Leonardo C Ferreira, Josivan G Lima, Carolina O Mendes-Aguiar, Francisco P Freire-Neto, Paulo R P Nascimento, Glória R G Monteiro, Selma M B Jeronimo
{"title":"The blood transcriptome of the human congenital generalized lipodystrophy.","authors":"Leonardo C Ferreira, Josivan G Lima, Carolina O Mendes-Aguiar, Francisco P Freire-Neto, Paulo R P Nascimento, Glória R G Monteiro, Selma M B Jeronimo","doi":"10.1007/s12020-025-04257-0","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a recessive genetic disease. Affected individuals present musculoskeletal abnormalities, insulin resistance, hepatic steatosis, and may develop cardiomyopathy and mental retardation The mechanism linking AGPAT2 (for CGL1) and BSCL2 (for CGL2) mutations to the syndrome has yet to be fully understood.</p><p><strong>Methods: </strong>Here, we analyzed blood cell transcriptomes from individuals with CGL1 (n = 3), CGL2 (n = 12), unaffected BSCL2 heterozygotes (HET, n = 8), and healthy individuals (CTRL, n = 3). Study participants were also evaluated by densitometry (GE Lunar DPX), in addition to biochemical panel and pro-inflammatory cytokines measured in serum.</p><p><strong>Results: </strong>The gene expression profile of CGL1 was similar to CTRL, a result likely due to the compensatory activity of other AGPAT isoforms. CGL2 had 283 differentially expressed genes (DEGs), most enriched for neurodegenerative- and mitochondria-related genes. There was a negative correlation between the top1 gene, NUAK2, and fat mass (rho = -0.55, p = 0.01). The HET group had 105 DEGs, with OLR1, an atherogenic gene, as the most significant (P<sub>adj</sub> = 0.003). Up-regulation of TNF signaling pathway was also detected, a finding confirmed by high TNF and low IL10 levels in serum.</p><p><strong>Conclusion: </strong>Both CGL2 individuals and their unaffected relatives had abnormal gene expression pattern. Further epidemiological studies should seek to assess cardiovascular risk in heterozygote individuals.</p>","PeriodicalId":49211,"journal":{"name":"Endocrine","volume":" ","pages":""},"PeriodicalIF":3.0000,"publicationDate":"2025-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Endocrine","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12020-025-04257-0","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Congenital generalized lipodystrophy (CGL), also known as Berardinelli-Seip syndrome, is a recessive genetic disease. Affected individuals present musculoskeletal abnormalities, insulin resistance, hepatic steatosis, and may develop cardiomyopathy and mental retardation The mechanism linking AGPAT2 (for CGL1) and BSCL2 (for CGL2) mutations to the syndrome has yet to be fully understood.
Methods: Here, we analyzed blood cell transcriptomes from individuals with CGL1 (n = 3), CGL2 (n = 12), unaffected BSCL2 heterozygotes (HET, n = 8), and healthy individuals (CTRL, n = 3). Study participants were also evaluated by densitometry (GE Lunar DPX), in addition to biochemical panel and pro-inflammatory cytokines measured in serum.
Results: The gene expression profile of CGL1 was similar to CTRL, a result likely due to the compensatory activity of other AGPAT isoforms. CGL2 had 283 differentially expressed genes (DEGs), most enriched for neurodegenerative- and mitochondria-related genes. There was a negative correlation between the top1 gene, NUAK2, and fat mass (rho = -0.55, p = 0.01). The HET group had 105 DEGs, with OLR1, an atherogenic gene, as the most significant (Padj = 0.003). Up-regulation of TNF signaling pathway was also detected, a finding confirmed by high TNF and low IL10 levels in serum.
Conclusion: Both CGL2 individuals and their unaffected relatives had abnormal gene expression pattern. Further epidemiological studies should seek to assess cardiovascular risk in heterozygote individuals.
期刊介绍：
Well-established as a major journal in today’s rapidly advancing experimental and clinical research areas, Endocrine publishes original articles devoted to basic (including molecular, cellular and physiological studies), translational and clinical research in all the different fields of endocrinology and metabolism. Articles will be accepted based on peer-reviews, priority, and editorial decision. Invited reviews, mini-reviews and viewpoints on relevant pathophysiological and clinical topics, as well as Editorials on articles appearing in the Journal, are published. Unsolicited Editorials will be evaluated by the editorial team. Outcomes of scientific meetings, as well as guidelines and position statements, may be submitted. The Journal also considers special feature articles in the field of endocrine genetics and epigenetics, as well as articles devoted to novel methods and techniques in endocrinology.
Endocrine covers controversial, clinical endocrine issues. Meta-analyses on endocrine and metabolic topics are also accepted. Descriptions of single clinical cases and/or small patients studies are not published unless of exceptional interest. However, reports of novel imaging studies and endocrine side effects in single patients may be considered. Research letters and letters to the editor related or unrelated to recently published articles can be submitted.
Endocrine covers leading topics in endocrinology such as neuroendocrinology, pituitary and hypothalamic peptides, thyroid physiological and clinical aspects, bone and mineral metabolism and osteoporosis, obesity, lipid and energy metabolism and food intake control, insulin, Type 1 and Type 2 diabetes, hormones of male and female reproduction, adrenal diseases pediatric and geriatric endocrinology, endocrine hypertension and endocrine oncology.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
