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High dose of linagliptin induces thermogenic beige adipocytes in the subcutaneous white adipose tissue in diet-induced obese C57BL/6 mice.
- Source :
-
Endocrine [Endocrine] 2019 Aug; Vol. 65 (2), pp. 252-262. Date of Electronic Publication: 2019 Jun 03. - Publication Year :
- 2019
-
Abstract
- Purpose: To verify whether the treatment with linagliptin induces the browning of the subcutaneous WAT (sWAT) and thermogenesis in murine diet-induced obesity (DIO) model.<br />Methods: Forty animals were randomly assigned to receive a control diet (C, 10% lipids as energy) or a high-fat diet (HF, 50% lipids as energy) for 10 weeks. Each group was re-divided to begin the 5-week treatment, totalizing four experimental groups: C, C-L (C plus linagliptin, 30 mg/kg body mass; BM), HF, and HF-L (HF plus linagliptin, 30 mg/kg BM). The drug was mixed with diet.<br />Results: HF animals showed overweight, glucose intolerance, and a greater cross-sectional area of adipocytes. The treatment with linagliptin was able to normalize the BM, restore the glucose tolerance and the cross-sectional area of adipocytes. These observations comply with the observation of UCP1-positive multilocular adipocytes in the sWAT of treated animals. Both treated groups (C-L and HF-L) showed high expression of thermogenic and type 2 cytokines genes, which agree with the enhanced body temperature and the lower respiratory exchange ratio, implying enhanced thermogenesis with the use of lipids as fuel.<br />Conclusions: The reduced BM, the enhanced body temperature, and the presence of positive UCP1 beige cells in the sWAT point to the activation of the browning cascade on the sWAT of linagliptin-treated mice, and hence, linagliptin could induce the thermogenic pathway as a pleiotropic effect that can have translational potential.
- Subjects :
- Adipocytes, Brown
Adiposity
Animals
Biomarkers metabolism
Diet, High-Fat adverse effects
Dipeptidyl-Peptidase IV Inhibitors pharmacology
Disease Models, Animal
Insulin blood
Linagliptin pharmacology
Male
Mice, Inbred C57BL
Obesity blood
Obesity etiology
Random Allocation
Subcutaneous Fat cytology
Subcutaneous Fat metabolism
Dipeptidyl-Peptidase IV Inhibitors therapeutic use
Linagliptin therapeutic use
Obesity drug therapy
Subcutaneous Fat drug effects
Thermogenesis drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1559-0100
- Volume :
- 65
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Endocrine
- Publication Type :
- Academic Journal
- Accession number :
- 31161561
- Full Text :
- https://doi.org/10.1007/s12020-019-01969-y