scholarly journals Thermoregulatory role of ghrelin in the induction of torpor under a restricted feeding condition

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Takahiro Sato ◽  
Kanae Oishi ◽  
Daisuke Koga ◽  
Takanori Ida ◽  
Yusuke Sakai ◽  
...  
Keyword(s):  
Arcuate Nucleus ◽  
Uncoupling Protein ◽  
Restricted Feeding ◽  
Uncoupling Protein 1 ◽  
Feeding Condition ◽  
Nervous System Activity ◽  
Brown Adipose ◽  
Hypothalamic Arcuate Nucleus ◽  
Sympathetic Nervous

AbstractGhrelin, a circulating orexigenic hormone secreted from the stomach, stimulates appetite and food intake by activating the hypothalamic arcuate nucleus. Administration of exogenous ghrelin exerts anabolic effects, causing weight gain, increased adiposity, and decreased metabolism. Body temperature (BT), which is determined by the balance of heat production and heat loss, must be strictly regulated to maintain proper cellular function and metabolism. However, the role of ghrelin in thermoregulation remains unclear. In this study, we found that ghrelin was essential for decreasing BT when mice are placed under calorie restriction. Elevated ghrelin concentrations induced by fasting correlated with significant decreases in BT, a hibernation-like state called torpor. Ghrelin-deficient (Ghrl−/−) animals could not enter torpor. The BT of Ghrl−/− mice also remained high under restricted feeding, but the animals gradually entered precipitous hypothermia, indicating thermoregulatory impairment. These effects of ghrelin on thermoregulation were the result of suppression of sympathetic nervous system activity input to brown adipose tissue; in the absence of ghrelin, it was not possible to suppress uncoupling protein 1 (ucp1) expression and decrease BT in low-energy states. Together, these findings demonstrate that ghrelin is an essential circulating hormone involved in lowering BT.

scholarly journals The role of the uncoupling protein 1 (UCP1) on the development of obesity and type 2 diabetes mellitus

2012 ◽  
Vol 56 (4) ◽  
pp. 215-225 ◽  
Author(s):  
Letícia de Almeida Brondani ◽  
Taís Silveira Assmann ◽  
Guilherme Coutinho Kullmann Duarte ◽  
Jorge Luiz Gross ◽  
Luís Henrique Canani ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Metabolic Diseases ◽  
Uncoupling Protein ◽  
Uncoupling Protein 1 ◽  
Exon 2 ◽  
Brown Adipose

It is well established that genetic factors play an important role in the development of both type 2 diabetes mellitus (DM2) and obesity, and that genetically susceptible subjects can develop these metabolic diseases after being exposed to environmental risk factors. Therefore, great efforts have been made to identify genes associated with DM2 and/or obesity. Uncoupling protein 1 (UCP1) is mainly expressed in brown adipose tissue, and acts in thermogenesis, regulation of energy expenditure, and protection against oxidative stress. All these mechanisms are associated with the pathogenesis of DM2 and obesity. Hence, UCP1 is a candidate gene for the development of these disorders. Indeed, several studies have reported that polymorphisms -3826A/G, -1766A/G and -112A/C in the promoter region, Ala64Thr in exon 2 and Met299Leu in exon 5 of UCP1 gene are possibly associated with obesity and/or DM2. However, results are still controversial in different populations. Thus, the aim of this study was to review the role of UCP1 in the development of these metabolic diseases.

Regulation of beta 3-adrenergic receptor mRNA by sympathetic nerves and glucocorticoids in BAT of Zucker obese rats

1995 ◽  
Vol 269 (3) ◽  
pp. R519-R526 ◽  
Author(s):  
T. Onai ◽  
G. Kilroy ◽  
D. A. York ◽  
G. A. Bray
Keyword(s):  
Adrenergic Receptor ◽  
Uncoupling Protein ◽  
Sympathetic Nerves ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Brown Adipose ◽  
Obese Rats ◽  
Sympathetic Nervous ◽  
Opposite Response

