| Title: |
Loss of VSTM2A promotes adipocyte hypertrophy and disrupts metabolic homeostasis |
| Authors: |
Al Dow, Manal; Secco, Blandine; Mouchiroud, Mathilde; Rochette, Marianne; Gilio, Gustavo R.; Massicard, Mickael; Hardy, Marilou; Gélinas, Yves; Festuccia, William T.; Morissette, Mathieu C.; Manem, Venkata S. K.; Laplante, Mathieu |
| Contributors: |
Canadian Institutes of Health Research; Fonds de Recherche du Québec - Santé |
| Source: |
Obesity ; volume 33, issue 3, page 522-536 ; ISSN 1930-7381 1930-739X |
| Publisher Information: |
Wiley |
| Publication Year: |
2025 |
| Collection: |
Wiley Online Library (Open Access Articles via Crossref) |
| Description: |
Objective Adipose tissue expands through hyperplasia and hypertrophy to store excess lipids, a process that is essential for the maintenance of metabolic homeostasis. The mechanisms regulating adipocyte recruitment from progenitors remain unclear. We have previously identified V‐set and transmembrane domain‐containing protein 2A (VSTM2A) as a factor promoting fat cell development in vitro. Whether VSTM2A impacts adipose tissue and systemic metabolism in vivo is still unknown. Methods We generated VSTM2A knockout mice ( Vstm2a −/− ) using clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR‐associated protein 9 (Cas9) and fed them either a chow or high‐fat diet. These mice were evaluated for body weight, adiposity, blood parameters, and glucose homeostasis. Results Vstm2a −/− mice were viable and showed no body weight differences. Although adipose mass was similar, Vstm2a −/− mice had larger adipocytes, an effect linked to inflammation, ectopic lipid deposition, and impaired glucose and lipid metabolism. Transcriptomic analysis revealed that VSTM2A loss affects the expression of several genes in adipose tissue, including some related to the lysosome. Interestingly, acute lysosomal inhibition early in life is sufficient to cause adipocyte hypertrophy in adults. Conclusions VSTM2A is dispensable for adipose tissue formation, but its loss causes adipocyte hypertrophy and impairs glucose and lipid homeostasis. Our study also underscores a critical role of the lysosome in initiating adipogenesis. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1002/oby.24224 |
| Availability: |
https://doi.org/10.1002/oby.24224; https://onlinelibrary.wiley.com/doi/pdf/10.1002/oby.24224 |
| Rights: |
http://creativecommons.org/licenses/by-nc/4.0/ |
| Accession Number: |
edsbas.7986A0A2 |
| Database: |
BASE |