Nicotinamide mononucleotide induces lipolysis by regulating ATGL expression via the SIRT1-AMPK axis in adipocytes.
Nicotinamide mononucleotide induces lipolysis by regulating ATGL expression via the SIRT1-AMPK axis in adipocytes.
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DOI：
10.1016/j.bbrep.2023.101476
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发表时间：
2023-07
影响因子：
2.7
通讯作者：
Hosooka, Tetsuya
中科院分区：
文献类型：
--
作者：
Imi, Yukiko;Amano, Reina;Kasahara, Nanaho;Obana, Yuichiro;Hosooka, Tetsuya
烟酰胺腺嘌呤二核苷酸（NAD+）依赖性蛋白脱乙酰酶SIRT 1在代谢调节中起重要作用。尽管给予烟酰胺单甘肽（NMN）（一种关键的NAD+中间体）已显示可改善代谢紊乱，如胰岛素抵抗和葡萄糖耐受不良，但NMN对脂肪细胞中脂质代谢调节的直接影响仍不清楚。我们在此研究了NMN对3 T3-L1分化脂肪细胞中脂质储存的影响。油红O染色显示NMN处理减少了这些细胞中的脂质积累。发现NMN增强脂肪细胞中的脂解，因为NMN处理增加了培养基中甘油的浓度。Western blotting和real-time RT-PCR分析显示，NMN处理后3 T3-L1脂肪细胞中脂肪甘油三酯脂酶（ATGL）在蛋白和mRNA水平的表达均增加。而NMN增加SIRT 1表达和AMPK活化，AMPK抑制剂化合物C恢复了这些细胞中ATGL表达的NMN依赖性上调，表明NMN通过SIRT 1-AMPK轴上调ATGL表达。NMN给药显著降低了高脂饮食小鼠的皮下脂肪量。我们还发现，皮下脂肪中的脂肪细胞的大小与NMN治疗减少。与脂肪质量和脂肪细胞大小的改变一致，皮下脂肪中的ATGL表达随着NMN处理而略微增加，尽管显著。这些结果表明，NMN抑制饮食诱导的肥胖小鼠的皮下脂肪量，可能部分通过上调ATGL。出乎意料的是，在附睾脂肪中未观察到NMN处理的脂肪量减少以及ATGL上调，这意味着NMN的作用在脂肪组织中具有位点特异性。因此，这些发现为NMN/NAD+在代谢调节中的机制提供了重要的见解。NMN通过增加3 T3-L1脂肪细胞中的ATGL表达来诱导脂解。NMN通过SIRT 1/AMPK轴增强3 T3-L1脂肪细胞ATGL表达。NMN通过抑制脂肪细胞肥大改善小鼠饮食诱导的肥胖。
Nicotinamide adenine dinucleotide (NAD+) -dependent protein deacetylase SIRT1 plays an important role in the regulation of metabolism. Although the administration of nicotinamide mononucleotide (NMN), a key NAD+ intermediate, has been shown to ameliorate metabolic disorders, such as insulin resistance and glucose intolerance, the direct effect of NMN on the regulation of lipid metabolism in adipocytes remains unclear. We here investigated the effect of NMN on lipid storage in 3T3-L1 differentiated adipocytes. Oil-red O staining showed that NMN treatment reduced lipid accumulation in these cells. NMN was found to enhance lipolysis in adipocytes since the concentration of glycerol in the media was increased by NMN treatment. Western blotting and real-time RT-PCR analysis revealed that adipose triglyceride lipase (ATGL) expression at both protein and mRNA level was increased with NMN treatment in 3T3-L1 adipocytes. Whereas NMN increased SIRT1 expression and AMPK activation, an AMPK inhibitor compound C restored the NMN-dependent upregulation of ATGL expression in these cells, suggesting that NMN upregulates ATGL expression through the SIRT1-AMPK axis. NMN administration significantly decreased subcutaneous fat mass in mice on a high-fat diet. We also found that adipocyte size in subcutaneous fat was decreased with NMN treatment. Consistent with the alteration of fat mass and adipocyte size, the ATGL expression in subcutaneous fat was slightly, albeit significantly, increased with NMN treatment. These results indicate that NMN suppresses subcutaneous fat mass in diet-induced obese mice, potentially in part via the upregulation of ATGL. Unexpectedly, the reduction in fat mass as well as ATGL upregulation with NMN treatment were not observed in epididymal fat, implying that the effects of NMN are site-specific in adipose tissue. Thus, these findings provide important insights into the mechanism of NMN/NAD+ in the regulation of metabolism. NMN induces lipolysis by increasing ATGL expression in 3T3-L1 adipocytes. NMN enhances ATGL expression through SIRT1/AMPK axis in 3T3-L1 adipocytes. NMN ameliorates diet-induced obesity in mice by suppressing adipocyte hypertrophy.
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影响因子：
2.4
作者：
Imi Y;Yabiki N;Abuduli M;Masuda M;Yamanaka-Okumura H;Taketani Y
通讯作者：
Taketani Y
影响因子：
6.5
作者：
Gaidhu, Mandeep P.;Fediuc, Sergiu;Ceddia, Rolando B.
通讯作者：
Ceddia, Rolando B.
影响因子：
56.9
作者：
Haemmerle, G;Lass, A;Zechner, R
通讯作者：
Zechner, R
影响因子：
6.1
作者：
Jiang, Zhihao;Wang, Huihui;Ma, Haitian
通讯作者：
Ma, Haitian
DOI：
10.1155/2015/298635
发表时间：
2015
期刊：
Evidence-based complementary and alternative medicine : eCAM
影响因子：
--
作者：
Liou CJ;Lai XY;Chen YL;Wang CL;Wei CH;Huang WC
通讯作者：
Huang WC