Impaired brown adipose tissue (BAT) thermogenesis in the genetically obese Zucker fatty (fa/fa) rat is restored to normal by adrenalectomy. We investigated the role of the sympathetic nervous system in modulating the effects of adrenalectomy by studying beta3-adrenergic receptor (AR) and uncoupling protein (UCP) mRNA levels in unilaterally sympathectomized interscapular BAT of lean and obese rats. UCP mRNA levels were increased by adrenalectomy. Sympathetic denervation prevented this adrenalectomy-induced increase in lean rats but not in obese rats. beta 3-AR mRNA was decreased in BAT of obese rats. Adrenalectomy decreased and denervation increased beta 3-AR mRNA in lean rats but the opposite response was observed to both of these manipulations in obese rats. beta 3-AR mRNA and UCP mRNA were negatively correlated in lean rats but positively correlated in obese rats. Norepinephrine increased UCP mRNA levels in denervated BAT of both lean and obese rats and decreased beta 3-AR mRNA in lean rats but not obese rats. These data suggest that the regulation of the beta 3-AR gene in response to sympathetic stimuli and glucocorticoids is abnormal in the obese rat.

Activation of pattern recognition receptors in brown adipocytes induces inflammation and suppresses uncoupling protein 1 expression and mitochondrial respiration

2014 ◽  
Vol 306 (10) ◽  
pp. C918-C930 ◽  
Author(s):  
Jiyoung Bae ◽  
Carolyn J. Ricciardi ◽  
Debora Esposito ◽  
Slavko Komarnytsky ◽  
Pan Hu ◽  
...  
Keyword(s):  
Pattern Recognition ◽  
Mitochondrial Respiration ◽  
Uncoupling Protein ◽  
Mapk Signaling ◽  
Pattern Recognition Receptors ◽  
Brown Adipocyte ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Brown Adipose

Pattern recognition receptors (PRR), Toll-like receptors (TLR), and nucleotide-oligomerization domain-containing proteins (NOD) play critical roles in mediating inflammation and modulating functions in white adipocytes in obesity. However, the role of PRR activation in brown adipocytes, which are recently found to be present in adult humans, has not been studied. Here we report that mRNA of TLR4, TLR2, NOD1, and NOD2 is upregulated, paralleled with upregulated mRNA of inflammatory cytokines and chemokines in the brown adipose tissue (BAT) of the obese mice. During brown adipocyte differentiation, mRNA and protein expression of NOD1 and TLR4, but not TLR2 and NOD2, is also increased. Activation of TLR4, TLR2, or NOD1 in brown adipocytes induces activation of NF-κB and MAPK signaling pathways, leading to inflammatory cytokine/chemokine mRNA expression and/or protein secretion. Moreover, activation of TLR4, TLR2, or NOD1 attenuates both basal and isoproterenol-induced uncoupling protein 1 (UCP-1) expression without affecting mitochondrial biogenesis and lipid accumulation in brown adipocytes. Cellular bioenergetics measurements confirm that attenuation of UCP-1 expression by PRR activation is accompanied by suppression of both basal and isoproterenol-stimulated oxygen consumption rates and isoproterenol-induced uncoupled respiration from proton leak; however, maximal respiration and ATP-coupled respiration are not changed. Further, the attenuation of UCP-1 by PRR activation appears to be mediated through downregulation of the UCP-1 promoter activities. Taken together, our results demonstrate the role of selected PRR activation in inducing inflammation and downregulation of UCP-1 expression and mitochondrial respiration in brown adipocytes. Our results uncover novel targets in BAT for obesity treatment and prevention.

Attenuated cold-induced increase in mRNA for uncoupling protein in brown adipose tissue of obese (ob/ob) mice

1988 ◽  
Vol 66 (3) ◽  
pp. 193-198 ◽  
Author(s):  
Susanna Reichling ◽  
Hasmukh V. Patel ◽  
Karl B. Freeman ◽  
Anna-Lisa Kates ◽  
Jean Himms-Hagen
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Uncoupling Protein ◽  
Obese Mice ◽  
Absolute Increase ◽  
Nervous System Activity ◽  
Brown Adipose ◽  
Sympathetic Nervous ◽  
Uncoupling Protein Mrna ◽  
Thermogenic Response

The level of mRNA for uncoupling protein was measured in brown adipose tissue of young (8–10 weeks) and old (11 months) lean and ob/ob mice using a cDNA clone constructed previously. The level of poly(A)+ RNA was also measured using an oligo(dT)18 probe. Mice were kept at 28 °C or exposed to 14 °C for 12 h. The level of mRNA for uncoupling protein was normal in brown adipose tissue of younger obese mice but reduced in brown adipose tissue of old obese mice. The cold-induced absolute increase in uncoupling protein mRNA was smaller in obese mice, regardless of age. It is concluded that the known attenuation of the acute thermogenic response of brown adipose tissue of the ob/ob mouse to cold is accompanied by a similar attenuation of the initiation of the trophic response. It is likely, however, that these defects are secondary to the chronic reduction in sympathetic nervous system activity in brown adipose tissue of the ob/ob mouse, which results in a functional atrophy of the tissue.

