Abstract 19727: ROCK2 Mediates Browning of White Fat and Protects Against Obesity

Circulation ◽  
2014 ◽  
Vol 130 (suppl_2) ◽  
Author(s):  
Phetcharat Chen ◽  
Christina Park ◽  
Eltayeb Karrar ◽  
Chaoyung Wang ◽  
James Liao
Keyword(s):  
Weight Gain ◽  
Body Temperature ◽  
Cold Exposure ◽  
Diet Induced Obesity ◽  
Therapeutic Benefits ◽  
White Adipocytes ◽  
Important Regulator ◽  
And Function ◽  
White Fat ◽  
Adipocyte Development

Background: The Rho-activated kinases (ROCK1 and ROCK2) are serine threonine kinases that are ubiquitously expressed with higher levels of ROCK2 compared to ROCK1 in adipocytes. Recent studies suggest that ROCK2 may be an important regulator of energy metabolism and obesity. However, its role in adipocyte development and function is unknown. Methods and Result: To determine the role of ROCK2 in adipocyte development and obesity, we generated adipocyte-specific deletion (ROCK2 adipoQ-/- ) and overexpression (CA-ROCK adipoQ+/+ ) of ROCK2 in mice. Compared to control mice, CA-ROCK adipoQ+/+ mice exhibited increased browning of inguinal white adipose tissue (iWAT). Indeed, immunohistochemical staining of iWAT in CA-ROCK adipoQ+/+ mice showed that UCP1 was upregulated. Furthermore, CA-ROCK adipoQ+/+ mice on high fat diet were resistant to weight gain and obesity for up to 18 weeks. This is in contrast to ROCK2 adipoQ-/- mice, which developed more weight gain or obesity than control mice. To determine the physiological effects of ROCK2 on browning of iWAT, control and ROCK2 adipoQ-/- mice were exposed to 4°C for 1 week. In control mice, cold exposure increased ROCK2 activity and lead to browning of iWAT. However, the iWAT in ROCK2 adipoQ-/- mice failed to undergo browning. Analysis of gene expression in iWAT demonstrated increased UCP1 and mitochondria proteins in control but not ROCK2 adipoQ-/- mice. Thermal imaging revealed that ROCK2 adipoQ-/- mice were unable to maintain basal body temperature after prolonged cold exposure. In contrast, the heat map of the CA-ROCK adipoQ+/+ mice showed an elevation of body temperature, particularly in areas of iWAT as compared to that of control littermates. Conclusions: ROCK2 mediates the “browning” of white adipocytes and prevents the development of obesity through increased thermogenesis. These findings suggest that the activation of ROCK2 in adipocytes may have therapeutic benefits in preventing diet-induced obesity.

scholarly journals Helminth infection modulates number and function of adipose tissue Tregs in high fat diet-induced obesity

2021 ◽  
Author(s):  
Camila Queiroz-Glauss ◽  
Mariana Vieira ◽  
Marcela Helena Gonçalves-Pereira ◽  
Stephanie Almeida ◽  
Rachel Freire ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
High Fat Diet ◽  
Metabolic Diseases ◽  
Experimental Studies ◽  
Treg Cells ◽  
Loss Of Function ◽  
High Fat ◽  
Diet Induced Obesity ◽  
And Function

Background: Epidemiological and experimental studies have shown a protective effect of helminth infections in weight gain and against the development of metabolic dysfunctions in the host. However, the mechanisms induced by the parasite that regulate the development of metabolic diseases in the host are unclear. The present study aimed to verify the influence of Heligmosomoides polygyrus infection in early stages of high fat diet-induced obesity. Principal Findings: The presence of infection was able to prevent exacerbated weight gain in mice fed with high fat diet when compared to non-infected controls. In addition, infected animals displayed improved insulin sensitivity and decreased fat accumulation in the liver. Obesity-associated inflammation was reduced in the presence of infection, demonstrated by higher levels of IL10 and adiponectin, increased infiltration of Th2 and eosinophils in adipose tissue of infected animals. Of note, the parasite infection was associated with increased Treg frequency in adipose tissue which showed higher expression of cell surface markers of function and activation, like LAP and CD134. The infection could also revert the loss of function in Tregs associated with high fat diet. Conclusion: These data suggest that H. polygyrus infection can prevent weight gain and metabolic syndrome in animals fed with high fat diet associated with modulations of adipose tissue Treg cells.

