Altered Adipose Tissue DNA Methylation Status in Metabolic Syndrome: Relationships Between Global DNA Methylation and Specific Methylation at Adipogenic, Lipid Metabolism and Inflammatory Candidate Genes and Metabolic Variables
JOURNAL OF CLINICAL MEDICINE
Authors: Castellano-Castillo, Daniel; Moreno-Indias, Isabel; Sanchez-Alcoholado, Lidia; Ramos-Molina, Bruno; Alcaide-Torres, Juan; Morcillo, Sonsoles; Ocana-Wilhelmi, Luis; Tinahones, Francisco; Isabel Queipo-Ortuno, Maria; Cardona, Fernando
Abstract
Metabolic syndrome (MetS) has been postulated to increase the risk for type 2 diabetes, cardiovascular disease and cancer. Adipose tissue (AT) plays an important role in metabolic homeostasis, and AT dysfunction has an active role in metabolic diseases. MetS is closely related to lifestyle and environmental factors. Epigenetics has emerged as an interesting landscape to evaluate the possible interconnection between AT and metabolic disease, since it can be modulated by environmental factors and metabolic status. The aim of this study was to determine whether MetS has an impact on the global DNA methylation pattern and the DNA methylation of several genes related to adipogenesis (PPARG, PPARA), lipid metabolism (RXRA, SREBF2, SREBF1, SCD, LPL, LXRb), and inflammation (LRP1 C3, LEP and TNF) in visceral adipose tissue. LPL and TNF DNA methylation values were significantly different in the control-case comparisons, with higher and lower methylation respectively in the MetS group. Negative correlations were found between global DNA methylation (measured by LINE-1 methylation levels) and the metabolic deterioration and glucose levels. There were associations among variables of MetS, BMI, and HOMA-IR with DNA methylation at several CpG positions for the studied genes. In particular, there was a strong positive association between serum triglyceride levels (TG) with PPARA and LPL methylation levels. TNF methylation was negatively associated with the metabolic worsening and could be an important factor in preventing MetS occurrence according to logistic regression analysis. Therefore, global DNA methylation and methylation at specific genes related to adipogenesis, lipid metabolism and inflammation are related to the etiology of MetS and might explain in part some of the features associated to metabolic disorders.
Effect ofINSIG1on the milk fat synthesis of buffalo mammary epithelial cells
JOURNAL OF DAIRY RESEARCH
Authors: Fan, Xinyang; Qiu, Lihua; Teng, Xiaohong; Zhang, Yongyun; Miao, Yongwang
Abstract
We hypothesized that insulin-induced gene 1 (INSIG1) affects milk fat synthesis in buffalo. For this reason, the protein abundance of INSIG1 in the mammary tissue of buffalo during the peak period of lactation and dry-off period was evaluated. The results showed that the expression of INSIG1 at the peak of lactation was lower than that in the dry-off period. To explore the role of INSIG1 in milk fat synthesis, the buffalo mammary epithelial cells (BMECs) were isolated and purified from buffalo mammary tissue, andINSIG1gene were overexpressed and knocked down by constructing the recombinant lentivirus vector ofINSIG1gene and transfecting into BMECs. Results revealed thatINSIG1overexpression decreased the expression ofINSIG2,SREBP,PPARG,SCD,GPAM,DGAT2andAGPAT6, which led to reduction of triglycerides (TAG) content in the cell. In contrast, knockdown ofINSIG1had a positive effect on mRNA expression of the above genes. Overall, the data provide strong support for a key role of INSIG1 in the regulation of milk fat synthesis in BMECs.