4.5 Article

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

Journal

MOLECULAR BIOLOGY REPORTS
Volume 50, Issue 7, Pages 5755-5765

Publisher

SPRINGER
DOI: 10.1007/s11033-023-08460-y

Keywords

Obesity; Adipogenesis; Angiogenesis; ER stress; sXBP-1; PPAR gamma 2; WNT10B; HOMA-IR

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This study investigates the hypertrophy/hyperplasia of subcutaneous white adipose tissue (scWAT) in non-obese and different classes of obese individuals. The results reveal that Class I obese individuals exhibit inflammation, insulin resistance, and ER stress with hypertrophic scWAT adipocytes and limited adipose tissue expansion ability. In contrast, Class II + III obese individuals show adipogenesis through hyperplasia, indicating the involvement of PPAR?2 and CD31 levels. Therefore, therapeutic strategies that support both angiogenesis and adipogenesis can effectively prevent obesity complications.
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, PPAR?2, 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 TNFa, 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 PPAR?2 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.

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