The Experts below are selected from a list of 17997 Experts worldwide ranked by ideXlab platform
Masayuki Saito - One of the best experts on this subject based on the ideXlab platform.
-
Thermogenic ability of Uncoupling Protein 1 in beige adipocytes in mice.
PloS one, 2013Co-Authors: Yuko Okamatsu-ogura, Keigo Fukano, Ayumi Tsubota, Akihiro Uozumi, Akira Terao, Kazuhiro Kimura, Masayuki SaitoAbstract:Chronic adrenergic activation leads to the emergence of beige adipocytes in some depots of white adipose tissue in mice. Despite their morphological similarities to brown adipocytes and their expression of Uncoupling Protein 1 (UCP1), a thermogenic Protein exclusively expressed in brown adipocytes, the beige adipocytes have a gene expression pattern distinct from that of brown adipocytes. However, it is unclear whether the thermogenic function of beige adipocytes is different from that of classical brown adipocytes existing in brown adipose tissue. To examine the thermogenic ability of UCP1 expressed in beige and brown adipocytes, the adipocytes were isolated from the fat depots of C57BL/6J mice housed at 24°C (control group) or 10°C (cold-acclimated group) for 3 weeks. Morphological and gene expression analyses revealed that the adipocytes isolated from brown adipose tissue of both the control and cold-acclimated groups consisted mainly of brown adipocytes. These brown adipocytes contained large amounts of UCP1 and increased their oxygen consumption when stimulated with norepinephirine. Adipocytes isolated from the perigonadal white adipose tissues of both groups and the inguinal white adipose tissue of the control group were white adipocytes that showed no increase in oxygen consumption after norepinephrine stimulation. Adipocytes isolated from the inguinal white adipose tissue of the cold-acclimated group were a mixture of white and beige adipocytes, which expressed UCP1 and increased their oxygen consumption in response to norepinephrine. The UCP1 content and thermogenic ability of beige adipocytes estimated on the basis of their abundance in the cell mixture were similar to those of brown adipocytes. These results revealed that the inducible beige adipocytes have potent thermogenic ability comparable to classical brown adipocytes.
-
indispensable role of mitochondrial ucp1 for antiobesity effect of β3 adrenergic stimulation
American Journal of Physiology-endocrinology and Metabolism, 2006Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Hitoshi Yamashita, Yuko Okamatsuogura, Asako Omachi, Yukiko Matsushita, Masayuki SaitoAbstract:Mitochondrial Uncoupling Protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy ...
-
Uncoupling Protein 1 is necessary for norepinephrine induced glucose utilization in brown adipose tissue
Diabetes, 2005Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Yuko Oguraokamatsu, Chitoku Toda, Hitoshi Yamashita, Masayuki SaitoAbstract:Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the β-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial Uncoupling Protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated Protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.
-
Uncoupling Protein 1 is necessary for norepinephrine induced glucose utilization in brown adipose tissue
Diabetes, 2005Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Yuko Oguraokamatsu, Chitoku Toda, Hitoshi Yamashita, Masayuki SaitoAbstract:Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the β-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial Uncoupling Protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated Protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.
Hitoshi Yamashita - One of the best experts on this subject based on the ideXlab platform.
