Age of obesity onset affects subcutaneous adipose tissue cellularity differently in the abdominal and femoral region.

OBJECTIVE: We aimed to examine the effect of age of obesity onset, sex, and their interaction on abdominal and femoral subcutaneous adipose tissue (SAT) morphology (degree of adipocyte hyperplasia or hypertrophy). METHODS: In this cross-sectional study, we isolated adipocytes via collagenase digestion from abdominal and femoral SAT biopsies taken from male and female adults with childhood-onset obesity (CO; n = 8 males, n = 16 females) or adult-onset obesity (AO; n = 8 males, n = 13 females). Regional body composition was measured with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan. Mean adipocyte size was measured in abdominal and femoral SAT and was used to quantify morphology in android and gynoid subcutaneous fat, respectively. RESULTS: Abdominal SAT morphology was more hyperplastic in females with CO than females with AO (p = 0.004) but did not differ between males with CO and males with AO (p = 0.996). Conversely, femoral SAT morphology was more hypertrophic in males and females with CO than those with AO. CONCLUSIONS: Age of obesity onset appears to affect SAT morphology differently in the abdominal and femoral regions of male and female adults. Our findings challenge the notion that SAT is uniformly hyperplastic in CO and hypertrophic in AO.

Association between rs174537 FADS1 polymorphism and immune cell profiles in abdominal and femoral subcutaneous adipose tissue: an exploratory study in adults with obesity.

Fatty acid desaturase 1 (FADS1) polymorphisms alter fatty acid content in subcutaneous adipose tissue (SAT); however, existing evidence is limited and conflicting regarding the association between FADS1 variants and SAT inflammatory status. To advance this area, we conducted an exploratory study to investigate whether the common rs174537 polymorphism in FADS1 was associated with immune cell profiles in abdominal and femoral SAT in individuals with obesity. FADS1 gene expression and immune cell profiles in SAT depots were assessed by qPCR and flow cytometry, respectively. Although FADS1 gene expression was associated with genotype, no associations were observed with immune cell profiles in either depot. Our study provides additional evidence that rs174537 in FADS1 has minimal impact on inflammatory status in obese SAT.

Sex Affects Regional Variations in Subcutaneous Adipose Tissue T Cells but not Macrophages in Adults with Obesity.

OBJECTIVE: The inflammatory environment in lower-body subcutaneous adipose tissue (SAT) has been largely unexplored. This study aimed to examine the effects of region (upper body vs. lower body) and sex on SAT immune cell profiles in young adults with obesity. METHODS: Abdominal (AB) and femoral (FEM) SAT was collected from 12 males (mean [SEM] age = 30.8 [1.4] years; mean [SEM] BMI = 34.1 [1.1] kg/m2 ) and 22 females (mean [SEM] age = 30.6 [0.6] years; mean [SEM] BMI = 34.0 [0.7] kg/m2 ) with obesity via needle aspiration. Flow cytometry was used to quantify macrophage (CD68+) and T-cell (CD3+) subpopulations in the stromovascular fraction of each SAT region. RESULTS: Females had a greater proportion of most T-cell types (CD3+CD4+CD45RA+, CD3+CD4+CD45RA-, and CD3+CD8+CD45RA+) in FEM compared with AB SAT, while males had similar proportions in both regions. Regardless of sex, the M1-like macrophage population (CD68+CD206-) was proportionally higher in AB SAT than in FEM SAT. CONCLUSIONS: Results showed that T-cell populations vary by SAT region in females but not males. Both sexes, however, have proportionately more proinflammatory macrophages in upper-body than in lower-body SAT. It remains to be seen how these unique immune cell profiles in males and females with obesity contribute to adipose tissue inflammation and metabolic disease risk.

Acetyl-CoA Regulation, OXPHOS Integrity and Leptin Levels Are Different in Females With Childhood vs Adulthood Onset of Obesity.

Although childhood-onset obesity (CO) and adulthood-onset obesity (AO) are known to lead to distinctive clinical manifestations and disease risks, the fundamental differences between them are largely unclear. The aim of the current study is to investigate the fundamental differences between subcutaneous adipose tissue from CO and AO and to identify metabolic differences between abdominal (abSAT) and femoral subcutaneous adipose tissues (feSAT). Total and regional body composition was assessed using dual-energy x-ray absorptiometry (DXA) and computed tomography. Levels of acetyl-CoA, NAD+/NADH, acetyl-CoA network genes, mitochondrial complex abundance, H3 acetylation were determined in biopsied abSAT and feSAT. Serum leptin and adiponectin were measured. Our results showed that acetyl-CoA was higher in subcutaneous adipose tissue from subjects with AO compared with CO. Multiple linear regression revealed that ATP citrate lyase was the only main effect affecting the level of acetyl-CoA. Circulating leptin concentrations was higher in AO. The increased level of acetyl-CoA was strongly associated with histone H3 acetylation, LEP expression in adipose tissue, and circulating leptin in AO. NAD+/NADH was higher in CO; however, abundance of mitochondrial complexes, the complex II:complex V ratio, and the complex IV:complex V ratio were lower in CO, reflecting compromised mitochondrial function in subcutaneous adipose tissue from CO. Moreover, we identified differences in the level of acetyl-CoA and NAD+/NADH ratio between abSAT and feSAT, suggesting that these fat depots may possess different metabolic properties. The fundamental difference in the important metabolic intermediate acetyl-CoA between CO and AO may help us better understand the development of obesity and the pathogenesis of different obesity-related diseases in humans.