2/29/2024 0 Comments Apple body shapeParticipants were excluded if they reported a history of chronic disease (diabetes, heart or liver disease, high blood pressure, gastrointestinal disorder), recent weight loss or gain (> 3 kg over the past 12 weeks), had abnormal blood or urine values, or use of oral contraceptives or hormone replacement therapy. Twenty-one healthy, eumenorrheic, premenopausal, weight-stable women age 20 to 40 years with a body mass index (BMI) between 24.8 and 33.9 kg/m 2 were recruited in Orlando, Florida, using advertisements approved by an institutional review board. Clinical Study Design and Participant Details Our studies reported here suggest that specific subcutaneous fat cells, identifiable by gene expression and chromatin openness, are part of distinct fat distribution and may account for early signs of MetS observed in otherwise healthy, apple-shaped, premenopausal women.Ī. By using a combination of clinical assessments, RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin using sequencing (ATAC-seq) technologies coupled with a comprehensive bioinformatic analysis, we unraveled the unique transcriptional signatures and open chromatin profiles of ABD- and GF-adipocyte fraction in apple- and pear-shaped women. To test this hypothesis, we isolated the adipocyte fraction from abdominal and GF scWAT biopsies obtained from groups of “apple” vs “pear” women segregated initially only by their waist-to-hip ratio (WHR) value. We hypothesized that differential chromatin openness plays an early role in AT deposition, before any appearance of metabolic complications, partially by regulating expression of body-shape–specific genes in the scWAT depots. Still unexplored, however, are the molecular features and epigenetic signatures within the abdominal and GF-derived adipocyte that might differ between women with an “apple” vs “pear” body shape. In addition, there are distinct gene expression signatures and differential CpG island methylation and histone marks in abdominal vs GF scWAT, suggesting that there is an epigenomic code that underlies the known functional differences in scWAT depots. Previous publications highlighted the differential tissue and cellular phenotypes existing between adipocytes isolated from subcutaneous ABD fat relative to lower-body fat depots for example, adipocyte size, basal lipolysis, dietary fatty acid uptake, and insulin suppression of lipolysis vary according to the depot-specific origin of the fat analyzed. These correlation data suggest that an impaired GF fat expansion could be a significant determinant of diabetes and cardiovascular diseases. A recent integrative genomic analysis revealed 53 genomic loci strongly associated with IR, T2D, and coronary heart disease that were also related to lower hip circumference and reduced levels of gynoid and leg fat mass. In contrast, individuals with lower-body obesity, characterized by preferential fat accumulation in the subcutaneous gluteofemoral (GF) depot and referred as a “pear-shaped” body, are at a lower risk for developing MetS. The subcutaneous abdominal (ABD) fat is positively associated with risk factors of obesity-related complications and has been implicated in the prevalence of MetS independently from the visceral fat mass. In contrast, the subcutaneous white adipose tissue (scWAT) is the largest fat depot in humans. However, this depot accounts for only 2% to 3% of the total body fat in women and contributes to no more than 15% of the total systemic FFA. ![]() According to this hypothesis, the visceral depot, which drains directly to the liver, plays a significant role and has been the focus of many studies. Moreover, elevated FFA levels also inhibit insulin’s antilipolytic action on adipose tissue (AT), which will further increase the rate of FFA release into the circulation, resulting in a vicious cycle. As a result, there is an ectopic accumulation of lipids in other major insulin target tissues (skeletal muscle, liver, and endothelial cells) that leads to global insulin resistance (IR) and systemic inflammation. A major contributing factor is thought to be the presence of dysfunctional adipocytes, characterized by excess release of free fatty acids (FFAs) and inflammatory molecules. Central obesity, defined by an elevated waist circumference and often denoted as an “apple-shaped” body, is believed to be at the core of the syndrome. ![]() Metabolic syndrome (MetS) is associated with a collection of several clinical phenotypes and is linked with increased risk of multiple chronic diseases, including type 2 diabetes (T2D), cancer, and cardiovascular disease.
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