupling protein-1 expression in the brown adipose tissues was increased in KO mice. These data demonstrate that the absence of GR signaling in AgRP neurons resulted in increases in energy expenditure accompanied by decreases in adiposity in mice fed HFD, indicating that GR signaling in AgRP neurons suppresses energy expenditure under HFD conditions.

scholarly journals Low-dose UV radiation before running wheel access activates brown adipose tissue

2020 ◽  
Vol 244 (3) ◽  
pp. 473-486 ◽  
Author(s):  
Tristan S Allemann ◽  
Gursimran K Dhamrait ◽  
Naomi J Fleury ◽  
Tamara N Abel ◽  
Prue H Hart ◽  
...  
Keyword(s):  
Physical Activity ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
High Fat Diet ◽  
Low Dose ◽  
High Fat ◽  
Running Wheel ◽  
Brown Adipose ◽  
Running Wheels

In previous preclinical studies, low (non-burning) doses of UV radiation (UVR) limited weight gain and metabolic dysfunction in mice fed with a high-fat diet. Here, we explored the effects of low-dose UVR on physical activity and food intake and mechanistic pathways in interscapular brown adipose tissue (iBAT). Young adult C57Bl/6J male mice, housed as individuals, were fed a high-fat diet and exposed to low-dose UVR (sub-oedemal, 1 kJ/m2 UVB, twice-a-week) or ‘mock’ treatment, with or without running wheel access (2 h, for ‘moderate’ physical activity) immediately after phototherapy. There was no difference in distance run in mice exposed to UVR or mock-treated over 12 weeks of exposure to running wheels (P = 0.14). UVR (alone) did not significantly affect food intake, adiposity, or signs of glucose dysfunction. Access to running wheels increased food intake (after 10 weeks, P ≤ 0.02) and reduced gonadal white adipose tissue and iBAT mass (P ≤ 0.03). Body weight and hepatic steatosis were lowest in mice exposed to UVR with running wheel access. In the iBAT of mice exposed to UVR and running wheels, elevated Atgl, Cd36, Fasn, Igf1, Pparγ, and Ucp1 mRNAs and reduced CD11c on F4-80 + MHC class II+ macrophages were observed, while renal Sglt2 mRNA levels were increased, compared to high-fat diet alone (P ≤ 0.03). Blood levels of 25-hydroxyvitamin D were not increased by exposure to UVR and/or access to running wheels. In conclusion, when combined with physical activity, low-dose UVR may more effectively limit adiposity (specifically, body weight and hepatic steatosis) and modulate metabolic and immune pathways in iBAT.

scholarly journals Single Head-Neck Irradiation Intervention Increases Thyroid Hormone Level and Enhances Energy Metabolism in High-Fat Diet Mice

2020 ◽  
Author(s):  
Qian Lin ◽  
Caishun Zhang ◽  
Manwen Li ◽  
Haidan Wang ◽  
Kaizhen Su ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Metabolism ◽  
Food Intake ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Brown Adipose ◽  
Neck Irradiation ◽  
Head Neck

Abstract Radiotherapy, an established treatment of malignant diseases of the head and neck, increases the risk of chronic metabolic disorders. However, the molecular mechanisms responsible for metabolic dysfunction after irradiation remain unknown. We aimed to determine whether single head-neck irradiation intervention changes the levels of thyroid hormones and affects energy metabolism in high-fat diet mice and in chow diet mice. C57BL/6 mice were treated with a single dose of 6 Gy X-ray head-neck irradiation and were fed a high-fat diet. Body weight, accumulated food intake, fasting blood glucose and glucose tolerance were measured during the study. Plasma, brown adipose tissue, thyroid, liver and white adipose tissue were collected for histological analysis. We found that head-neck irradiation significantly increased food intake and decreased body weight in high-fat diet mice. However, there were no obvious changes in chow diet mice. Further studies showed that head-neck irradiation significantly increased levels of 3,5,3’-triiodothyronine and thyroid-stimulating hormone, as well as expression of uncoupling protein 1 in brown adipose tissue and glucose transporter 2 in liver in high-fat diet mice. Our results suggest that single head-neck irradiation intervention increases thyroid hormones levels and enhances energy metabolism in high-fat diet mice.