-
evodiamine improves diet induced obesity in a Uncoupling Protein 1 independent manner involvement of antiadipogenic mechanism and extracellularly regulated kinase mitogen activated Protein kinase signaling
Endocrinology, 2008Co-Authors: Ting Wang, Youxue Wang, Yasuhide Kontani, Yoshinori Kobayashi, Yuzo Sato, Nozomu Mori, Hitoshi YamashitaAbstract:Evodiamine is an alkaloidal compound with antiobesity effects that have been thought to be due to Uncoupling Protein-1 (UCP1) thermogenesis similar to the effects of capsaicin, but the underlying mechanisms are poorly understood. To clarify the mechanisms, we first examined whether the antiobesity effect of evodiamine could be attributed to the involvement of UCP1. When UCP1-knockout mice were fed a high-fat diet with 0.03% evodiamine (wt/wt) for 2 months, the increases in body weight, adiposity, and the serum levels of leptin and insulin were reduced in a manner indistinguishable from control mice fed a high-fat diet with evodiamine, suggesting that evodiamine triggered a UCP1-independent mechanism to prevent diet-induced obesity. By using preadipocyte cultures, we found that evodiamine, but not capsaicin, increased phosphorylation of ERK/MAPK, reduced the expression of transcription factors such as peroxisome proliferator-activated receptor-gamma, and strongly inhibited adipocyte differentiation. Evodiamine treatment also reduced insulin-stimulated phosphorylation of Akt, a crucial regulator of adipocyte differentiation; and the reduction of phosphorylated-Akt and augmentation of phosphorylated ERK were reversed by blockade of the MAPK kinase/MAPK signaling pathway, restoring adipogenesis in the cultures. The changes in ERK and Akt phosphorylation levels were also observed in white adipose tissues of UCP1-knockout mice fed the evodiamine diet. These findings suggest that evodiamine has a potential to prevent the development of diet-induced obesity in part by inhibiting adipocyte differentiation through ERK activation and its negative cross talk with the insulin signaling pathway.
-
indispensable role of mitochondrial ucp1 for antiobesity effect of β3 adrenergic stimulation
American Journal of Physiology-endocrinology and Metabolism, 2006Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Hitoshi Yamashita, Yuko Okamatsuogura, Asako Omachi, Yukiko Matsushita, Masayuki SaitoAbstract:Mitochondrial Uncoupling Protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy ...
-
Uncoupling Protein 1 is necessary for norepinephrine induced glucose utilization in brown adipose tissue
Diabetes, 2005Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Yuko Oguraokamatsu, Chitoku Toda, Hitoshi Yamashita, Masayuki SaitoAbstract:Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the β-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial Uncoupling Protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated Protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.
-
Uncoupling Protein 1 is necessary for norepinephrine induced glucose utilization in brown adipose tissue
Diabetes, 2005Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Yuko Oguraokamatsu, Chitoku Toda, Hitoshi Yamashita, Masayuki SaitoAbstract:Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the β-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial Uncoupling Protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated Protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.
Sheila Collins - One of the best experts on this subject based on the ideXlab platform.
-
orphan nuclear receptor nor 1 enhances 3 5 cyclic adenosine 5 monophosphate dependent Uncoupling Protein 1 gene transcription
Molecular Endocrinology, 2008Co-Authors: Naresh Kumar, Dianxin Liu, Haibo Wang, Jacques Robidoux, Sheila CollinsAbstract:Prolonged cold exposure induces nonshivering thermogenesis primarily through β-adrenergic- and cAMP-mediated regulation of Uncoupling Protein-1 (UCP1) in brown adipose tissue. Molecular mechanisms involved in this induction of Ucp1 gene transcription consists of an intricate interplay between many nuclear receptors in coordination with coactivators/corepressors. Recently, it has been shown that members of the nuclear receptor-4A (NR4A) family of orphan nuclear receptors (Nur77, Nurr1, and NOR-1) are highly responsive to cAMP-second messenger pathways. Here we have identified a new regulatory motif in the Ucp1 promoter that binds NR4As to stimulate Ucp1 gene transcription. Upon cold exposure of mice, or β-agonist treatment of mouse and human adipocytes, the expression of NR4A nuclear receptors is rapidly induced, with NOR-1 being the most robust, and this precedes increases in Ucp1 expression. A dominant-negative mutant Nur-77 receptor that prevents the transcriptional activity of NR4A receptors blocked β-...
