Rapoehn, Inka and Elias, Ivet and Weiner, Juliane and Pujol, Anna and Kehr, Stephanie and Chadt, Alexandra and Al-Hasani, Hadi and Burkhardt, Ralph and Kloeting, Nora and Stumvoll, Michael and Bosch, Fatima and Kovacs, Peter and Heiker, John T. and Breitfeld, Jana (2023) Overexpressing high levels of human vaspin limits high fat diet-induced obesity and enhances energy expenditure in a transgenic mouse. FRONTIERS IN ENDOCRINOLOGY, 14: 1146454. ISSN 1664-2392,
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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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | VISCERAL ADIPOSE-TISSUE; HEPARIN-BINDING; SERUM VASPIN; KALLIKREIN 7; BETA-SHEET; INFLAMMATION; INSULIN; EXPRESSION; SERPINA12; INHIBITOR; serpin; metabolic disease; obesity; adipose tissue; mouse model; inflammation |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 30 Jan 2024 10:57 |
| Last Modified: | 30 Jan 2024 10:57 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60715 |
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