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.

Early dietary intervention: long-term effects on blood pressure, brain neuropeptide Y, and adiposity markers

2005 ◽  
Vol 288 (6) ◽  
pp. E1236-E1243 ◽  
Author(s):  
Elena Velkoska ◽  
Timothy J. Cole ◽  
Margaret J. Morris
Keyword(s):  
Blood Pressure ◽  
Body Weight ◽  
Adipose Tissue ◽  
Neuropeptide Y ◽  
Litter Size ◽  
High Fat Diet ◽  
Dietary Intervention ◽  
High Fat ◽  
Brown Adipose

Early life nutrition impacts on subsequent risk of obesity and hypertension. Several brain chemicals responsible for both feeding and cardiovascular regulation are altered in obesity. We examined effects of early postnatal overnutrition on blood pressure, brain neuropeptide Y (NPY), and adiposity markers. Rat pup litters were adjusted to either 3 or 12 male animals (overnutrition and control, respectively) on day 1 of life. After weaning, rats were given either a palatable high-fat diet or standard chow. Smaller litter pups were significantly heavier by 17 days of age. By 16 wk, the effect of litter size was masked by that of diet, postweaning. Small and normal litter animals fed a high-fat diet had similar increases in body weight, plasma insulin, leptin, and adiponectin concentrations, leptin mRNA, and fat masses relative to chow-fed animals. An increase in 11β-hydroxysteroid dehydrogenase-1 mRNA in white adipose tissue, and a decrease in uncoupling protein-1 mRNA in brown adipose tissue in both small litter groups at 16 wk of age, may represent a programming effect of the altered litter size. NPY concentration in the paraventricular nucleus of the hypothalamus was reduced in high fat-fed groups. Blood pressure was significantly elevated at 13 wk in high-fat-fed animals. This study demonstrates that overnourishment during early postnatal development leads to profound changes in body weight at weaning, which tended to abate with maturation. Thus the effects of long-term dietary intervention postweaning can override those of litter size-induced obesity.

scholarly journals Energy homeostasis in apolipoprotein AIV and cholecystokinin-deficient mice

2017 ◽  
Vol 313 (5) ◽  
pp. R535-R548 ◽  
Author(s):  
Jonathan Weng ◽  
Danwen Lou ◽  
Stephen C. Benoit ◽  
Natalie Coschigano ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Fat Mass ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Lipid Transport ◽  
Fat Absorption ◽  
High Fat ◽  
Reduced Body ◽  
Brown Adipose

Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK interact to prolong satiating signals. In the present study, we hypothesized that ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding. To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV-KO, and CCK-KO mice had comparable energy intake and expenditure, body weight, fat mass, fat absorption, and plasma parameters relative to the controls. In contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable body weight and fat mass, as well as lower energy expenditure at some time points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity relative to wild-type mice, despite having normal food intake. Furthermore, ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as well as enhanced energy expenditure. These observations suggest that mice lacking ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired lipid transport and elevated energy expenditure.

scholarly journals Differential Effects of Combined Soluble Epoxide Hydrolase Inhibitor t-TUCB and n-3 Epoxides in Diet-Induced Obesity

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 1260-1260
Author(s):  
Yang Yang ◽  
Xinyun Xu ◽  
Christophe Morisseau ◽  
Bruce Hammock ◽  
Ahmed Bettaieb ◽  
...  
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Protein Expression ◽  
Cold Tolerance ◽  
High Fat Diet ◽  
Epoxide Hydrolase ◽  
Soluble Epoxide Hydrolase ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Brown Adipose