-
p38 mitogen activated Protein kinase is the central regulator of cyclic amp dependent transcription of the brown fat Uncoupling Protein 1 gene
Molecular and Cellular Biology, 2004Co-Authors: Kiefer W Daniel, Jacques Robidoux, Alexander V Medvedev, Pere Puigserver, Lisa M Floering, Bruce M Spiegelman, Sheila CollinsAbstract:It is well established that catecholamine-stimulated thermogenesis in brown fat requires β-adrenergic elevations in cyclic AMP (cAMP) to increase expression of the Uncoupling Protein 1 (UCP1) gene. However, little is known about the downstream components of the signaling cascade or the relevant transcription factor targets thereof. Here we demonstrate that cAMP- and Protein kinase A-dependent activation of p38 mitogen-activated Protein kinase (MAPK) in brown adipocytes is an indispensable step in the transcription of the UCP1 gene in mice. By phosphorylating activating transcription factor 2 (ATF-2) and peroxisome proliferator-activated receptor gamma (PPARγ) coativator 1α (PGC-1α), members of two distinct nuclear factor families, p38 MAPK controls the expression of the UCP1 gene through their respective interactions with a cAMP response element and a PPAR response element that both reside within a critical enhancer motif of the UCP1 gene. Activation of ATF-2 by p38 MAPK additionally serves as the cAMP sensor that increases expression of the PGC-1α gene itself in brown adipose tissue. In conclusion, our findings illustrate that by orchestrating the activity of multiple transcription factors, p38 MAPK is a central mediator of the cAMP signaling mechanism of brown fat that promotes thermogenesis.
-
β adrenergic activation of p38 map kinase in adipocytes camp induction of the Uncoupling Protein 1 ucp1 gene requires p38 map kinase
Journal of Biological Chemistry, 2001Co-Authors: Wenhong Cao, Kiefer W Daniel, Alexander V Medvedev, Sheila CollinsAbstract:Because of increasing evidence that G Protein-coupled receptors activate multiple signaling pathways, it becomes important to determine the coordination of these pathways and their physiological significance. Here we show that the beta(3)-adrenergic receptor (beta(3)AR) stimulates p38 mitogen-activated Protein kinase (p38 MAPK) via PKA in adipocytes and that cAMP-dependent transcription of the mitochondrial Uncoupling Protein 1 (UCP1) promoter by beta(3)AR requires p38 MAPK. The selective beta(3)AR agonist CL316,243 (CL) stimulates phosphorylation of MAP kinase kinase 3/6 and p38 MAPK in a time- and dose-dependent manner in both white and brown adipocytes. Isoproterenol and forskolin mimicked the effect of CL on p38 MAPK. In all cases activation was blocked by the specific p38 MAPK inhibitor SB202190 (SB; 1-10 microm). The involvement of PKA in beta(3)AR-dependent p38 MAPK activation was confirmed by the ability of the PKA inhibitors H89 (20 microm) and (R(p))-cAMP-S (1 mm) to block phosphorylation of p38 MAPK. Treatment of primary brown adipocytes with CL or forskolin induced the expression of UCP1 mRNA levels (6.8- +/- 0.8-fold), and this response was eliminated by PKA inhibitors and SB202190. A similar stimulation of a 3.7-kilobase UCP1 promoter by CL and forskolin was also completely inhibited by PKA inhibitors and SB202190, indicating that these effects on UCP1 expression are transcriptional. Moreover, the PKA-dependent transactivation of the UCP1 promoter, as well as its sensitivity to SB202190, was fully reproduced by a 220-nucleotide enhancer element from the UCP1 gene. We similarly observed that increased phosphorylation of ATF-2 by CL was sensitive to both H89 and SB202190, while phosphorylation of cAMP-response element-binding Protein was inhibited only by H89. Together, these studies illustrate that p38 MAPK is an important downstream target of the beta-adrenergic/cAMP/PKA signaling pathway in adipocytes, and one of the functional consequences of this cascade is stimulation of UCP1 gene expression in brown adipocytes.
Kazuhiro Kimura - One of the best experts on this subject based on the ideXlab platform.