Functional assessment of white and brown adipocyte development and energy metabolism in cell culture. Dissociation of terminal differentiation and thermogenesis in brown adipocytes

1995 ◽  
Vol 108 (10) ◽  
pp. 3171-3180
Author(s):  
S. Klaus ◽  
M. Ely ◽  
D. Encke ◽  
G. Heldmaier
Keyword(s):  
Uncoupling Protein ◽  
Terminal Differentiation ◽  
Brown Adipocyte ◽  
Index Number ◽  
Brown Adipocytes ◽  
White Adipocytes ◽  
Dwarf Hamster ◽  
Microscopy Analysis ◽  
White Fat ◽  
Adipocyte Development

We investigated the effect of insulin, triiodothyronine (T3) and dexamethasone (a synthetic glucocorticoid) on differentiation, lipid metabolism and thermogenesis of preadipocytes isolated from white fat (WAT) and brown fat (BAT) from the Siberian dwarf hamster (Phodopus sungorus). Cell cultures from WAT and BAT were chronically treated with the above hormones alone or in any combination. After differentiation (day 8 or 9 of culture) we measured the following parameters: adipogenic index (number × size of adipocytes), protein content, lipolysis, cell respiration, and expression of the uncoupling protein UCP, which is unique to mitochondria of brown adipocytes. Insulin was the most important adipogenic factor for brown and white adipocytes and necessary for terminal differentiation, whereas dexamethasone alone completely inhibited differentiation. T3 had no effect on adipogenesis in WAT cultures, but further increased insulin stimulated adipogenesis in BAT cultures. Basal lipolysis was higher in WAT than in BAT cultures except when dexamethasone was present, which stimulated lipolysis in both culture types to the same extent. T3 had a pronounced dose dependent lipolytic effect on WAT cultures but very little effect on BAT cultures. Respiration rates were generally higher in differentiated adipocytes than in fibroblast like cells. T3 had no effect on thermogenesis in WAT cultures but increased thermogenesis in BAT cultures, and this was further elevated by insulin. UCP expression in BAT cultures could be detected by western blot in insulin treated, T3 treated and insulin+T3 treated cultures with highest expression in the latter. These results imply a possible dissociation of terminal differentiation and thermogenic function of brown adipocytes. In WAT cultures there was also a low level of UCP detectable in the insulin+T3 treated cultures. Immuno-fluorescence microscopy analysis revealed the presence of UCP in 10–15% of adipocytes from WAT cultures (in BAT cultures: 90%), indicating the presence of some brown preadipocytes in typical WAT deposits.

scholarly journals Overexpression of nuclear receptor SHP in adipose tissues affects diet-induced obesity and adaptive thermogenesis

2010 ◽  
Vol 298 (5) ◽  
pp. E961-E970 ◽  
Author(s):  
Imene Tabbi-Anneni ◽  
Robert Cooksey ◽  
Viswanath Gunda ◽  
Shiguo Liu ◽  
Aubrey Mueller ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Nuclear Receptor ◽  
Fat Mass ◽  
Cold Exposure ◽  
Metabolic Rates ◽  
Adipose Tissues ◽  
Fat Mass Index ◽  
Adaptive Thermogenesis ◽  
Diet Induced Obesity

The orphan nuclear receptor small heterodimer partner (SHP) regulates metabolic pathways involved in hepatic bile acid production and both lipid and glucose homeostasis via the transcriptional repression of other nuclear receptors. In the present study, we generated fat-specific SHP-overexpressed transgenic (TG) mice and determined the potential role of SHP activation, specifically in adipocytes, in the regulation of adipose tissue function in response to stressors. We determined in 2 mo-old SHP TG mice body weight, fat mass index, adipose tissues morphology, thermogenic and metabolic gene expression, metabolic rates at baseline and in response to β adrenergic receptor agonists, and brown fat ultrastructural changes in response to cold exposure (6–48 h). Mice were fed a 10-wk high-fat diet (HFD; 42% fat). Weight gain, fat mass index, adipose tissues morphology, glucose tolerance, and metabolic rates were determined at the end of the feeding. Young TG mice had increased body weight and adiposity; however, their energy metabolism was increased and brown fat function was enhanced in response to cold exposure through the activation of thermogenic genes and mitochondrial biogenesis. SHP overexpression exacerbated the diet-induced obesity phenotype as evidence by marked weight gain over time, increased adiposity, and severe glucose intolerance compared with wild-type mice fed a HFD. In addition, SHP-TG mice fed HFD had decreased diet-induced adaptive thermogenesis, increased food intake, and decreased physical activity. In conclusion, SHP activation in adipocytes strongly affects weight gain and diet-induced obesity. Developing a synthetic compound to antagonize the effect of SHP may prove to be useful in treating obesity.

scholarly journals Disruption of beta3 adrenergic receptor increases susceptibility to DIO in mouse

