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Article ; Online: Bidirectional effect of vitamin D on brown adipogenesis of C3H10T1/2 fibroblast-like cells.

Mukai, Takako / Kusudo, Tatsuya

2023 Volume 11, Page(s) e14785

Abstract: Background: Brown adipose tissue (BAT) dissipates caloric energy as heat and plays a role in glucose and lipid metabolism. Therefore, augmentation and activation of BAT are the focus of new treatment strategies against obesity, a primary risk factor of ... ...

Abstract	Background: Brown adipose tissue (BAT) dissipates caloric energy as heat and plays a role in glucose and lipid metabolism. Therefore, augmentation and activation of BAT are the focus of new treatment strategies against obesity, a primary risk factor of metabolic syndrome. The vitamin D system plays a crucial role in mineral homeostasis, bone metabolism, and cell proliferation and differentiation. In this study, we investigated the effects of vitamin D Methods: The mouse fibroblast-like cell line C3H10T1/2 was differentiated into brown adipocytes in the presence of 1,25(OH) Results: 1,25(OH) Conclusion: These data indicate the potential of vitamin D and its analogs as therapeutics for the treatment of obesity and related metabolic diseases.
MeSH term(s)	Mice ; Animals ; Adipogenesis ; Vitamin D ; Vitamins/pharmacology ; Obesity ; Fibroblasts
Chemical Substances	Vitamin D (1406-16-2) ; Vitamins
Language	English
Publishing date	2023-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2703241-3
ISSN	2167-8359 ; 2167-8359
ISSN (online)	2167-8359
ISSN	2167-8359
DOI	10.7717/peerj.14785
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Bidirectional effect of vitamin D on brown adipogenesis of C3H10T1/2 fibroblast-like cells

Takako Mukai / Tatsuya Kusudo

PeerJ, Vol 11, p e

2023 Volume 14785

Abstract: Background Brown adipose tissue (BAT) dissipates caloric energy as heat and plays a role in glucose and lipid metabolism. Therefore, augmentation and activation of BAT are the focus of new treatment strategies against obesity, a primary risk factor of ... ...

Abstract	Background Brown adipose tissue (BAT) dissipates caloric energy as heat and plays a role in glucose and lipid metabolism. Therefore, augmentation and activation of BAT are the focus of new treatment strategies against obesity, a primary risk factor of metabolic syndrome. The vitamin D system plays a crucial role in mineral homeostasis, bone metabolism, and cell proliferation and differentiation. In this study, we investigated the effects of vitamin D3 [1,25(OH)2D3] on brown adipocyte differentiation. Methods The mouse fibroblast-like cell line C3H10T1/2 was differentiated into brown adipocytes in the presence of 1,25(OH)2D3. The effect of 1,25(OH)2D3 on brown adipocyte differentiation was assessed by measuring lipid accumulation, the expression of related genes, and cytotoxicity. The viability of C3H10T1/2 cells was measured using the Cell Counting Kit-8 assay. Gene expression was investigated using quantitative reverse transcription-polymerase chain reaction. Protein expression was estimated using western blotting. Results 1,25(OH)2D3 inhibited adipocyte differentiation and exerted a cytotoxic effect at 1 nM. However, in the physiological concentration range (50–250 pM), 1,25(OH)2D3 promoted uncoupling protein 1 (UCP1) expression in C3H10T1/2 cells. This effect was not observed when 1,25(OH)2D3 was added 48 h after the initiation of differentiation, suggesting that the vitamin D system acts in the early phase of the differentiation program. We showed that 1,25(OH)2D3 increased the expression of two key regulators of brown adipogenesis, PR domain containing 16 (Prdm16) and peroxisome proliferator-activated receptor γ coactivator-1α (Pgc1α). Furthermore, 1,25(OH)2D3 increased Ucp1 expression in 3T3-L1 beige adipogenesis in a dose-dependent manner. Conclusion These data indicate the potential of vitamin D and its analogs as therapeutics for the treatment of obesity and related metabolic diseases.
Keywords	Vitamin D ; Brown adipocyte ; BAT ; C3H10T1/2 ; 3T3-L1 ; Medicine ; R ; Biology (General) ; QH301-705.5
Subject code	616
Language	English
Publishing date	2023-01-01T00:00:00Z
Publisher	PeerJ Inc.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Consideration on size, velocity and path of droplets emitted during running.

Kuroki, Takako / Momma, Reiko / Hoshi, Daisuke / Hong, Sungchan / Hizawa, Nobuyuki / Mukai, Naoki / Watanabe, Koichi / Okamoto, Yoshikazu

The Journal of sports medicine and physical fitness

2023 Volume 63, Issue 10, Page(s) 1100–1117

Abstract: Background: People began to wear face masks during physical activities due to spread of COVID-19. There are no previous studies about the need for wearing masks while running.: Methods: Assuming a citizen runner who runs full marathon in 4 hours, we ... ...