Abstract Objectives Brown adipose tissue (BAT) is a promising target for obesity prevention. N-3 epoxides are fatty acid epoxides produced from n-3 polyunsaturated fatty acids and shown to be beneficial for health. However, these epoxides are unstable and quickly metabolized by the cytosolic soluble epoxide hydrolase (sEH). Here, we investigated the effects of sEH inhibitor (t-TUCB) alone or combined with two different n-3 epoxides on BAT activation in the development of diet-induced obesity and associated metabolic disorders. Methods Male C57BL6/J mice were fed a high-fat diet and received either of the following treatment: the vehicle control, t-TUCB alone (T), or t-TUCB combined with 19,20-EDP (T + EDP) or 17,18-EEQ (T + EEQ) via osmotic minipump delivery near the interscapular BAT for 6 weeks. Mice were examined for changes in body weight, food intake, glucose, insulin, and cold tolerance tests, and indirect calorimetry. Blood and tissue biochemical analyses were also performed to assess changes in metabolic homeostasis. Results Although no differences in food intake were observed, there were small but significant increases in body weight in both T and T + EDP groups. Mice in the T + EDP and T + EEQ groups showed significant decreases in fasting glucose and serum TG levels, higher core body temperature, and better cold tolerance compared to the controls. However, heat production was significantly increased only in the T + EEQ group. Thermogenic UCP1 protein expression showed a moderate, but not significant, increase in the T + EEQ group. On the other hand, PGC1 α protein expression was significantly increased in the T, T + EDP, and T + EEQ groups compared to the controls. Perilipin protein expression and phosphorylation were also significantly increased in the three treated groups. In contrast, protein expression of FABP4 and HSL was only increased in the T and T + EDP groups, and CD36 protein expression was only increased in the T + EEQ group. Conclusions Our results suggest that sEH pharmacological inhibition by t-TUCB combined with n-3 epoxides may prevent high-fat diet-induced glucose and lipid disorders, in part through increased thermogenesis and upregulating of protein expression of thermogenic and lipid metabolic genes. Funding Sources The work was supported by NIH grants to L.Z., A.B., and B.D.H.

Insulin and metabolic efficiency in rats. II. Effects of NE and cold exposure

1986 ◽  
Vol 251 (6) ◽  
pp. R1118-R1125
Author(s):  
T. J. Bartness ◽  
C. J. Billington ◽  
A. S. Levine ◽  
J. E. Morley ◽  
N. E. Rowland ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Energy Expenditure ◽  
Cold Exposure ◽  
Diabetic Rats ◽  
Metabolic Efficiency ◽  
Maximal Energy ◽  
Brown Adipose

The role of insulin in metabolic efficiency (ME, i.e., efficiency of body wt gain) was examined under conditions of maximal energy expenditure in control and diabetic rats. Long-lasting insulin was administered using a protocol that did not affect food intake and increased ME in both groups. Half the animals were injected chronically with norepinephrine (NE). NE alone in controls decreased body weight and ME and increased brown adipose tissue (BAT) growth, thermogenic potential [cytochrome c oxidase activity (COA)], and lipoprotein lipases (LPL) activity; however, in diabetics, body weight, ME, and food intake all decreased and only BAT LPL activity and DNA content increased. The combination of NE and insulin increased BAT protein and COA in diabetics; in controls, all BAT measures were further increased and ME was intermediate to that of either treatment alone. Cold exposure decreased body weight and ME, increased food intake and qualitatively produced similar increases in BAT growth, COA, and LPL activity in both controls and diabetics. In diabetics, combined cold exposure and insulin did not affect the increase in BAT growth or LPL activity resulting from either treatment alone, but in controls this combination decreased BAT growth and COA. It is concluded that, even under conditions of maximal energy expenditure, both extremes of basal insulin status result in decreased BAT growth and thermogenic potential, but have opposite effects on ME.

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