1. Anti-adipogenic signals at the onset of obesity-related inflammation in white adipose tissue.
- Author
-
Caputo T, Tran VDT, Bararpour N, Winkler C, Aguileta G, Trang KB, Giordano Attianese GMP, Wilson A, Thomas A, Pagni M, Guex N, Desvergne B, and Gilardi F
- Subjects
- Adipose Tissue, White cytology, Adipose Tissue, White pathology, Animals, Diet, High-Fat, Fatty Acid-Binding Proteins genetics, Fatty Acid-Binding Proteins metabolism, Gene Expression Regulation, Inflammation etiology, Inflammation metabolism, Interleukin-1beta genetics, Interleukin-1beta metabolism, Intra-Abdominal Fat cytology, Intra-Abdominal Fat metabolism, Intra-Abdominal Fat pathology, Lipid Metabolism, Male, Mice, Mice, Inbred C57BL, Obesity complications, Signal Transduction genetics, Stem Cells cytology, Stem Cells metabolism, Subcutaneous Fat cytology, Subcutaneous Fat metabolism, Subcutaneous Fat pathology, Tumor Necrosis Factor-alpha genetics, Tumor Necrosis Factor-alpha metabolism, Wnt Proteins metabolism, Adipogenesis, Adipose Tissue, White metabolism, Cell Differentiation, Inflammation pathology, Obesity pathology
- Abstract
Chronic inflammation that affects primarily metabolic organs, such as white adipose tissue (WAT), is considered as a major cause of human obesity-associated co-morbidities. However, the molecular mechanisms initiating this inflammation in WAT are poorly understood. By combining transcriptomics, ChIP-seq and modeling approaches, we studied the global early and late responses to a high-fat diet (HFD) in visceral (vWAT) and subcutaneous (scWAT) AT, the first being more prone to obesity-induced inflammation. HFD rapidly triggers proliferation of adipocyte precursors within vWAT. However, concomitant antiadipogenic signals limit vWAT hyperplastic expansion by interfering with the differentiation of proliferating adipocyte precursors. Conversely, in scWAT, residing beige adipocytes lose their oxidizing properties and allow storage of excessive fatty acids. This phase is followed by tissue hyperplastic growth and increased angiogenic signals, which further enable scWAT expansion without generating inflammation. Our data indicate that scWAT and vWAT differential ability to modulate adipocyte number and differentiation in response to obesogenic stimuli has a crucial impact on the different susceptibility to obesity-related inflammation of these adipose tissue depots.
- Published
- 2021
- Full Text
- View/download PDF