scholarly journals The Role of Uncoupling Protein 1 in the Metabolism and Adiposity of RIIβ-Protein Kinase A-Deficient Mice

2004 ◽  
Vol 18 (9) ◽  
pp. 2302-2311 ◽  
Author(s):  
Michael A. Nolan ◽  
Maria A. Sikorski ◽  
G. Stanley McKnight
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Protein Kinase ◽  
Protein Kinase A ◽  
Uncoupling Protein ◽  
Mrna Level ◽  
Regulatory Subunit ◽  
Uncoupling Protein 1 ◽  
Brown Adipose ◽  
Kinase A

Abstract Mice lacking the RIIβ regulatory subunit of protein kinase A exhibit a 50% reduction in white adipose tissue stores compared with wild-type littermates and are resistant to diet-induced obesity. RIIβ−/− mice also have an increase in resting oxygen consumption along with a 4-fold increase in the brown adipose-specific mitochondrial uncoupling protein 1 (UCP1). In this study, we examined the basis for UCP1 induction and tested the hypothesis that the induced levels of UCP1 in RIIβ null mice are essential for the lean phenotype. The induction of UCP1 occurred at the protein but not the mRNA level and correlated with an increase in mitochondria in brown adipose tissue. Mice lacking both RIIβ and UCP1 (RIIβ−/−/Ucp1−/−) were created, and the key parameters of metabolism and body composition were studied. We discovered that RIIβ−/− mice exhibit nocturnal hyperactivity in addition to the increased oxygen consumption at rest. Disruption of UCP1 in RIIβ−/− mice reduced basal oxygen consumption but did not prevent the nocturnal hyperactivity. The double knockout animals also retained the lean phenotype of the RIIβ null mice, demonstrating that induction of UCP1 and increased resting oxygen consumption is not the cause of leanness in the RIIβ mutant mice.

scholarly journals Immunoreactivity of Canine Liposarcoma to Muscle and Brown Adipose Antigens

2017 ◽  
Vol 54 (6) ◽  
pp. 885-891 ◽  
Author(s):  
Elise E. B. LaDouceur ◽  
Sarah E. Stevens ◽  
Jason Wood ◽  
Christopher M. Reilly
Keyword(s):  
Uncoupling Protein ◽  
Smooth Muscle Actin ◽  
Antigen Expression ◽  
Muscle Actin ◽  
Uncoupling Protein 1 ◽  
Diagnostic Challenge ◽  
Brown Adipose ◽  
Well Differentiated ◽  
Relationship Of ◽  
Oil Red O

Liposarcoma, rhabdomyosarcoma, and hibernoma share some overlapping histologic and immunohistochemical features. Although immunohistochemistry (IHC) is commonly used in the diagnosis of these neoplasms, expression of muscle markers has been reported in human liposarcoma and canine hibernoma in addition to rhabdomyosarcoma. Thus, these neoplasms are a diagnostic challenge but important to distinguish because of differences in prognosis and treatment. Rhabdomyosarcoma and liposarcoma are both malignant, but rhabdomyosarcoma has a higher potential for metastasis. In contrast, hibernomas are benign with low risk of recurrence. This study investigated expression of the muscle markers desmin, myogenin, and α-smooth muscle actin (α-SMA) and the brown fat marker uncoupling protein 1 (UCP1) in 25 cases of canine liposarcoma using IHC. Oil red O histochemistry was performed to confirm the presence of lipid and the diagnosis of liposarcoma in cases that were not well-differentiated. The 25 cases included 15 well-differentiated, 5 pleomorphic, 3 myxoid, and 2 dedifferentiated subtypes of liposarcoma. By IHC, 23 of 25 expressed UCP1, 7 of 25 expressed α-SMA, 7 of 25 expressed desmin, and 3 of 25 expressed myogenin with no clear relationship of antigen expression and tumor subtype. These findings clarify the immunohistochemical profile of canine liposarcoma and suggest overlap in the expression of several muscle antigens and UCP1 between liposarcoma, hibernoma, and rhabdomyosarcoma.

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