Leptin and TGF-β1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes.

Bruno, Andreina; Di Sano, Caterina; Simon, Hans-Uwe; Chanez, Pascal; Patti, Angelo Maria; Di Vincenzo, Serena; Dino, Paola; D'Esposito, Vittoria; Formisano, Pietro; Beguinot, Francesco; Pace, Elisabetta (2021). Leptin and TGF-β1 Downregulate PREP1 Expression in Human Adipose-Derived Mesenchymal Stem Cells and Mature Adipocytes. Frontiers in cell and developmental biology, 9, p. 700481. Frontiers 10.3389/fcell.2021.700481

[img]
Preview
Text
Simon_leptin_and_TGF-B1.pdf - Published Version
Available under License Creative Commons: Attribution (CC-BY).

Download (3MB) | Preview

Adipose tissue is widely recognized as an extremely active endocrine organ producing adipokines as leptin that bridge metabolism and the immune system. Pre-B-cell leukemia homeobox (Pbx)-regulating protein-1 (PREP1) is a ubiquitous homeodomain transcription factor involved in the adipogenic differentiation and insulin-sensitivity processes. Leptin, as pleiotropic adipokine, and TGF-β, known to be expressed by primary pre-adipocytes [adipose-derived stem cells (ASCs)] and mature differentiated adipocytes, modulate inflammatory responses. We aimed to assess for the first time if leptin and TGF-β interfere with PREP1 expression in both ASCs and mature differentiated adipocytes. Human ASCs were isolated from subcutaneous adipose liposuction and, after expansion, fully differentiated to mature adipocytes. In both ASCs and adipocytes, leptin and TGF-β1 significantly decreased the expression of PREP1, alone and following concurrent Toll-like receptor 4 (TLR4) activation. Moreover, in adipocytes, but not in ASCs, leptin increased TLR4 and IL-33 expression, whereas TGF-β1 enhanced TLR4 and IL-6 expression. Taken together, we provide evidence for a direct regulation of PREP1 by leptin and TGF-β1 in ASCs and mature adipocytes. The effects of leptin and TGF-β1 on immune receptors and cytokines, however, are limited to mature adipocytes, suggesting that modulating immune responses depends on the differentiation of ASCs. Further studies are needed to fully understand the regulation of PREP1 expression and its potential for the development of new therapeutic approaches in obesity-related diseases.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Pharmacology

UniBE Contributor:

Simon, Hans-Uwe

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2296-634X

Publisher:

Frontiers

Language:

English

Submitter:

Celine Joray

Date Deposited:

08 Sep 2021 08:21

Last Modified:

12 Sep 2021 03:17

Publisher DOI:

10.3389/fcell.2021.700481

PubMed ID:

34327205

Uncontrolled Keywords:

PREP1 TGF-beta1 TLR4 adipocyte-derived stem cells adipocytes adipose tissue immune system leptin

BORIS DOI:

10.48350/158316

URI:

https://boris.unibe.ch/id/eprint/158316

Actions (login required)

Edit item Edit item
Provide Feedback