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1.
Ryosuke Kida Hirofumi Yoshida Masaru Murakami Mitsuyuki Shirai Osamu Hashimoto Teruo Kawada Tohru Matsui Masayuki Funaba 《Cell biochemistry and function》2016,34(1):34-41
The ingestion of capsaicin, the principle pungent component of red and chili peppers, induces thermogenesis, in part, through the activation of brown adipocytes expressing genes related to mitochondrial biogenesis and uncoupling such as peroxisome proliferator‐activated receptor (Ppar) γ coactivator‐1α (Pgc‐1α) and uncoupling protein 1 (Ucp1). Capsaicin has been suggested to induce the activation of brown adipocytes, which is mediated by the stimulation of sympathetic nerves. However, capsaicin may directly affect the differentiation of brown preadipocytes, brown adipocyte function, or both, through its significant absorption. We herein demonstrated that Trpv1, a capsaicin receptor, is expressed in brown adipose tissue, and that its expression level is increased during the differentiation of HB2 brown preadipocytes. Furthermore, capsaicin induced calcium influx in brown preadipocytes. A treatment with capsaicin in the early stage of brown adipogenesis did not affect lipid accumulation or the expression levels of Fabp4 (a gene expressed in mature adipocytes), Pparγ2 (a master regulator of adipogenesis) or brown adipocyte‐selective genes. In contrast, a treatment with capsaicin in the late stage of brown adipogenesis slightly increased the expression levels of Fabp4, Pparγ2 and Pgc‐1α. Although capsaicin did not affect the basal expression level of Ucp1, Ucp1 induction by forskolin was partially inhibited by capsaicin, irrespective of the dose of capsaicin. The results of the present study suggest the direct effects of capsaicin on brown adipocytes or in the late stage of brown adipogenesis. 相似文献
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Yongguo Li Tobias Fromme Sabine Schweizer Theresa Schöttl Martin Klingenspor 《EMBO reports》2014,15(10):1069-1076
Thermogenesis in brown adipocytes, conferred by mitochondrial uncoupling protein 1 (UCP1), is receiving great attention because metabolically active brown adipose tissue may protect humans from metabolic diseases. In particular, the thermogenic function of brown‐like adipocytes in white adipose tissue, known as brite (or beige) adipocytes, is currently of prime interest. A valid procedure to quantify the specific contribution of UCP1 to thermogenesis is thus of vital importance. Adrenergic stimulation of lipolysis is a common way to activate UCP1. We here report, however, that in this frequently applied setup, taking control over intracellular fatty acid levels is essential for the analysis of thermogenic function in cultured brown and brite adipocytes. By the application of these findings, we demonstrate that UCP1 is functionally thermogenic in intact brite adipocytes and adrenergic UCP1 activation is largely dependent on adipose triglyceride lipase (ATGL) rather than hormone sensitive lipase (HSL). 相似文献
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Hitoshi Ikeda Anna Pastuszko Naohiko Ikegaki Roger H. Kennett David F. Wilson 《Neurochemical research》1994,19(12):1487-1494
In mature cells of the sympathetic nervous system and the adrenal gland, the activity of dihydroxyphenylalanine decarboxylase (DDC) is higher than that of tyrosine hydroxylase and 3,4-dihydroxyphenylalanine (DOPA) does not accumulate in the cells. On the other hand, it is known that in some neuroblastoma cells there is a relative deficiency of DDC, resulting in accumulation and secretion of DOPA. Such a relative deficiency of DDC is a characteristic of neural cells at an early stage of neural crest development, suggesting the neuroblastoma are cells arrested in early neural crest development. If this were the case, it is possible that agents such as retinoic acid (RA) could induce neuroblastoma to differentiate into mature cells with respect to their metabolism of catecholamines. We have measured the effect of RA on the metabolism of DOPA and expression of tyrosine hydroxylase and DDC in human neuroblastoma cell lines, CHP-126, CHP-134, IMR-32, NB-59, and LA-N-5. When the cell cultures were treated with RA, they showed wide variations in response as measured by morphological change, growth inhibition, enzyme activities and DDC, but does not increase DDC relative to tyrosine hydroxylase. It is concluded that RA does not induce biochemical differentiation of the neuroblastoma into mature cells even when there are extensive morphological changes and suppression of growth rate. 相似文献
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Shen CN Marguerie A Chien CY Dickson C Slack JM Tosh D 《Differentiation; research in biological diversity》2007,75(1):62-74
Recent evidence has shown that retinoic acid (RA) signalling is required for early pancreatic development in zebrafish and frog but its role in later development in mammals is less clear cut. In the present study, we determined the effects of RA on the differentiation of the mouse embryonic pancreas. Addition of all-trans retinoic acid (atRA) to embryonic pancreatic cultures induced a number of changes. Branching morphogenesis and exocrine differentiation were suppressed and there was premature formation of endocrine cell clusters (although the total area of beta cells was not different in control and atRA-treated buds). We investigated the mechanism of these changes and found that the premature formation of beta cells was associated with the early expression of high-level Pdx1 in the endocrine cell clusters. In contrast, the suppressive effect of RA on exocrine differentiation may be due to a combination of two mechanisms (i) up-regulation of the extracellular matrix component laminin and (ii) enhancement of apoptosis. We also demonstrate that addition of fibroblast growth factor (FGF)-10 is able to partially prevent apoptosis and rescue exocrine differentiation and branching morphogenesis in atRA-treated cultures but not in mice lacking the FGF receptor 2-IIIb, suggesting the effects of FGF-10 are mediated through this receptor. 相似文献
6.
