MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice
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MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice. / Fang, Shu; Feng, Jie; Zhang, Hongbin; Li, Ping; Zhang, Yudan; Zeng, Yanmei; Cai, Yingying; Lin, Xiaochun; Xue, Yaoming; Guan, Meiping.
In: Adipocyte, Vol. 9, No. 1, 2020, p. 179-188.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - MiR-455 targeting SOCS3 improve liver lipid disorders in diabetic mice
AU - Fang, Shu
AU - Feng, Jie
AU - Zhang, Hongbin
AU - Li, Ping
AU - Zhang, Yudan
AU - Zeng, Yanmei
AU - Cai, Yingying
AU - Lin, Xiaochun
AU - Xue, Yaoming
AU - Guan, Meiping
PY - 2020
Y1 - 2020
N2 - MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACCα) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)-stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACCα. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3.
AB - MiR-455 has been verified a key regulator of brown adipose tissue and adipose tissue-specific overexpression of miR-455 (ap2-miR-455) mice could combat high-fat-diet-induced obesity. This study is to verify overexpression of miR-455 could ameliorate the lipid accumulation and metabolism in the liver of db/db diabetic mice and explore the potential mechanisms. Diabetic mice (db/db) and control mice (db/m) were randomly divided into four groups. After overexpression of miR-455 in the liver of db/db mice, the triglycerides level in both serum and liver decreased, the lipid deposit in liver was improved, the expression of fatty acid synthase, stearoyl-CoA desaturase 1, sterol regulatory element binding protein 1c (SREBP-1c) and acetyl-CoA carboxylase (ACCα) was also significantly down-regulated. TargetScan indicated that suppressor of cytokine signalling 3 (SOCS3) is predicated to target miR-455 and the protein of SOCS3 in the liver of db/db mice after intervention was significantly decreased. The dual luciferase reporter assay showed that SOCS3 was target gene of miR-455. In vitro, in Palmitate (PA)-stimulated human normal liver (LO2) cells, transfected miR-455 mimic could significantly inhibit the expression of SOCS3, while transfected miR-455 inhibitor could up-regulate the expression of SOCS3. Transfecting LO2 cells with siRNA of SOCS3 could significantly down-regulate the protein expression of SREBP-1c and ACCα. Our study showed that overexpression of miR-455 in the liver could improve lipid metabolism in diabetic mice by down-regulating its target gene SOCS3.
KW - Diabetes
KW - lipid metabolism
KW - miR-455
KW - NAFLD
KW - SOCS3
UR - http://www.scopus.com/inward/record.url?scp=85083498201&partnerID=8YFLogxK
U2 - 10.1080/21623945.2020.1749495
DO - 10.1080/21623945.2020.1749495
M3 - Journal article
C2 - 32272865
AN - SCOPUS:85083498201
VL - 9
SP - 179
EP - 188
JO - Adipocytes
JF - Adipocytes
SN - 1550-2082
IS - 1
ER -
ID: 247037894