Dual Effects of Metformin on Adipogenic Differentiation of 3T3-L1 Preadipocyte in AMPK-Dependent and Independent Manners.
Dual Effects of Metformin on Adipogenic Differentiation of 3T3-L1 Preadipocyte in AMPK-Dependent and Independent Manners.
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二甲双胍对 3T3-L1 前脂肪细胞以 AMPK 依赖和独立方式成脂分化的双重作用。
DOI：
10.3390/ijms19061547
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发表时间：
2018-05-23
影响因子：
5.6
通讯作者：
Wang X
中科院分区：
文献类型：
--
作者：
Chen D;Wang Y;Wu K;Wang X
据报道，二甲双胍在治疗2型糖尿病时具有降低体重的作用。然而，有限的研究检查了二甲双胍对体外脂肪形成的影响，现有数据不确定且相互矛盾。在这项研究中，我们研究了不同浓度的二甲双胍对3 T3-L1前脂肪细胞脂肪细胞分化的影响，发现二甲双胍对脂肪形成具有双重作用。在3 T3-L1细胞中，较低浓度（1.25-2.5 mM）的二甲双胍显著诱导脂肪生成，而较高浓度（5-10 mM）的二甲双胍显著抑制脂肪生成。不同剂量二甲双胍对脂肪生成的双相效应伴随着脂肪生成和脂肪生成基因表达的增加或减少，包括过氧化物酶体增殖物激活受体（PPARγ）、CCAAT/增强子结合蛋白α（C/EBPα）和脂肪酸合成酶（FXR）在信使RNA（mRNA）和蛋白水平上的表达。此外，仅较高浓度的二甲双胍诱导腺苷5′-单磷酸（AMP）活化蛋白激酶（AMPK）、p38和c-Jun N-末端激酶（JNK）的磷酸化，并降低细胞外调节蛋白激酶（ERK）和Akt的磷酸化。用化合物C（一种特异性AMPK抑制剂）预处理显著对抗高浓度二甲双胍诱导的脂肪生成抑制。总之，这些结果表明二甲双胍对脂肪细胞分化的影响是双相的，具有剂量依赖性。较低浓度的二甲双胍可诱导脂肪生成，这可能以AMPK非依赖性方式介导，而较高浓度的二甲双胍可通过AMPK激活抑制脂肪生成。
Metformin has been reported to have body weight lowering effects while treating type 2 diabetes. However, limited studies examined the effects of metformin on adipogenesis in vitro, and available data are inconclusive and contradictory. In this study, we examined the effects of a variety of concentrations of metformin on adipocyte differentiation of 3T3-L1 preadipocytes and found metformin exhibits a dual effect on adipogenesis. Metformin at lower concentrations (1.25–2.5 mM) significantly induced adipogenesis while at higher concentrations (5–10 mM) metformin significantly inhibited adipogenesis in 3T3-L1 cells. The biphasic effect of different doses of metformin on adipogenesis was accompanied by increasing or decreasing the expression of adipogenic and lipogenic genes including peroxisome proliferator-activated receptor (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), and fatty acid synthase (FASN) at both messenger RNA (mRNA) and protein levels. Furthermore, only the higher concentrations of metformin induced the phosphorylation of adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK), p38, and c-Jun N-terminal kinase (JNK) and reduced the phosphorylation of extracellular regulated protein kinases (ERK) and Akt. Pretreatment with compound C, a specific AMPK inhibitor, significantly countered high concentration of metformin-induced inhibition of adipogenesis. Taken together, these findings demonstrate that the effect of metformin on adipocyte differentiation is biphasic and dose-dependent. Lower concentrations of metformin induce adipogenesis, which could be mediated in an AMPK-independent manner, while higher concentrations of metformin inhibit adipogenesis via AMPK activation.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
影响因子：
4.7
作者：
Dallaglio K;Bruno A;Cantelmo AR;Esposito AI;Ruggiero L;Orecchioni S;Calleri A;Bertolini F;Pfeffer U;Noonan DM;Albini A
通讯作者：
Albini A
DOI：
10.1159/000381643
发表时间：
2015
期刊：
Medical principles and practice : international journal of the Kuwait University, Health Science Centre
影响因子：
--
作者：
Kinaan M;Ding H;Triggle CR
通讯作者：
Triggle CR
影响因子：
4
作者：
Lee, Soo Kyung;Lee, Jung Ok;Kim, Hyeon Soo
通讯作者：
Kim, Hyeon Soo
影响因子：
2.9
作者：
Desilets, Alicia R.;Dhakal-Karki, Sushmita;Dunican, Kaelen C.
通讯作者：
Dunican, Kaelen C.