Back

Role of Hypertrophic Adipocytes, Collagen VI and CD38 in Fat Fibrosis of Patients with Obesity

Cinti, S.; Di Vincenzo, A.; Luca, T.; Perugini, J.; Lezoche, G.; Barresi, V.; De Geronimo, V.; Donati, A.; Casarotta, E.; Tomasello, M.; Pezzino, S.; Scuderi, C.; Di Cristoforo, A.; Pieroni, A.; Petrelli, M.; Napoli, M. V.; Figueiredo, N.; Campos Corgosinho, F.; Sbarbati, A.; Merlini, L.; Sabatelli, P.; Graciotti, L.; Spadoni, T.; DANI, C.; Mattioli Belmonte Cima, M.; Condorelli, D.; Gabrielli, A.; Malavasi, F.; Giordano, A.; Castorina, S.

2025-10-08 cell biology
10.1101/2025.10.08.681115 bioRxiv
Show abstract

Fat fibrosis correlates to metabolic consequences in patients with obesity, and is due to three types of collagen: I and III (fibrillar) and VI (non-fibrillar). In this sudy the extent of fibrosis in obese patients (n 50) was significant only in visceral parenchymal fat (4.7% vs 2.5% in controls (n 15) P<0.0001) and not in subcutaneous fat. Electron microscopy, in vivo and in vitro data, suggested that obese adipocytes are responsible for fibrillar collagen (I and III) production. COL6 (gene producing the non fibrillar form) resulted less expressed. In line, patients with COL6 mutations, showed increased fibrotic tissue even in subcutaneous fat: about 6.5 times vs controls in the patient with the severe form (Ullrich) and 2.8 times in two patients with the milder form (Bethlem). Approximately 15% of obese adipocytes were dead (perilipin1 negative), and consequent infiltrating macrophages showed hyperexpression of CD38, an ectoenzyme implicated in systemic fibrosis. Correlations with gene expression confirmed the importance also of myofibroblasts and the extracellular matrix peptidase D. All together our data support a role for obese adipocytes in the fibrillar collagen production and evidentiate collagen VI and CD38 as new molecular determinants, reinforcing the idea of a multi-factorial origin of fat fibrosis.

Matching journals

The top 13 journals account for 50% of the predicted probability mass.

50% of probability mass above

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.