The size of human subcutaneous adipocytes, but not adiposity, is associated with inflammation, endoplasmic reticulum stress, and insulin resistance markers

Abstract

Background The fat storage capacity of the adipose tissue prevents ectopic lipid deposition, which is one of the risk factors for metabolic abnormalities in obesity. This capacity depends upon the adipogenic gene expression and blood supply provision for tissue expansion through angiogenesis. Here, we studied hyperplasia/hypertrophy of subcutaneous white adipose tissue (scWAT) concerning adipogenic gene expression, angiogenic status, and metabolic parameters in non-obese and different classes of obese individuals. Methods The scWAT samples were collected from 80 individuals. The anthropometric parameters, adipose tissue cell size, serum biochemistry, ER stress-induced XBP1 splicing, PPARγ2, SFRP1, WNT10B, and VEGFA gene expression levels were studied. In addition, the CD31 level was investigated by Western blotting. Results The obese individuals had greater waist circumferences and higher serum TG, TC, insulin, and HOMA-IR than the non-obese group. However, the largest adipocyte size, increased TNFα, insulin, and HOMA-IR, and the highest expression level of sXBP1, WNT10B, and VEGFA were observed in Class I obese individuals. It means that inflammation, insulin resistance, and ER stress accompany hypertrophic scWAT adipocytes with limited adipose tissue expansion ability. Furthermore, the Class II + III obese individuals showed high PPARγ2 expression and CD31 levels. There is adipogenesis through hyperplasia in this group. The SFRP1 expression was not significantly different in the studied groups. Conclusion The results suggest that the capability of adipogenesis with inadequate angiogenesis is related to the metabolic status, inflammation, and ER function. Therefore, therapeutic strategies that support both angiogenesis and adipogenesis can effectively prevent the complications of obesity.

Single-nucleus RNA-sequencing reveals NRF1/NFE2L1 as a key factor determining the thermogenesis and cellular heterogeneity and dynamics of brown adipose tissues in mice

“…It has been well documented that hypertrophic adipocytes are prone to developing organelle dysfunction, such as ER stress, mitochondrial dysfunction, and activation of the NLRP3 inflammasome pathway [ 42 , 43 ], suggesting that hypertrophically stressed adipocytes undergo pyroptotic cell death and initiate an inflammatory response. Given that BAC in Nfe2l1 (f)-KO mice exhibit noticeable hypertrophy, we reason that the BAT inflammation is the secondary consequence of hypertrophic stress.…”