-
melinjo gnetum gnemon l seed extract induces Uncoupling Protein 1 expression in brown fat and protects mice against diet induced obesity inflammation and insulin resistance
Nutrition Research, 2018Co-Authors: Takeshi Yoneshiro, Akira Terao, Kazuhiro Kimura, Yuko Okamatsuogura, Ryuji Kaede, Kazuki Nagaya, Manami Saito, Julia Aoyama, Mohamed ElfekyAbstract:Dietary supplementation with melinjo (Gnetum gnemon L.) seed extract (MSE) has been proposed as an anti-obesity strategy. However, it remains unclear how MSE modulates energy balance. We tested the hypothesis that dietary MSE reduces energy intake and/or increases physical activity and metabolic thermogenesis in brown and white adipose tissue (BAT and WAT) in mice. Twenty-four C57BL/6 J mice were provided with normal diet, high-fat diet (HFD), or HFD with 1% MSE added, for 17 weeks. Food intake, spontaneous locomotor activity, hepatic triglyceride (TG) content, and blood parameters were examined. Mitochondrial thermogenesis-associated molecule and inflammatory marker expression levels in BAT and WAT were examined by quantitative PCR and western blotting. Dietary MSE did not affect energy intake or spontaneous locomotor activity, but significantly suppressed HFD-induced fat accumulation, hyperglycemia, and hyperinsulinemia. Homeostasis model assessment of insulin resistance score and hepatic TG content were both lower in the MSE-supplemented HFD-fed group than in the HFD-fed group, indicating reduced insulin resistance and a less fatty liver. Dietary MSE upregulated thermogenic Uncoupling Protein 1 (UCP1) and mitochondrial marker cytochrome c oxidase subunit IV Protein expression in BAT; this was closely associated with sirtuin 1 mRNA induction. mRNAs of adipose inflammatory markers, such as monocyte chemotactic 1 and interleukin-1, were induced by HFD but suppressed by MSE. Considering that UCP1 Protein expression is the most physiologically relevant parameter to assess the thermogenic capacities of BAT, our results indicate that dietary MSE supplementation induces BAT thermogenesis and reduces obesity-associated adipose tissue inflammation, hepatic steatosis, and insulin resistance.
-
Thermogenic ability of Uncoupling Protein 1 in beige adipocytes in mice.
PloS one, 2013Co-Authors: Yuko Okamatsu-ogura, Keigo Fukano, Ayumi Tsubota, Akihiro Uozumi, Akira Terao, Kazuhiro Kimura, Masayuki SaitoAbstract:Chronic adrenergic activation leads to the emergence of beige adipocytes in some depots of white adipose tissue in mice. Despite their morphological similarities to brown adipocytes and their expression of Uncoupling Protein 1 (UCP1), a thermogenic Protein exclusively expressed in brown adipocytes, the beige adipocytes have a gene expression pattern distinct from that of brown adipocytes. However, it is unclear whether the thermogenic function of beige adipocytes is different from that of classical brown adipocytes existing in brown adipose tissue. To examine the thermogenic ability of UCP1 expressed in beige and brown adipocytes, the adipocytes were isolated from the fat depots of C57BL/6J mice housed at 24°C (control group) or 10°C (cold-acclimated group) for 3 weeks. Morphological and gene expression analyses revealed that the adipocytes isolated from brown adipose tissue of both the control and cold-acclimated groups consisted mainly of brown adipocytes. These brown adipocytes contained large amounts of UCP1 and increased their oxygen consumption when stimulated with norepinephirine. Adipocytes isolated from the perigonadal white adipose tissues of both groups and the inguinal white adipose tissue of the control group were white adipocytes that showed no increase in oxygen consumption after norepinephrine stimulation. Adipocytes isolated from the inguinal white adipose tissue of the cold-acclimated group were a mixture of white and beige adipocytes, which expressed UCP1 and increased their oxygen consumption in response to norepinephrine. The UCP1 content and thermogenic ability of beige adipocytes estimated on the basis of their abundance in the cell mixture were similar to those of brown adipocytes. These results revealed that the inducible beige adipocytes have potent thermogenic ability comparable to classical brown adipocytes.
-
indispensable role of mitochondrial ucp1 for antiobesity effect of β3 adrenergic stimulation
American Journal of Physiology-endocrinology and Metabolism, 2006Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Hitoshi Yamashita, Yuko Okamatsuogura, Asako Omachi, Yukiko Matsushita, Masayuki SaitoAbstract:Mitochondrial Uncoupling Protein-1 (UCP1) has been thought to be a key molecule for thermogenesis during cold exposure and spontaneous hyperphagia and thereby in the autonomic regulation of energy ...