2016 ◽  
Vol 231 (3) ◽  
pp. 259-269 ◽  
Author(s):  
Nailliw Z Preite ◽  
Bruna P P do Nascimento ◽  
Cynthia R Muller ◽  
Anna Laura V Américo ◽  
Talita S Higa ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Cold Exposure ◽  
High Fat Diet ◽  
Thermal Response ◽  
Adrenergic Stimulation ◽  
Diet Induced Obesity ◽  
White Adipocytes ◽  
Brown Adipose ◽  
Normal Expression ◽  
Β Adrenergic Receptors

The brown adipose tissue (BAT) mediates adaptive changes in metabolic rate by responding to the sympathetic nervous system through β-adrenergic receptors (AR). Here, we wished to define the role played by the ARβ3 isoform in this process. This study focused on the ARβ3 knockout mice (ARβ3KO), including responsiveness to cold exposure, diet-induced obesity, intolerance to glucose, dyslipidaemia and lipolysis in white adipose tissue (WAT). ARβ3KO mice defend core temperature during cold exposure (4°C for 5 h), with faster BAT thermal response to norepinephrine (NE) infusion when compared with wild-type (WT) mice. Despite normal BAT thermogenesis, ARβ3KO mice kept on a high-fat diet (HFD; 40% fat) for 8 weeks exhibited greater susceptibility to diet-induced obesity, markedly increased epididymal adipocyte area with clear signs of inflammation. The HFD-induced glucose intolerance was similar in both groups but serum hypertriglyceridemia and hypercholesterolemia were less intense in ARβ3KO animals when compared with WT controls. Isoproterenol-induced lipolysis in isolated white adipocytes as assessed by glycerol release was significantly impaired in ARβ3KO animals despite normal expression of key proteins involved in lipid metabolism. In conclusion, ARβ3 inactivation does not affect BAT thermogenesis but increases susceptibility to diet-induced obesity by dampening WAT lipolytic response to adrenergic stimulation.

scholarly journals Lactobacillus amylovorus KU4 ameliorates diet-induced obesity in mice by promoting adipose browning through PPARγ signaling

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Sung-Soo Park ◽  
Yeon-Joo Lee ◽  
Hyuno Kang ◽  
Garam Yang ◽  
Eun Jeong Hong ◽  
...  
Keyword(s):  
Probiotic Bacterium ◽  
Protective Effects ◽  
Diet Induced Obesity ◽  
White Adipocytes ◽  
Lactobacillus Amylovorus ◽  
Obesity In Mice ◽  
Lactate Levels ◽  
Transcriptional Complex ◽  
And Function

AbstractBrowning of white adipose tissue (WAT) is currently considered a potential therapeutic strategy to treat diet-induced obesity. While some probiotics have protective effects against diet-induced obesity, the role of probiotics in adipose browning has not been explored. Here, we show that administration of the probiotic bacterium Lactobacillus amylovorus KU4 (LKU4) to mice fed a high-fat diet (HFD) enhanced mitochondrial levels and function, as well as the thermogenic gene program (increased Ucp1, PPARγ, and PGC-1α expression and decreased RIP140 expression), in subcutaneous inguinal WAT and also increased body temperature. Furthermore, LKU4 administration increased the interaction between PPARγ and PGC-1α through release of RIP140 to stimulate Ucp1 expression, thereby promoting browning of white adipocytes. In addition, lactate, the levels of which are elevated in plasma of HFD-fed mice following LKU4 administration, elicited the same effect on the interaction between PPARγ and PGC-1α in 3T3-L1 adipocytes, leading to a brown-like adipocyte phenotype that included enhanced Ucp1 expression, mitochondrial levels and function, and oxygen consumption rate. Together, these data reveal that LKU4 facilitates browning of white adipocytes through the PPARγ-PGC-1α transcriptional complex, at least in part by increasing lactate levels, leading to inhibition of diet-induced obesity.

1759-P: Prostaglandin PGE2 Receptor EP4 Signaling Deficiency in Microglia Reduces Weight Gain with Transient Glucose Improvements in Diet-Induced Obesity

Diabetes ◽  
2020 ◽  
Vol 69 (Supplement 1) ◽  
pp. 1759-P
Author(s):  
ANZELA NIRAULA ◽  
RACHAEL FASNACHT ◽  
KELLY M. NESS ◽  
JEREMY FREY ◽  
MAURICIO D. DORFMAN ◽  
...  
Keyword(s):  
Weight Gain ◽  
Diet Induced Obesity ◽  
Pge2 Receptor

ADAPTATION OF WHITE MICE (MUS MUSCULUS) TO REPEATED COOLING

1967 ◽  
Vol 45 (3) ◽  
pp. 321-327 ◽  
Author(s):  
David M. Ogilvie
Keyword(s):  
Body Temperature ◽  
Rectal Temperature ◽  
Cold Exposure ◽  
Mus Musculus ◽  
Room Temperature ◽  
The Body ◽  
Progressive Decrease

The effects, on the body temperature of white mice, of repeated short exposures to cold were investigated using two methods of restraint. Animals held in a flattened posture became hypothermic at room temperature, cooled more than five times as fast at −10 °C as mice that could adopt a heat-conserving posture, and continued to cool for some time after they were removed from the cold. With repeated tests, cooling at room temperature decreased, and an improvement in re warming ability was observed. In addition, with lightly restrained mice, the fall in rectal temperature during cold exposure showed a progressive decrease, a phenomenon not observed with severely restrained animals.

