Abstract Objective Maternal hormonal status can have long-term effects on offspring metabolic health and is likely regulated via epigenetic mechanisms. We elucidated the effects of maternal thyroid hormones on the epigenetic regulation of leptin ( Lep ) transcription in adipose tissue (AT) and subsequently investigated the role of DNA methylation at a Lep upstream enhancer (UE) in adipocyte biology. Results Pregnant mice treated with triiodothyronine (T3) produced offspring with reduced body weight, total fat mass, and gonadal white adipose tissue (gWAT) mass at 6 months of age (treatment: N = 8; control: N = 12). Compared with control offspring, exclusively female offspring of T3-treated mothers presented lower Lep mRNA levels and higher Lep UE methylation in gWAT. In murine preadipocytes, targeted demethylation of the Lep UE via a dCas9-SunTag-TET1 system reduced methylation by ~ 20%, but this effect was insufficient to alter Lep expression or lipid accumulation after differentiation. In human omental visceral AT (OVAT) samples from the Leipzig Obesity BioBank (LOBB, N = 52), LEP UE methylation was associated with body fat percentage, and mediation analysis indicated that leptin serum levels partially mediate this association exclusively in females. Conclusion Findings from the animal model suggest that maternal thyroid hormones influence offspring gWAT Lep expression in a sex-specific manner, potentially through changes in Lep UE methylation. However, in vitro experiments indicate that Lep UE methylation alone is not sufficient to regulate Lep expression or adipocyte lipid accumulation. In humans with obesity, LEP UE methylation is associated with body fat percentage, with leptin serum levels potentially acting as a mediator exclusively in females.
Objective Bacterial translocation to various organs including human adipose tissue (AT) due to increased intestinal permeability remains poorly understood. We hypothesised that: (1) bacterial presence is highly tissue specific and (2) related in composition and quantity to immune inflammatory and metabolic burden. Design We quantified and sequenced the bacterial 16S rRNA gene in blood and AT samples (omental, mesenteric and subcutaneous) of 75 subjects with obesity with or without type 2 diabetes (T2D) and used catalysed reporter deposition (CARD) – fluorescence in situ hybridisation (FISH) to detect bacteria in AT. Results Under stringent experimental and bioinformatic control for contaminants, bacterial DNA was detected in blood and omental, subcutaneous and mesenteric AT samples in the range of 0.1 to 5 pg/µg DNA isolate. Moreover, CARD-FISH allowed the detection of living, AT-borne bacteria. Proteobacteria and Firmicutes were the predominant phyla, and bacterial quantity was associated with immune cell infiltration, inflammatory and metabolic parameters in a tissue-specific manner. Bacterial composition differed between subjects with and without T2D and was associated with related clinical measures, including systemic and tissues-specific inflammatory markers. Finally, treatment of adipocytes with bacterial DNA in vitro stimulated the expression of TNFA and IL6 . Conclusions Our study provides contaminant aware evidence for the presence of bacteria and bacterial DNA in several ATs in obesity and T2D and suggests an important role of bacteria in initiating and sustaining local AT subclinical inflammation and therefore impacting metabolic sequelae of obesity.
Abstract Background Studies on DNA methylation following bariatric surgery have primarily focused on blood cells, while it is unclear to which extend it may reflect DNA methylation profiles in specific metabolically relevant organs such as adipose tissue (AT). Here, we investigated whether adipose tissue depots specific methylation changes after bariatric surgery are mirrored in blood. Methods Using Illumina 850K EPIC technology, we analysed genome-wide DNA methylation in paired blood, subcutaneous and omental visceral AT (SAT/OVAT) samples from nine individuals with severe obesity pre- and post-surgery. Findings The numbers and effect sizes of differentially methylated regions (DMRs) post-bariatric surgery were more pronounced in AT (SAT: 12,865 DMRs from -11.5 to 10.8%; OVAT: 14,632 DMRs from -13.7 to 12.8%) than in blood (9,267 DMRs from -8.8 to 7.7%). Cross-tissue DMRs implicated immune-related genes. Among them, 49 regions could be validated with similar methylation changes in blood from independent individuals. Fourteen DMRs correlated with differentially expressed genes in AT post bariatric surgery, including downregulation of PIK3AP1 in both SAT and OVAT. DNA methylation age acceleration was significantly higher in AT compared to blood, but remained unaffected after surgery. Interpretation Concurrent methylation pattern changes in blood and AT, particularly in immune-related genes, suggest blood DNA methylation mirrors inflammatory state of AT post-bariatric surgery.
The COVID-19 pandemic has sparked discussions about the reasons behind the higher hospitalisation rates among obese individuals. According to initial research findings, adipocytes may play a role in the infection process. We gained further insights by examining 27 paired biopsies of visceral and subcutaneous adipose tissue (AT) from the Leipzig Obesity Biobank (LOBB). The patients were categorised into three groups based on their antibodies against spike and nucleocapsid proteins: control group 1 NN (not infected and not vaccinated), group 2 NV (not infected but vaccinated), and group 3 IV (infected and vaccinated). This categorisation allowed for a comprehensive investigation of the relationship between SARS-CoV-2 infection, adipose tissue dynamics, and the effects of vaccination [1] [2].