-
Uncoupling Protein 1 is necessary for norepinephrine induced glucose utilization in brown adipose tissue
Diabetes, 2005Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Yuko Oguraokamatsu, Chitoku Toda, Hitoshi Yamashita, Masayuki SaitoAbstract:Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the β-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial Uncoupling Protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated Protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.
-
Uncoupling Protein 1 is necessary for norepinephrine induced glucose utilization in brown adipose tissue
Diabetes, 2005Co-Authors: Kenichi Inokuma, Kazuhiro Kimura, Yuko Oguraokamatsu, Chitoku Toda, Hitoshi Yamashita, Masayuki SaitoAbstract:Sympathetic stimulation activates glucose utilization in parallel with fatty acid oxidation and thermogenesis in brown adipose tissue (BAT) through the β-adrenergic receptors. To clarify the roles of the principal thermogenic molecule mitochondrial Uncoupling Protein 1 (UCP1) in the sympathetically stimulated glucose utilization, we investigated the uptake of 2-deoxyglucose (2-DG) into BAT and some other tissues of UCP1-knockout (KO) mice in vivo. In wild-type (WT) mice, administration of norepinephrine (NE) accelerated the disappearance of plasma 2-DG and increased 2-DG uptake into BAT and heart without any rise of plasma insulin level. In UCP1-KO mice, the stimulatory effect of NE on 2-DG uptake into BAT, but not into heart, disappeared completely. Insulin administration increased 2-DG uptake into BAT and also heart similarly in WT and UCP1-KO mice. NE also increased the activity of AMP-activated Protein kinase (AMP kinase) in BAT of WT but not UCP1-KO mice. Our results, together with reports that the activation of AMP kinase increases glucose transport in myocytes, suggest that the sympathetically stimulated glucose utilization in BAT is due to the serial activation of UCP1 and AMP kinase.
Tobias Fromme - One of the best experts on this subject based on the ideXlab platform.
-
degradation of brown adipocyte purine nucleotides regulates Uncoupling Protein 1 activity
Molecular metabolism, 2017Co-Authors: Tobias Fromme, Karin Kleigrewe, Andreas Dunkel, Angelika Retzler, Stefanie Maurer, Natascha Fischer, Rolf Diezko, Timo Kanzleiter, Yongguo Li, Verena HirschbergAbstract:Abstract Objective Non-shivering thermogenesis in mammalian brown adipose tissue depends on thermogenic Uncoupling Protein 1. Its activity is triggered by free fatty acids while purine nucleotides mediate inhibition. During activation, it is thought that free fatty acids overcome purine-mediated inhibition. We measured the cellular concentration and the release of purine nucleotide metabolites to uncover a possible role of purine nucleotide degradation in Uncoupling Protein 1 activation. Methods With mass spectrometry, purine nucleotide metabolites were quantified in cellular homogenates and supernatants of cultured primary brown adipocytes. We also determined oxygen consumption in response to a β-adrenergic agonist. Results Upon adrenergic activation, brown adipocytes decreased the intracellular concentration of inhibitory nucleotides (ATP, ADP, GTP and GDP) and released the respective degradation products. At the same time, an increase in cellular calcium occurred. None of these phenomena occurred in white adipocytes or myotubes. The brown adipocyte expression of enzymes implicated in purine metabolic remodeling is altered upon cold exposure. Pharmacological and genetic interference of purine metabolism altered Uncoupling Protein 1 mediated uncoupled respiration. Conclusion Adrenergic stimulation of brown adipocytes lowers the intracellular concentration of purine nucleotides, thereby contributing to Uncoupling Protein 1 activation.
