Obesity is a major public health problem and a risk factor for type-2 diabetes, hypertension and cardiovascular disease [1-4]. Adipose tissue is an endocrine organ [5] and plays a fundamental role in obesity-related metabolic dysfunction [6]. Different adipose tissue depots within the body have distinct structural and biochemical properties [7,8]. In humans, these depots can broadly be divided into two categories, subcutaneous and intra-abdominal. Metabolic risk is affected by both the distribution of body fat between different adipose tissue depots within an individual and the differing natures of the depots themselves [9-11]. Increased intra-abdominal adipose tissue has been correlated with an increased risk of obesity-related co-morbidities such as cardiovascular disease, atherosclerosis and type-2 diabetes [12-14].
- Outcome of bone-patellar tendon-bone vs hamstring tendon autograft for anterior cruciate ligament reconstruction: A meta-analysis of randomized controlled trials with a 5-year minimum follow-up
- Mini Skillet Bowl from Taco Bell: Allergens, Calories, Fats
- How Long Does an Eye Exam Take?
- “Fear is only as deep as the mind allows”
- Barium chlorite hydrate, Ba(ClO2 )2 ·3.5H2 O
Causal genetic variants of obesity and type-2 diabetes have been identified through candidate gene, family-based linkage and large scale association analyses. However, apart from the small number of rare monogenic disease variants application of genetics to clinical management has not occurred. Reasons for this include the relatively small effect size of common genetic variants, the location of a large number of disease associated loci in intergenic regions of the genome, and the likelihood that additional causal variants are yet to be identified [15,16].
Xem thêm : Gifts That Give Back
It is now recognised that epigenetics plays a significant role in complex disease, and provides mechanisms whereby environmental factors can influence complex diseases such as obesity and type-2 diabetes [17,18]. Thus, epigenetics may explain some of the ‘missing heritability’ of complex disease, and, because of effects on regulation, provide a functional role for some of the intergenic loci associated with disease.
Animal and human studies have shown that the DNA methylation status of genes in offspring can be altered in utero by the maternal dietary environment [19-23]. Godfrey et al. [24] further reported that the child’s methylation status correlated with adiposity in later life. Feinberg et al. [25] identified four variably methylated regions in lymphocytes which correlated with body mass index (BMI); these regions were located in or near genes previously implicated in body weight regulation or diabetes. Obesity has also been associated with genome-wide DNA methylation changes in peripheral blood [26-28], and methylation differences have been reported in peripheral blood in response to caloric restriction [29] and weight loss intervention [30]. In addition, a recent genome-wide analysis of peripheral blood revealed type-2 diabetes related DNA methylation variations [31], and another investigated associations between methylation and fasting glucose, insulin and insulin resistance [32].
Xem thêm : Grilled Lamb Chops Recipe with Bonus Guide to Cuts
Epigenetic signatures are acquired by cells during development and differentiation. DNA methylation changes, such as demethylation of specific sequences within the leptin and GLUT4 gene promoters is observed during adipogenesis [33,34] and adipose tissue precursor cells retain their DNA methylation profile through generations of culture [35]. In addition, women with a lower baseline methylation of the leptin and TNF-alpha gene promoters in subcutaneous adipose tissue responded better to dietary intervention [36].
A small number of studies have reported DNA methylation profiling of human subcutaneous adipose tissue. The first, by Bouchard et al. [37] assayed 15 K CpG dinucleotides (CpGs) in subcutaneous adipose tissue from high (3% to 6% loss of body fat) and low (≤3% loss of body fat) responders to caloric restriction reporting DNA methylation differences between the two groups at 35 loci before weight loss and 3 loci after weight loss. More recently a couple of studies have investigated DNA methylation differences between twins [38,39] and another compared thigh subcutaneous adipose before and after exercise intervention [40]. Investigation of the omentum DNA methylome has been reported in the context of both an identification of tissue-specific differentially methylation using the Illumina 450 K platform [41], and a comparison of global methylation patterns with subcutaneous adipose using a luminometric assay [42].
Given this increasing evidence for the involvement of epigenetics in complex disease and obesity in particular [17,18], together with the role that adipose tissue plays in disease progression, we hypothesised that epigenetic changes would be present in this tissue in the context of obesity and weight loss. Roux en Y gastric bypass surgery (from now on referred to as gastric bypass) is used to treat morbid obesity and results in marked weight loss [43,44]. Therefore, we use gastric bypass as a model for significant weight loss. Two studies have investigated global DNA methylation before and after gastric bypass, one in skeletal muscle and the other in liver [45,46]. Here we extend this to two adipose tissue depots and present the first high density DNA methylation profile of subcutaneous abdominal and intra-abdominal omental adipose tissue before and after gastric bypass and weight loss.
Nguồn: https://buycookiesonline.eu
Danh mục: Info