Zinc attenuation of GDP binding to brown adipocytes mitochondria in genetically obese (ob/ob) mice 总被引:1,自引:0,他引:1
Ming-Der Chen Pi-Yao Lin Piin-Sheng Chen Vie Cheng Wen-Han Lin 《Biological trace element research》1997,57(2):139-145
In this study, we investigate the in vitro effect of zinc addition on guanosine diphosphate (GDP) binding to mitochondria
in brown adipocytes of genetically obese (ob/ob) mice. Interscapular brown adipocytes of male mice (obese; lean) at 4 and
12 wk of age were incubated with 0, 50, 100, or 200 μM zinc sulfate. Mitochondria were then isolated and their GDP binding capacities were measured. The GDP-binding capacities
of ob/ob mice were lower than lean mice, with or without zinc addition, in both age groups (p<0.05). Zinc addition did not
have any significant effect on GDP binding in lean mice. GDP binding decreased with increasing zinc addition in ob/ob mice,
and this attenuation was more predominant in 12-wk old ob/ob mice. Moreover, we found that high magnesium addition (5 mM) increased GDP binding in lean mice, but this effect was not significant in ob/ob mice. This study reveals that brown adipose
tissue thermogenesis in ob/ob mice could be greatly attenuated by zinc addition, suggesting that zinc may play a regulatory
role in obesity. 相似文献
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Sato T Nagafuku M Shimizu K Taira T Igarashi Y Inokuchi J 《Cell biology international》2008,32(11):1397-1404
Visceral adipose tissue, particularly mesenteric adipose tissue, is important in the pathogenesis of metabolic syndrome. Here, we present a physiologically relevant differentiation system of rat mesenteric-stromal vascular cells (mSVC) to mesenteric-visceral adipocytes (mVAC). We optimized the insulin concentration at levels comparable to those in vivo ( approximately 0.85 ng/ml) by including physiological concentrations of IGF-1. We found that the insulin-like growth factor (IGF-1) and insulin worked synergistically, since IGF-1 alone could induce CCAAT/enhancer binding protein alpha (C/EBPalpha) and adipocyte lipid binding protein (aP2) mRNA expression but not lipid droplet accumulation associated with maturation. Using real-time PCR analyses on 180 adipocyte-related genes, we identified a dramatic effect by IGF-1 plus insulin. We also demonstrated the state of insulin resistance at pathologically high insulin concentrations. This culture system will contribute to understanding the physiological differentiation process and the patho/physiology of mVAC. 相似文献
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Wang XJ Chen J Lv ZB Nie ZM Wang D Shen HD Wang XD Wu XF Zhang YZ 《Journal of cellular biochemistry》2007,102(4):970-979
Cellular retinoic acid binding protein (CRABP) is a member of intracellular lipid-binding protein (iLBP), and closely associated with retinoic acid (RA) activity. We have cloned the CRABP gene from silkworm pupae and studied the interaction between Bombyx mori CRABP (BmCRABP) and all-trans retinoic acid (atRA). The MTT assay data indicated that when BmCRABP is overexpressed in Bm5 cells, the cells dramatically resisted to atRA-induced growth inhibition. Conversely, the cells were sensitive to atRA treatment upon knocking down the BmCRABP expression. Subcellular localization revealed that BmCRABP is a cytoplasm protein, even when treated with atRA, the CRABP still remained in the cytoplasm. These data demonstrated that the function of BmCRABP have an effect on the physiological function of atRA. 相似文献
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Masanori Nagai Kiyoshi Tuchiya Hiromi Kojima 《Prostaglandins & other lipid mediators》1996,51(6):377-386
Effects of prostaglandin E2 (PGE1) were examined on the oxygen consumption and intracellular calcium concentration of rat brown adipose tissue (BAT). PGE2 0.1 nM-1 μM increased oxygen consumption of the tissue blocks of BAT, with a maximum 2–13 min after PGE2 administration. PGE2 was most effective at 1 and 10 nM, and the oxygen consumption was elevated for over 40 min. Pretreatment of BAT with indomethacin, a prostaglandin synthesis inhibitor, did not affect the increase in oxygen consumption induced by noradrenaline. PGE2 at 1–10 nM gradually increased the intracellular calcium concentration of freshly dispersed single brown adipocytes by 3–4 times in 30 min. PGE2 also increased the intracellular calcium concentration of brown adipocytes in calcium-free medium. These results raise the possibility that PGE2 and noradrenaline affect heat genesis and metabolism of BAT independently. 相似文献
