CGL type 2 is a rare autosomal recessive syndrome characterized by an almost complete lack of body fat. CGL is caused by loss-of-function mutations in both alleles of the BSCL2 gene that codifies to seipin. Subjects often show hyperglycemia, decreased HDL-c, and hypoadiponectinemia. These laboratory findings are important triggers for changes in redox and ER homeostasis. Therefore, our aim was to investigate whether these intracellular mechanisms are associated with this syndrome. We collected blood from people from Northeastern Brazil with 0, 1, and 2 mutant alleles for the rs786205071 in the BSCL2 gene. Through the qPCR technique, we evaluated the expression of genes responsible for triggering the antioxidant response, DNA repair, and ER stress in leukocytes. Colorimetric tests were applied to quantify lipid peroxidation and to evaluate the redox status of glutathione, as well as to access the panorama of energy metabolism. Long extension PCR was performed to observe leukocyte mitochondrial DNA lesions, and the immunoblot technique to investigate plasma adiponectin concentrations. Subjects with the rs786205071 in both BSCL2 alleles showed increased transcription of NFE2L2, APEX1, and OGG1 in leukocytes, as well as high concentrations of malondialdehyde and the GSSG:GSH ratio in plasma. We also observed increase of mitochondrial DNA lesions and XBP1 splicing, as well as a decrease in adiponectin and HDL-c. Our data suggest the presence of lipid lesions due to changes in redox homeostasis in that group, associated with increased levels of mitochondrial DNA damage and transcriptional activation of genes involved with antioxidant response and DNA repair.

中文翻译：

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氧化还原和内质网稳态的变化与2型先天性全身性脂肪营养不良有关。

CGL 2型是一种罕见的常染色体隐性遗传综合症，其特征是体内脂肪几乎完全缺乏。CGL是由BSCL2基因的两个等位基因中的功能缺失突变引起的，后者编码为seipin。受试者经常表现出高血糖，HDL-c降低和脂联素低血症。这些实验室发现是氧化还原和内质网稳态改变的重要诱因。因此，我们的目的是研究这些细胞内机制是否与此综合征相关。我们从BSCL2基因中的rs786205071的巴西东北部人群中抽取了0、1和2个突变等位基因。通过qPCR技术，我们评估了白细胞中负责触发抗氧化反应，DNA修复和内质网应激的基因表达。比色法用于定量脂质过氧化和评估谷胱甘肽的氧化还原状态，以及进入能量代谢的全景。进行长延伸PCR以观察白细胞线粒体DNA损伤，并通过免疫印迹技术研究血浆脂联素浓度。在两个BSCL2等位基因中都具有rs786205071的受试者显示白细胞中NFE2L2，APEX1和OGG1的转录增加，以及血浆中的高丙二醛和GSSG：GSH比。我们还观察到线粒体DNA损伤和XBP1剪接的增加，以及脂联素和HDL-c的减少。我们的数据表明，该组中存在由于氧化还原稳态改变而引起的脂质损伤，