Simmen Frank A, Pabona John Mark P, Al-Dwairi Ahmed, Alhallak Iad, Montales Maria Theresa E, Simmen Rosalia C M
Department of Physiology & Cell Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
The Winthrop P. Rockefeller Cancer Institute, University of Arkansas for Medical Sciences, Little Rock, AR 72205, USA.
Int J Mol Sci. 2023 Apr 1;24(7):6613. doi: 10.3390/ijms24076613.
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 gene in abdominal fat; , , , and genes in mammary glands; and genes in liver; and and genes in the small intestine. By contrast, liver expression of and 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.
苹果酸酶1（ME1）通过催化L-苹果酸脱羧生成丙酮酸，并伴随NADP还原为NADPH，来支持脂肪生成、胆固醇合成和细胞氧化还原电位。我们通过给C57BL/6野生型（WT）和MOD-1（缺乏ME1蛋白）雌性小鼠提供致肥胖饮食，研究了ME1对肥胖发展的作用。在饮食10周后，比较了实验组之间的肥胖程度、血清激素水平以及脂肪组织、乳腺、肝脏和小肠的基因表达模式。相对于WT雌性小鼠，MOD-1雌性小鼠体重较低且肥胖程度较轻；胰岛素、瘦素和雌激素浓度降低；脂联素和孕酮浓度升高；乳腺脂肪细胞尺寸较小；肝脂肪变性减轻。MOD-1小鼠腹部脂肪中 基因的表达减少；乳腺中 、 、 和 基因的表达减少；肝脏中 和 基因的表达减少；小肠中 和 基因的表达减少。相比之下，相对于WT小鼠，MOD-1小鼠肝脏中 和 基因的表达增加。结果证明了ME1在女性肥胖发展中的综合作用，提示了与特定途径/基因的新联系，并进一步支持将ME1作为肥胖、糖尿病和脂肪肝疾病的治疗靶点。
