Malic Enzyme 1 (ME1) Promotes Adiposity and Hepatic Steatosis and Induces Circulating Insulin and Leptin in Obese Female Mice.
Malic Enzyme 1 (ME1) Promotes Adiposity and Hepatic Steatosis and Induces Circulating Insulin and Leptin in Obese Female Mice.
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DOI：
10.3390/ijms24076613
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发表时间：
2023-04-01
影响因子：
5.6
通讯作者：
Simmen, Rosalia C. M.
中科院分区：
文献类型：
--
作者：
Simmen, Frank A.;Pabona, John Mark P.;Al-Dwairi, Ahmed;Alhallak, Iad;Montales, Maria Theresa E.;Simmen, Rosalia C. M.
关键词：
苹果酸酶1（ME 1）通过催化L-苹果酸脱羧为丙酮酸，以及伴随的NADP还原为NADPH，支持脂肪生成、胆固醇合成和细胞氧化还原电位。我们通过向C57 BL/6野生型（WT）和MOD-1（缺乏ME 1蛋白）雌性小鼠提供致肥胖饮食来检查ME 1对肥胖发展的贡献。肥胖，血清激素水平，脂肪，乳腺，肝脏和小肠的基因表达模式进行了比较后，10周的饮食实验组。相对于WT雌性小鼠，MOD-1雌性小鼠表现出较低的体重和较少的肥胖;降低的胰岛素、瘦素和雌激素浓度;较高的脂联素和孕酮浓度;较小尺寸的乳腺脂肪细胞;和减少的脂肪肝。MOD-1小鼠腹部脂肪中Lep基因的表达减少;乳腺中Lep、Pparg、Klf 9和Acaca基因的表达减少;肝脏中Pparg和Cdkn 1a基因的表达减少;小肠中Tlr 9和Ffar 3基因的表达减少。相比之下，相对于WT小鼠，MOD-1中Cdkn 2a和Lepr基因的肝脏表达增强。结果记录了ME 1在女性肥胖症发展中的综合作用，表明与特定途径/基因的新联系，并进一步支持ME 1治疗肥胖症，糖尿病和脂肪肝疾病的治疗靶向。
Malic Enzyme 1 (ME1) supports lipogenesis, cholesterol synthesis, and cellular redox potential by catalyzing the decarboxylation of L-malate to pyruvate, and the concomitant reduction of NADP to NADPH. We examined the contribution of ME1 to the development of obesity by provision of an obesogenic diet to C57BL/6 wild type (WT) and MOD-1 (lack ME1 protein) female mice. Adiposity, serum hormone levels, and adipose, mammary gland, liver, and small intestine gene expression patterns were compared between experimental groups after 10 weeks on a diet. Relative to WT female mice, MOD-1 female mice exhibited lower body weights and less adiposity; decreased concentrations of insulin, leptin, and estrogen; higher concentrations of adiponectin and progesterone; smaller-sized mammary gland adipocytes; and reduced hepatosteatosis. MOD-1 mice had diminished expression of Lep gene in abdominal fat; Lep, Pparg, Klf9, and Acaca genes in mammary glands; Pparg and Cdkn1a genes in liver; and Tlr9 and Ffar3 genes in the small intestine. By contrast, liver expression of Cdkn2a and Lepr genes was augmented in MOD-1, relative to WT mice. Results document an integrative role for ME1 in development of female obesity, suggest novel linkages with specific pathways/genes, and further support the therapeutic targeting of ME1 for obesity, diabetes, and fatty liver disease.
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影响因子：
8.1
作者：
Cook TM;Gavini CK;Jesse J;Aubert G;Gornick E;Bonomo R;Gautron L;Layden BT;Mansuy-Aubert V
通讯作者：
Mansuy-Aubert V
DOI：
10.1038/s41576-021-00414-z
发表时间：
2022-03
期刊：
Nature reviews. Genetics
影响因子：
--
作者：
Loos RJF;Yeo GSH
通讯作者：
Yeo GSH
影响因子：
4.1
作者：
Lenert ME;Chaparro MM;Burton MD
通讯作者：
Burton MD
DOI：
10.1152/ajpendo.00583.2005
发表时间：
2006-11-01
影响因子：
5.1
作者：
Kondo, Hidehiko;Minegishi, Yoshihiko;Murase, Takatoshi
通讯作者：
Murase, Takatoshi
影响因子：
8
作者：
Lee, Samuel M.;Muratalla, Jose;Cordoba-Chacon, Jose
通讯作者：
Cordoba-Chacon, Jose