Abstract	Background: People began to wear face masks during physical activities due to spread of COVID-19. There are no previous studies about the need for wearing masks while running. Methods: Assuming a citizen runner who runs full marathon in 4 hours, we verified the path and the amount of droplet dispersal, setting a humanoid mannequin with a mask in simulated running environment (Experiment 1). We also had six adults exercise in the same environment to examine droplet behaviors when not wearing a face mask (Experiment 2). Average droplet size was determined, and repeated measures ANOVA was carried out to examine statistical significance. To evaluate observed droplet behaviors, theoretical solutions of the downfall motion of large droplets were then derived, taking air resistance into consideration. Results: Experiment 1: wearing a face mask caused more droplets to adhere to the face; Experiment 2: droplets were emitted in conversation, coughing or sneezing, and they fell within social distancing. Average droplet size was not sensitive to the wind velocity. It could vary with a significant difference for time and wind velocity. Observed velocity and path of droplet can be expressed by the theoretical solutions. Conclusions: Velocity and path of large droplets can be expressed by the theoretical solution of particles in downfall motion under air resistance. We therefore conclude that wearing a mask while running gives adverse effects in preventing infection. Possibility of droplet transmission while running is considered low even when not wearing a face mask, as long as social distancing is ensured.
MeSH term(s)	Adult ; Humans ; COVID-19/prevention & control ; Masks ; Physical Distancing ; Running
Language	English
Publishing date	2023-07-10
Publishing country	Italy
Document type	Journal Article
ZDB-ID	410823-1
ISSN	1827-1928 ; 0022-4707
ISSN (online)	1827-1928
ISSN	0022-4707
DOI	10.23736/S0022-4707.23.14923-1
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Article ; Online: Spatially restricted substrate-binding site of cortisol-synthesizing CYP11B1 limits multiple hydroxylations and hinders aldosterone synthesis.

Mukai, Kuniaki / Sugimoto, Hiroshi / Kamiya, Katsumasa / Suzuki, Reiko / Matsuura, Tomomi / Hishiki, Takako / Shimada, Hideo / Shiro, Yoshitsugu / Suematsu, Makoto / Kagawa, Norio

Current research in structural biology

2021 Volume 3, Page(s) 192–205

Abstract: Human cytochromes ... ...

Abstract	Human cytochromes P450
Language	English
Publishing date	2021-08-26
Publishing country	Netherlands
Document type	Journal Article
ISSN	2665-928X
ISSN (online)	2665-928X
DOI	10.1016/j.crstbi.2021.08.001
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Article ; Online: CREG1 stimulates brown adipocyte formation and ameliorates diet-induced obesity in mice.

Hashimoto, Michihiro / Kusudo, Tatsuya / Takeuchi, Tamaki / Kataoka, Naoya / Mukai, Takako / Yamashita, Hitoshi

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2019 Volume 33, Issue 7, Page(s) 8069–8082

Abstract: Increased formation of brown and beige adipocytes is critical for adaptive thermogenesis to maintain homeothermy in cold or to circumvent diet-induced obesity (DIO). Cellular repressor of adenovirus early region 1A-stimulated genes 1 (CREG1) exhibits the ...

Abstract	Increased formation of brown and beige adipocytes is critical for adaptive thermogenesis to maintain homeothermy in cold or to circumvent diet-induced obesity (DIO). Cellular repressor of adenovirus early region 1A-stimulated genes 1 (CREG1) exhibits the ability to stimulate brown adipogenesis, including the induction of uncoupling protein 1 (UCP1),
MeSH term(s)	Adipocytes, Brown/metabolism ; Adipocytes, Brown/pathology ; Adipose Tissue, Brown/metabolism ; Adipose Tissue, Brown/pathology ; Animals ; Diet, High-Fat/adverse effects ; Mice ; Mice, Knockout ; Mice, Transgenic ; Obesity/chemically induced ; Obesity/genetics ; Obesity/metabolism ; Obesity/pathology ; Repressor Proteins/genetics ; Repressor Proteins/metabolism ; Thermogenesis ; Uncoupling Protein 1/biosynthesis
Chemical Substances	Creg protein, mouse ; Repressor Proteins ; Ucp1 protein, mouse ; Uncoupling Protein 1
Language	English
Publishing date	2019-03-27
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.201802147RR
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Article ; Online: Spatially restricted substrate-binding site of cortisol-synthesizing CYP11B1 limits multiple hydroxylations and hinders aldosterone synthesis

Kuniaki Mukai / Hiroshi Sugimoto / Katsumasa Kamiya / Reiko Suzuki / Tomomi Matsuura / Takako Hishiki / Hideo Shimada / Yoshitsugu Shiro / Makoto Suematsu / Norio Kagawa

Current Research in Structural Biology, Vol 3, Iss , Pp 192-

2021 Volume 205

Abstract: Human cytochromes P45011β (CYP11B1) and P450aldo (CYP11B2) are monooxygenases that synthesize cortisol through steroid 11β-hydroxylation and aldosterone through a three-step process comprising 11β-hydroxylation and two 18-hydroxylations, respectively. ... ...