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Mammalian adipose tissues are broadly divided into white adipose tissue (WAT) and thermogenic fat tissue (brown adipose tissue and beige adipose tissue). Uncoupling protein 1 (UCP1) is the central protein in thermogenesis, and cells that exhibit induced UCP1 expression and appear scattered throughout WAT are called beige adipocytes, and their induction in WAT is referred to as “beiging”. Beige adipocytes can differentiate from preadipocytes or convert from mature adipocytes. UCP1 was thought to contribute to non-shivering thermogenesis; however, recent studies demonstrated the presence of UCP1-independent thermogenic mechanisms. There is evidence that thermogenic fat tissue contributes to systemic energy expenditure even in human beings. This review discusses the roles that thermogenic fat tissue plays in energy consumption and offers insight into the possibility and challenges associated with its application in the treatment of obesity and type 2 diabetes. 相似文献
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Acylceramides and lanosterol-lipid markers of terminal differentiation in cultured human keratinocytes: Modulating effect of retinoic acid 总被引:1,自引:0,他引:1
J. Brod E. Bavelier P. Justine A. Weerheim M. Ponec 《In vitro cellular & developmental biology. Animal》1991,27(2):163-168
Summary Epidermal differentiation is accompanied by profound changes in the synthesis of a variety of intracellular proteins and intercellular
lipids. In conventional, submerged culture keratinocytes have been shown to lose the ability to synthesize the protein markers
of differentiation. They re-express them, however, when they are cultured in medium supplemented with delipidized [retinoic
acid (RA)-depleted] serum or in air-exposed cultures using de-epidermized dermis (DED) as a substrate. Recent studies have
revealed that acylceramides (AC) and lanosterol (LAN), which are present only in trace amounts in cultures of keratinocytes
grown under submerged conditions on DED in medium supplemented with normal serum, become expressed in significant amounts
when the culture is lifted to the air-liquid interface. Inasmuch as culture conditions may markedly affect the extent of keratinocyte
differentiation, the present study aimed to investigate the effect of normal (RA-containing) or delipidized (RA-depleted)
serum and of RA administration on lipid composition (especially of the AC and LAN contents) in cells cultured under submerged
and air-exposed conditions. To test a possible effect of dermal substrate (used in the air-exposed model), the lipid composition
of keratinocytes grown under submerged conditions on a plastic and on a dermal substrate (de-epidermized dermis, DED) has
also been compared. The results revealed that under all culture conditions, RA deprivation of fetal bovine serum resulted
in a marked increase of total ceramide content. Even under submerged conditions, the presence of both AC and LAN could be
detected. In air-exposed culture, the content of these lipids was markedly increased. Addition of RA at 1 μM concentration to cultures grown in RA-depleted medium induced marked changes in lipid composition under all culture conditions
tested. In cells grown under submerged conditions (both on plastic and on DED) AC and LAN were no longer present in detectable
amounts. Also in air-exposed culture, a marked decrease in the content of these lipids was observed. These results suggest
that liposoluble serum components, like RA, control the synthesis of lipids that are present in later stages of epidermal
differentiation. 相似文献
16.
Regnier Marcelle Darmon Michel 《In vitro cellular & developmental biology. Plant》1989,25(11):1000-1008
Summary It was possible to reconstruct epidermis in vitro by seeding dissociated keratinocytes on de-epidermized dermis and growing
such recombined cultures for 1 wk, exposed to air, at the surface of the culture medium. These conditions were chosen to mimic
the transdermal feeding and the exposure to the atmosphere that occur in vivo. Contrary to classical cultures performed on
plastic dishes covered with culture medium, which show rudimentary differentiation and organization, the architecture of the
stratified epithelium obtained in reconstructed cultures and the distribution of differentiation markers such as suprabasal
keratins, involucrin, and membrane-bound transglutaminase were similar to those of the epidermis of skin biopsies; moreover,
biochemical studies showed that the synthesis of the various keratins and the production of cornified envelopes was similar
to what is found with skin specimens. The reconstructed epidermis model was found to be very useful to study in vitro the
effect of retinoic acid on keratinocyte differentiation and epidermal morphogenesis. 相似文献
17.
