Sirt1 activator induces proangiogenic genes in preadipocytes to rescue insulin resistance in diet-induced obese mice View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-07-27

AUTHORS

Allah Nawaz, Arshad Mehmood, Yukiko Kanatani, Tomonobu Kado, Yoshiko Igarashi, Akiko Takikawa, Seiji Yamamoto, Keisuke Okabe, Takashi Nakagawa, Kunimasa Yagi, Shiho Fujisaka, Kazuyuki Tobe

ABSTRACT

Sirt1 plays an important role in regulating glucose and lipid metabolism in obese animal models. Impaired adipose tissue angiogenesis in the obese state decreases adipogenesis and thereby contributes to glucose intolerance and lipid metabolism. However, the mechanism by which Sirt1 activation affects obesity-associated impairments in angiogenesis in the adipose tissue is not fully understood. Here, we show that SRT1720 treatment induces angiogenic genes in cultured 3T3-L1 preadipocytes and ex vivo preadipocytes. siRNA-mediated knockdown of Sirt1 in 3T3-L1 preadipocytes downregulated angiogenic genes in the preadipocytes. SRT1720 treatment upregulated metabolically favorable genes and reduced inflammatory gene expressions in the adipose tissue of diet-induced obese (DIO) mice. Collectively, these findings suggest a novel role of SRT1720-induced Sirt1 activation in the induction of angiogenic genes in preadipocytes, thereby reducing inflammation and fibrosis in white adipose tissue (WAT) and promoting insulin sensitivity. More... »

PAGES

11370

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-29773-0

DOI

http://dx.doi.org/10.1038/s41598-018-29773-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1105781429

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30054532


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36 schema:description Sirt1 plays an important role in regulating glucose and lipid metabolism in obese animal models. Impaired adipose tissue angiogenesis in the obese state decreases adipogenesis and thereby contributes to glucose intolerance and lipid metabolism. However, the mechanism by which Sirt1 activation affects obesity-associated impairments in angiogenesis in the adipose tissue is not fully understood. Here, we show that SRT1720 treatment induces angiogenic genes in cultured 3T3-L1 preadipocytes and ex vivo preadipocytes. siRNA-mediated knockdown of Sirt1 in 3T3-L1 preadipocytes downregulated angiogenic genes in the preadipocytes. SRT1720 treatment upregulated metabolically favorable genes and reduced inflammatory gene expressions in the adipose tissue of diet-induced obese (DIO) mice. Collectively, these findings suggest a novel role of SRT1720-induced Sirt1 activation in the induction of angiogenic genes in preadipocytes, thereby reducing inflammation and fibrosis in white adipose tissue (WAT) and promoting insulin sensitivity.
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45 SRT1720 treatment
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49 adipogenesis
50 adipose tissue
51 angiogenesis
52 angiogenic genes
53 animal models
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57 favorable genes
58 fibrosis
59 findings
60 gene expression
61 genes
62 glucose
63 impairment
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65 induction
66 inflammation
67 inflammatory gene expression
68 insulin resistance
69 insulin sensitivity
70 intolerance
71 knockdown
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73 lipid metabolism
74 mechanism
75 metabolism
76 mice
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78 novel role
79 obese animal models
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82 obesity-associated impairment
83 preadipocytes
84 proangiogenic genes
85 resistance
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87 sensitivity
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93 vivo
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