Differences in subcutaneous abdominal adipose tissue (SAT) fat cell size and number (cellularity) are linked to insulin resistance. Men are generally more insulin resistant than women but it is unknown whether there is a gender dimorphism in SAT cellularity. The objective was to determine SAT cellularity and its relationship to insulin sensitivity in men and women.
In a cohort study performed at an outpatient academic clinic in Sweden, 798 women and 306 men were included. Estimated SAT mass (ESAT) was derived from measures of dual-energy X-ray absorptiometry and a formula. SAT biopsies were obtained to measure mean fat cell size; SAT adipocyte number was obtained by dividing ESAT with mean fat cell weight. Fat cell size was also compared with level of insulin sensitivity in vivo.
Over the entire range of body mass index (BMI) both fat cell size and number correlated positively with ESAT in either sex. On average, fat cell size was larger in men than in women, which was driven by significantly larger fat cells in non-obese men compared with non-obese women; no gender effect on fat cell size was seen in obese subjects. For all subjects fat cell number was larger in women than men, which was driven by a gender effect among non-obese individuals (P
Cross-sectional studies show that white adipose tissue hypertrophy (few, large adipocytes), in contrast to hyperplasia (many, small adipocytes), associates with insulin resistance and increased risk of developing type 2 diabetes. We investigated if baseline adipose cellularity could predict improvements in insulin sensitivity following weight loss.
Plasma samples and subcutaneous abdominal adipose biopsies were examined in 100 overweight or obese individuals before and 10 weeks after a hypocaloric diet (7±3% weight loss) and in 61 obese subjects before and 2 years after gastric by-pass surgery (33±9% weight loss). The degree of adipose tissue hypertrophy or hyperplasia (termed the morphology value) in each individual was calculated on the basis of the relationship between fat cell volume and total fat mass. Insulin sensitivity was determined by homeostasis model assessment-estimated insulin resistance (HOMAIR).
In both cohorts at baseline, subjects with hypertrophy displayed significantly higher fasting plasma insulin and HOMAIR values than subjects with hyperplasia (P
Obese subjects have increased number of enlarged fat cells that are reduced in size but not in number in post-obesity. We performed DNA methylation profiling in fat cells with the aim of identifying differentially methylated DNA sites (DMS) linked to adipose hyperplasia (many small fat cells) in post-obesity.
Genome-wide DNA methylation was analyzed in abdominal subcutaneous fat cells from 16 women examined 2 years after gastric bypass surgery at a post-obese state (body mass index (BMI) 26±2?kg?m(-2), mean±s.d.) and from 14 never-obese women (BMI 25±2?kg?m(-2)). Gene expression was analyzed in subcutaneous adipose tissue from nine women in each group. In a secondary analysis, we examined DNA methylation and expression of adipogenesis genes in 15 and 11 obese women, respectively.
The average degree of DNA methylation of all analyzed CpG sites was lower in fat cells from post-obese as compared with never-obese women (P=0.014). A total of 8504 CpG sites were differentially methylated in fat cells from post-obese versus never-obese women (false discovery rate 1%). DMS were under-represented in CpG islands and surrounding shores. The 8504 DMS mapped to 3717 unique genes; these genes were over-represented in cell differentiation pathways. Notably, 27% of the genes linked to adipogenesis (that is, 35 of 130) displayed DMS (adjusted P=10(-8)) in post-obese versus never-obese women. Next, we explored DNA methylation and expression of genes linked to adipogenesis in more detail in adipose tissue samples. DMS annotated to adipogenesis genes were not accompanied by differential gene expression in post-obese compared with never-obese women. In contrast, adipogenesis genes displayed differential DNA methylation accompanied by altered expression in obese women.
Global CpG hypomethylation and over-representation of DMS in adipogenesis genes in fat cells may contribute to adipose hyperplasia in post-obese women.
Visceral fat accumulation relates to cardiovascular risk factors, but the underlying mechanisms are not well understood. We investigated the role of visceral adipocyte triglyceride breakdown (lipolysis) for several risk factors of cardiovascular disease. In 73 obese women, fat mass and distribution, blood pressure, blood samples for cardiometabolic risk factors, and whole-body insulin sensitivity were determined. A subcutaneous and a visceral fat biopsy were taken. Fat cell glycerol release after stimulation with a major lipolytic hormone, noradrenaline, was measured. In simple regression analysis, visceral fat cell lipolysis, but not subcutaneous adipocyte lipolysis was related to components of the metabolic syndrome. Moreover, subjects in the highest quartile of catecholamine-induced visceral lipolysis had higher levels of systolic blood pressure, estimated liver fat, plasma levels of glucose, insulin, cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B and lower whole-body insulin sensitivity than those in the lowest quartile (p=0.0004-0.048). Among subjects with the metabolic syndrome, visceral fat cell lipolysis was 40% higher than in the remaining subjects (p=0.0052). Catecholamine-activated lipolysis in visceral but not subcutaneous fat cells is associated with cardiovascular risk factors in obesity.