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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44 SIRT1 activation
45 SRT1720 treatment
46 activation
47 activator
48 adipogenesis
49 adipose tissue
50 angiogenesis
51 angiogenic genes
52 animal models
53 diet-induced obese mice
54 ex vivo
55 expression
56 favorable genes
57 fibrosis
58 findings
59 gene expression
60 genes
61 glucose
62 impairment
63 important role
64 induction
65 inflammation
66 inflammatory gene expression
67 insulin resistance
68 insulin sensitivity
69 intolerance
70 knockdown
71 knockdown of SIRT1
72 lipid metabolism
73 mechanism
74 metabolism
75 mice
76 model
77 novel role
78 obese animal models
79 obese mice
80 obese state
81 obesity-associated impairment
82 preadipocytes
83 proangiogenic genes
84 resistance
85 role
86 sensitivity
87 siRNA
88 state
89 tissue
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91 treatment
92 vivo
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