Overexpressing high levels of human vaspin limits high fat diet-induced obesity and enhances energy expenditure in a transgenic mouse
Rapöhn, Inka (University of Leipzig)
Elias Puigdomenech, Ivet (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Weiner, Juliane (University of Leipzig Medical Center)
Pujol, Anna (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Kehr, Stephanie (Leipzig University)
Chadt, Alexandra (German Center for Diabetes Research)
Al-Hasani, Hadi (German Center for Diabetes Research)
Burkhardt, Ralph (University Hospital Regensburg)
Klöting, Nora (University of Leipzig)
Stumvoll, Michael (University of Leipzig)
Bosch i Tubert, Fàtima (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Kovacs, Peter (German Center for Diabetes Research)
Heiker, John T. (University of Leipzig Medical Center)
Breitfeld, Jana (Leipzig Medical Center)

Data:	2023
Resum:	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.
Drets:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Llengua:	Anglès
Document:	Article ; recerca ; Versió publicada
Matèria:	Serpin ; Metabolic disease ; Obesity ; Adipose tissue ; Mouse model ; Inflammation
Publicat a:	Frontiers in endocrinology, Vol. 14 (April 2023) , art. 1146454, ISSN 1664-2392

DOI: 10.3389/fendo.2023.1146454
PMID: 37152954

9 p, 8.0 MB

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