Elizabeth Pavez Loriè Hao LiAnders Vahlquist Hans Törmä 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2009,1791(3):220-228
All-trans retinoic acid (RA) levels are controlled by enzymes of the vitamin A metabolism (RDH16, RalDH2, and LRAT) and RA catabolism (CYP26 and CYP2S1). Here, the mRNA expression of these enzymes was investigated in human keratinocytes at different Ca2+concentrations and after exposure to RA and CYP26 inhibitors. Cellular differentiation (high Ca2+) increased the expression of LRAT, RDH16 and RalDH2, and decreased CYP26B1. RA (1 μM) induced CYP26A1, CYP26B1, CYP2S1, CRABPII and LRAT mRNA. The CYP26 inhibitor talarozole altered CYP26A1 and LRAT mRNA expression in a similar way as RA, increased the cellular accumulation of [3H]RA, and induced a punctate CRABPII staining, also observed after siRNA knock-down of CYP26B1 (but not after RA exposure). Furthermore, CYP26B1 siRNA increased the accumulation of [3H]RA and the CRABPII mRNA, suggesting an augmented retinoid signalling. Thus CYP26B1 appears essential for RA catabolism under physiological conditions, whereas CYP26A1 might play a greater role during RA excess. 相似文献
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目的:通过培养3T3-L1前脂肪细胞,并诱导其分化至成熟,研究游离脂肪酸对脂肪细胞糖代谢的影响。方法:培养诱导3T3-L1脂肪细胞,用油红O染色鉴定并比较其形态结构的变化。LPS、EPA、SA、PA干预成熟脂肪细胞,收集不同时间的培养基,葡萄糖氧化酶法算出各组脂肪细胞的葡萄糖消耗量。用Western blot检测不同时间各组干预后细胞AMPK、GLUT4蛋白含量。结果:油红O染色鉴定成熟脂肪细胞胞浆中的脂滴染成红色,并出现戒环样结构;诱导分化第8天,90%以上细胞均分化成熟。含LPS、EPA、SA、PA的培养基作用于成熟脂肪细胞,随着时间的延长,显著抑制脂肪细胞对葡萄糖的吸收(P<0.05),同时,脂肪细胞AMPK、GLUT4蛋白含量在减少(P<0.05)。结论:游离脂肪酸可以诱导胰岛素抵抗的分子机制可能是通过胰岛素信号通路激活蛋白激酶(AMPK),进而影响GLUT4的蛋白表达,使脂肪细胞的葡萄糖吸收率减低,影响脂肪细胞的糖代谢。 相似文献
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Uwe Ramp Claus Dieter Gerharz Edith Eifler Hans Konrad Biesalski Helmut Erich Gabbert 《Biology of the cell / under the auspices of the European Cell Biology Organization》1994,81(1):31-37
Summary— The clonal rat rhabdomyosarcoma cell line BA-HAN-IC is composed of proliferating mononuclear cells, some of which spontaneously fuse to terminally differentiated myotube-like giant cells. This cell line has been shown to be susceptible to differentiation induction with all-trans retinoic acid (RA). Since it is still unknown whether exclusively all-trans RA itself or also its metabolites can act as inductive compounds in our cell line, we exposed BA-HAN-1C cells to the metabolites 4-hydroxy RA, 4-oxo RA and 5,6epoxy RA. Exposure to these RA metabolites resulted in a significant inhibition of proliferation (P < 0.001) and induction of cellular differentiation, as evidenced by a significant increase in the number of myotube-like giant cells (P < 0.05) and a significant increase in creatine kinase activity (P < 0.05). However, differences in the inductive potency of these RA metabolites became apparent. Furthermore, RA metabolites exhibited a significantly weaker (P < 0.05) inductive activity when compared to all-trans RA. Summarizing our results we could demonstrate that the endogenous metabolites 4-hydroxy RA, 4-oxo RA and 5,6-epoxy RA are not merely deactivated cellular excretion products of all-trans RA, but potent inducers of differentiation and inhibitors of proliferation, possibly contributing to the complex physiological actions of retinoic acid. 相似文献