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Rapöhn, I. ; Elias, I.* ; Weiner, J.* ; Pujol, A.* ; Kehr, S.* ; Chadt, A.* ; Al-Hasani, H.* ; Burkhardt, R.* ; Klöting, N. ; Stumvoll, M. ; Bosch, F.* ; Kovacs, P.* ; Heiker, J.T. ; Breitfeld, J.*

Overexpressing high levels of human vaspin limits high fat diet-induced obesity and enhances energy expenditure in a transgenic mouse.

Front. Endocrin. 14:1146454 (2023)

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Adipose tissue inflammation and insulin resistance are hallmarks in the development of metabolic diseases resulting from overweight and obesity, such as type 2 diabetes and non-alcoholic fatty liver disease. In obesity, adipocytes predominantly secrete proinflammatory adipokines that further promote adipose tissue dysfunction with negative effects on local and systemic insulin sensitivity. Expression of the serpin vaspin (SERPINA12) is also increased in obesity and type 2 diabetes, but exhibits compensatory roles in inflammation and insulin resistance. This has in part been demonstrated using vaspin-transgenic mice. We here report a new mouse line (h-vaspinTG) with transgenic expression of human vaspin in adipose tissue that reaches vaspin concentrations three orders of magnitude higher than wild type controls (>200 ng/ml). Phenotyping under chow and high-fat diet conditions included glucose-tolerance tests, measurements of energy expenditure and circulating parameters, adipose tissue and liver histology. Also, ex vivo glucose uptake in isolated adipocytes and skeletal muscle was analyzed in h-vaspinTG and littermate controls. The results confirmed previous findings, revealing a strong reduction in diet-induced weight gain, fat mass, hyperinsulinemia, -glycemia and -cholesterolemia as well as fatty liver. Insulin sensitivity in adipose tissue and muscle was not altered. The h-vaspinTG mice showed increased energy expenditure under high fat diet conditions, that may explain reduced weight gain and overall metabolic improvements. In conclusion, this novel human vaspin-transgenic mouse line will be a valuable research tool to delineate whole-body, tissue- and cell-specific effects of vaspin in health and disease.

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Publication type Article: Journal article

Document type Scientific Article

Corresponding Author

Keywords Adipose Tissue ; Inflammation ; Metabolic Disease ; Mouse Model ; Obesity ; Serpin; Visceral Adipose-tissue; Heparin-binding; Serum Vaspin; Kallikrein 7; Beta-sheet; Inflammation; Insulin; Expression; Serpina12; Inhibitor

ISSN (print) / ISBN 1664-2392

e-ISSN 1664-2392

Journal Frontiers in Endocrinology

Quellenangaben Volume: 14, Article Number: 1146454

Publisher Frontiers

Publishing Place Lausanne

Non-patent literature Publications

Reviewing status Peer reviewed

Institute(s) Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)