Body temperature regulation and oxygen consumption in young chicks fed thyroid hormone

1991 ◽  
Vol 69 (7) ◽  
pp. 1842-1847 ◽  
Author(s):  
Gregory K. Snyder ◽  
Joseph R. Coelho ◽  
Dalan R. Jensen
Keyword(s):  
Oxygen Consumption ◽  
Thyroid Hormone ◽  
Body Temperature ◽  
Ambient Temperature ◽  
Cold Exposure ◽  
Elevated Serum ◽  
Body Temperatures ◽  
Serum Thyroid Hormone ◽  
Regulate Body Temperature ◽  
Young Chicks

In chicks the ability to regulate body temperature to adult levels develops during the first 2 weeks of life. We examined whether the ability of young chicks to regulate body temperature is increased by elevated levels of the thyroid hormone 3,3′5-triiodothyronine. By 13 days following hatch, body temperatures of chicks were not significantly different from those expected for adult birds. Furthermore, at an ambient temperature of 10 °C, 13-day-old control chicks were able to maintain body temperature, and elevated serum thyroid hormone levels did not increase rates of oxygen consumption or body temperature above control values. Six-day-old chicks had body temperatures that were significantly lower than those of the 13-day-old chicks and were not able to regulate body temperature when exposed to an ambient temperature of 10 °C. On the other hand, 6-day-old chicks with elevated serum thyroid hormone had significantly higher rates of oxygen consumption than 6-day-old control chicks, and were able to maintain constant body temperatures during cold exposure. The increased oxygen consumption rates and improved ability to regulate body temperature during cold exposure were correlated with increased citrate synthase activity in skeletal muscle. Our results support the argument that thyroid hormones play an important role in the development of thermoregulatory ability in neonate birds by stimulating enzyme activities associated with aerobic metabolism.

Phenobarbital Effects on Weight Gain and Circadian Cycling of Food Intake and Body Temperature

1980 ◽  
Vol 165 (3) ◽  
pp. 473-479 ◽  
Author(s):  
C. Peraino ◽  
C. F. Ehret ◽  
K. R. Groh ◽  
J. C. Meinert ◽  
G. D'Arcy-Gomez
Keyword(s):  
Weight Gain ◽  
Food Intake ◽  
Body Temperature

scholarly journals Antiobesity and Hypolipidemic Activity of Moringa oleifera Leaves against High Fat Diet-Induced Obesity in Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-9 ◽  
Author(s):  
Souravh Bais ◽  
Guru Sewak Singh ◽  
Ramica Sharma
Keyword(s):  
Body Weight ◽  
Body Temperature ◽  
Total Cholesterol ◽  
High Fat Diet ◽  
Moringa Oleifera ◽  
Chronic Administration ◽  
The Body ◽  
Atherogenic Index ◽  
High Fat ◽  
Diet Induced Obesity

In the present study, the methanolic extract of Moringa oleifera leaves (MEMOL) was evaluated for antiobesity activity in rats. The antiobesity potential of MEMOL was studied against high fat diet-induced obesity (HFD) in rats. In this study, chronic administration of HFD in rats produced hypercholesterolemia (116.2 ± 0.27 mg/dL), which led to an increase in the body weight (225 gr), total cholesterol, triglycerides (263.0 ± 4.69 mg/dL), and attenuation in the levels of HDL (34.51 ± 2.20 mg/dL) as well as changes in body temperature of animals. Treatment of obese rats with MEMOL for 49 days resulted in a significant (P<0.001) change in body weight, total cholesterol, triglycerides, and LDL level along with a significant (P<0.001) increase in body temperature as compared to the HFD-induced obesity. MEMOL treated rats also showed a significant decrease in the level of liver biomarkers, organ weight, and blood glucose level. Further, rats treated with MEMOL (200 mg and 400 mg/kg) show reduced atherogenic index (1.7 ± 0.6 and 0.87 ± 0.76). The results indicate that the rats treated with Moringa oleifera (MO) have significantly attenuated the body weight without any change in the feed intake and also elicited significant thermogenic effect and to act as hypolipidemic and thermogenic property in obesity related disorders.

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