-
the brown and brite adipocyte marker cox7a1 is not required for non shivering thermogenesis in mice
Scientific Reports, 2015Co-Authors: Stefanie Maurer, Tobias Fromme, Lawrence I Grossman, Maik Huttemann, Martin KlingensporAbstract:The cytochrome c oxidase subunit isoform Cox7a1 is highly abundant in skeletal muscle and heart and influences enzyme activity in these tissues characterised by high oxidative capacity. We identified Cox7a1, well-known as brown adipocyte marker gene, as a cold-responsive Protein of brown adipose tissue. We hypothesised a mechanistic relationship between cytochrome c oxidase activity and Cox7a1 Protein levels affecting the oxidative capacity of brown adipose tissue and thus non-shivering thermogenesis. We subjected wildtype and Cox7a1 knockout mice to different temperature regimens and tested characteristics of brown adipose tissue activation. Cytochrome c oxidase activity, Uncoupling Protein 1 expression and maximal norepinephrine-induced heat production were gradually increased during cold-acclimation, but unaffected by Cox7a1 knockout. Moreover, the abundance of Uncoupling Protein 1 competent brite cells in white adipose tissue was not influenced by presence or absence of Cox7a1. Skin temperature in the interscapular region of neonates was lower in Uncoupling Protein 1 knockout pups employed as a positive control, but not in Cox7a1 knockout pups. Body mass gain and glucose tolerance did not differ between wildtype and Cox7a1 knockout mice fed with high fat or control diet. We conclude that brown adipose tissue function in mice does not require the presence of Cox7a1.
-
Uncoupling Protein 1 expression and high fat diets
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2011Co-Authors: Tobias Fromme, Martin KlingensporAbstract:Uncoupling Protein 1 (Ucp1) is the key component of β-adrenergically controlled nonshivering thermogenesis in brown adipocytes. This process combusts stored and nutrient energy as heat. Cold exposure not only activates Ucp1-mediated thermogenesis to maintain normothermia but also results in adaptive thermogenesis, i.e., the recruitment of thermogenic capacity in brown adipose tissue. As a hallmark of adaptive thermogenesis, Ucp1 synthesis is increased proportionally to temperature and duration of exposure. Beyond this classical thermoregulatory function, it has been suggested that Ucp1-mediated thermogenesis can also be employed for metabolic thermogenesis to prevent the development of obesity. Accordingly, in times of excess caloric intake, one may expect a positive regulation of Ucp1. The general impression from an overview of the present literature is, indeed, an increased brown adipose tissue Ucp1 mRNA and Protein content after feeding a high-fat diet (HFD) to mice and rats. The reported increases are very variable in magnitude, and the effect size seems to be independent of dietary fat content and duration of the feeding trial. In white adipose tissue depots Ucp1 mRNA is generally downregulated by HFD, indicating a decline in the number of interspersed brown adipocytes.
-
adaptive thermogenesis and thermal conductance in wild type and ucp1 ko mice
American Journal of Physiology-regulatory Integrative and Comparative Physiology, 2010Co-Authors: Carola W. Meyer, Tobias Fromme, Gerhard Heldmaier, Rebecca Oelkrug, Martin Jastroch, Monja Willershauser, Bryan C Rourke, Martin KlingensporAbstract:We compared maximal cold-induced heat production (HPmax) and cold limits between warm (WA; 27°C), moderate cold (MCA; 18°C), or cold acclimated (CA; 5°C) wild-type and Uncoupling-Protein 1 knockout...
-
Marsupial Uncoupling Protein 1 sheds light on the evolution of mammalian nonshivering thermogenesis
Physiological Genomics, 2008Co-Authors: Kerry Withers, Verena Hirschberg, Tobias Fromme, Peter B. Frappell, Gerhard Heldmaier, Stefan Taudien, Michael Helwig, Bronwyn M. Mcallan, Bruce T. FirthAbstract:Brown adipose tissue expressing Uncoupling Protein 1 (UCP1) is responsible for adaptive nonshivering thermogenesis giving eutherian mammals crucial advantage to survive the cold. The emergence of this thermogenic organ during mammalian evolution remained unknown as the identification of UCP1 in marsupials failed so far. Here, we unequivocally identify the marsupial UCP1 ortholog in a genomic library of Monodelphis domestica. In South American and Australian marsupials, UCP1 is exclusively expressed in distinct adipose tissue sites and appears to be recruited by cold exposure in the smallest species under investigation (Sminthopsis crassicaudata). Our data suggest that an archetypal brown adipose tissue was present at least 150 million yr ago allowing early mammals to produce endogenous heat in the cold, without dependence on shivering and locomotor activity.