Abstract	Human cytochromes P45011β (CYP11B1) and P450aldo (CYP11B2) are monooxygenases that synthesize cortisol through steroid 11β-hydroxylation and aldosterone through a three-step process comprising 11β-hydroxylation and two 18-hydroxylations, respectively. CYP11B1 also catalyzes 18-monohydroxylation and 11β,18-dihydroxylation. To study the molecular basis of such catalytic divergence of the two enzymes, we examined a CYP11B1 mutant (Mt-CYP11B1) with amino acid replacements on the distal surface by determining the catalytic activities and crystal structure in the metyrapone-bound form at 1.4-Å resolution. Mt-CY11B1 retained both 11β-hydroxylase and 18-hydroxylase activities of the wild type (Wt-CYP11B1) but lacked 11β,18-dihydroxylase activity. Comparisons of the crystal structure of Mt-CYP11B1 to those of Wt-CYP11B1 and CYP11B2 that were already reported show that the mutation reduced the innermost space putatively surrounding the C3 side of substrate 11-deoxycorticosterone (DOC) bound to Wt-CYP11B1, while the corresponding space in CYP11B2 is enlarged markedly and accessible to bulk water through a channel. Molecular dynamics simulations of their DOC-bound forms supported the above findings and revealed that the enlarged space of CYP11B2 had a hydrogen bonding network involving water molecules that position DOC. Thus, upon positioning 11β-hydroxysteroid for 18-hydroxylation in their substrate-binding sites, steric hindrance could occur more strongly in Mt-CYP11B1 than in Wt-CYP11B1 but less in CYP11B2. Our investigation employing Mt-CYP11B1 sheds light on the divergence in structure and function between CYP11B1 and CYP11B2 and suggests that CYP11B1 with spatially-restricted substrate-binding site serves as 11β-hydroxylase, while CYP11B2 with spatially-extended substrate-binding site successively processes additional 18-hydroxylations to produce aldosterone.
Keywords	Adrenal ; Cytochrome P450 ; Molecular dynamics ; Steroid hormone ; X-ray crystallography ; Biology (General) ; QH301-705.5
Subject code	500
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Elsevier
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Silencing of FABP1 ameliorates hepatic steatosis, inflammation, and oxidative stress in mice with nonalcoholic fatty liver disease.

Mukai, Takako / Egawa, Miki / Takeuchi, Tamaki / Yamashita, Hitoshi / Kusudo, Tatsuya

FEBS open bio

2017 Volume 7, Issue 7, Page(s) 1009–1016

Abstract: Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide and has been identified as a risk factor for cirrhosis and hepatocellular carcinoma. However, there is no effective pharmacologic treatment for NAFLD. FABP1 is a liver- ... ...

Abstract	Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide and has been identified as a risk factor for cirrhosis and hepatocellular carcinoma. However, there is no effective pharmacologic treatment for NAFLD. FABP1 is a liver-specific fatty acid-binding protein (FABP) that plays important roles in intracellular lipid metabolism in the liver. We investigated the effect of repression of FABP1 expression on NAFLD, using adenovirus-mediated silencing of FABP1. FABP1 knockdown in the liver decreased the liver weight and hepatic triglyceride (TG) accumulation. The expression of inflammatory and oxidative stress markers in the liver was also reduced. The level of thiobarbituric acid-reactive substances, a marker of lipid peroxidation, in the liver of FABP1 knockdown mice was significantly decreased. These results suggest that FABP1 reduction in the liver is an effective approach against NAFLD.
Language	English
Publishing date	2017
Publishing country	England
Document type	Journal Article
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.12240
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Article ; Online: Silencing of FABP1 ameliorates hepatic steatosis, inflammation, and oxidative stress in mice with nonalcoholic fatty liver disease

Takako Mukai / Miki Egawa / Tamaki Takeuchi / Hitoshi Yamashita / Tatsuya Kusudo

FEBS Open Bio, Vol 7, Iss 7, Pp 1009-

2017 Volume 1016

Abstract	Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide and has been identified as a risk factor for cirrhosis and hepatocellular carcinoma. However, there is no effective pharmacologic treatment for NAFLD. FABP1 is a liver‐specific fatty acid‐binding protein (FABP) that plays important roles in intracellular lipid metabolism in the liver. We investigated the effect of repression of FABP1 expression on NAFLD, using adenovirus‐mediated silencing of FABP1. FABP1 knockdown in the liver decreased the liver weight and hepatic triglyceride (TG) accumulation. The expression of inflammatory and oxidative stress markers in the liver was also reduced. The level of thiobarbituric acid‐reactive substances, a marker of lipid peroxidation, in the liver of FABP1 knockdown mice was significantly decreased. These results suggest that FABP1 reduction in the liver is an effective approach against NAFLD.
Keywords	FABP1 ; NAFLD ; Biology (General) ; QH301-705.5
Subject code	571
Language	English
Publishing date	2017-07-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Silencing of FABP1 ameliorates hepatic steatosis, inflammation, and oxidative stress in mice with nonalcoholic fatty liver disease

Mukai, Takako / Egawa, Miki / Takeuchi, Tamaki / Yamashita, Hitoshi / Kusudo, Tatsuya

FEBS Open Bio. 2017 July, v. 7, no. 7

2017

Abstract	Nonalcoholic fatty liver disease (NAFLD) is increasing in prevalence worldwide and has been identified as a risk factor for cirrhosis and hepatocellular carcinoma. However, there is no effective pharmacologic treatment for NAFLD. FABP1 is a liver‐specific fatty acid‐binding protein (FABP) that plays important roles in intracellular lipid metabolism in the liver. We investigated the effect of repression of FABP1 expression on NAFLD, using adenovirus‐mediated silencing of FABP1. FABP1 knockdown in the liver decreased the liver weight and hepatic triglyceride (TG) accumulation. The expression of inflammatory and oxidative stress markers in the liver was also reduced. The level of thiobarbituric acid‐reactive substances, a marker of lipid peroxidation, in the liver of FABP1 knockdown mice was significantly decreased. These results suggest that FABP1 reduction in the liver is an effective approach against NAFLD.
Keywords	fatty acid-binding proteins ; fatty liver ; hepatoma ; inflammation ; lipid metabolism ; lipid peroxidation ; liver ; oxidative stress ; risk factors ; triacylglycerols
Language	English
Dates of publication	2017-07
Size	p. 1009-1016.
Publishing place	John Wiley & Sons, Ltd
Document type	Article
Note	JOURNAL ARTICLE
ZDB-ID	2651702-4
ISSN	2211-5463
ISSN	2211-5463
DOI	10.1002/2211-5463.12240
Database	NAL-Catalogue (AGRICOLA)

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Article ; Online: Glycerol kinase stimulates uncoupling protein 1 expression by regulating fatty acid metabolism in beige adipocytes.

Iwase, Mari / Tokiwa, Soshi / Seno, Shigeto / Mukai, Takako / Yeh, Yu-Sheng / Takahashi, Haruya / Nomura, Wataru / Jheng, Huei-Fen / Matsumura, Sigenobu / Kusudo, Tatsuya / Osato, Naoki / Matsuda, Hideo / Inoue, Kazuo / Kawada, Teruo / Goto, Tsuyoshi

The Journal of biological chemistry

2020 Volume 295, Issue 20, Page(s) 7033–7045

Abstract: Browning of adipose tissue is induced by specific stimuli such as cold exposure and consists of up-regulation of thermogenesis in white adipose tissue. Recently, it has emerged as an attractive target for managing obesity in humans. Here, we performed a ... ...

Abstract	Browning of adipose tissue is induced by specific stimuli such as cold exposure and consists of up-regulation of thermogenesis in white adipose tissue. Recently, it has emerged as an attractive target for managing obesity in humans. Here, we performed a comprehensive analysis to identify genes associated with browning in murine adipose tissue. We focused on glycerol kinase (GYK) because its mRNA expression pattern is highly correlated with that of uncoupling protein 1 (UCP1), which regulates the thermogenic capacity of adipocytes. Cold exposure-induced
MeSH term(s)	Adipocytes, Beige/cytology ; Adipocytes, Beige/metabolism ; Animals ; Cold Temperature ; Cyclic AMP/genetics ; Cyclic AMP/metabolism ; Fatty Acids/genetics ; Fatty Acids/metabolism ; Glycerol Kinase/genetics ; Glycerol Kinase/metabolism ; Isoproterenol/pharmacology ; Male ; Mice ; Second Messenger Systems ; Stearoyl-CoA Desaturase/genetics ; Stearoyl-CoA Desaturase/metabolism ; Thermogenesis ; Transcriptional Activation ; Uncoupling Protein 1/biosynthesis ; Uncoupling Protein 1/genetics
Chemical Substances	Fatty Acids ; Ucp1 protein, mouse ; Uncoupling Protein 1 ; Cyclic AMP (E0399OZS9N) ; Scd1 protein, mouse (EC 1.14.19.1) ; Stearoyl-CoA Desaturase (EC 1.14.19.1) ; Glycerol Kinase (EC 2.7.1.30) ; Isoproterenol (L628TT009W)
Language	English
Publishing date	2020-04-09
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1074/jbc.RA119.011658
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