Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat Diet
ABSTRACT Background Sodium glucose‐linked transporter 2 (SGLT2) inhibitors promote glucose, and therefore calorie, excretion in the urine. Patients taking SGLT2 inhibitors typically experience mild weight loss, but the amount of weight loss falls short of what is expected based on caloric loss. Unde...
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| Format: | Article |
| Language: | English |
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Wiley
2024-03-01
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| Series: | Endocrinology, Diabetes & Metabolism |
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| Online Access: | https://doi.org/10.1002/edm2.475 |
| _version_ | 1797246684030304256 |
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| author | Anh T. Nguyen Zachary Amigo Kathleen McDuffie Victoria C. MacQueen Lane D. Bell Lan K. Truong Gloria Batchi Sara M. McMillin |
| author_facet | Anh T. Nguyen Zachary Amigo Kathleen McDuffie Victoria C. MacQueen Lane D. Bell Lan K. Truong Gloria Batchi Sara M. McMillin |
| author_sort | Anh T. Nguyen |
| collection | DOAJ |
| description | ABSTRACT Background Sodium glucose‐linked transporter 2 (SGLT2) inhibitors promote glucose, and therefore calorie, excretion in the urine. Patients taking SGLT2 inhibitors typically experience mild weight loss, but the amount of weight loss falls short of what is expected based on caloric loss. Understanding the mechanisms responsible for this weight loss discrepancy is imperative, as strategies to improve weight loss could markedly improve type 2 diabetes management and overall metabolic health. Methods Two mouse models of diet‐induced obesity were administered the SGLT2 inhibitor empagliflozin in the food for 3 months. Urine glucose excretion, body weight, food intake and activity levels were monitored. In addition, serum hormone measurements were taken, and gene expression analyses were conducted. Results In both mouse models, mice receiving empagliflozin gained the same amount of body weight as their diet‐matched controls despite marked glucose loss in the urine. No changes in food intake, serum ghrelin concentrations or activity levels were observed, but serum levels of fibroblast growth factor 21 (FGF21) decreased after treatment. A decrease in the levels of deiodinase 2 (Dio2) was also observed in the white adipose tissue, a primary target tissue of FGF21. Conclusion These findings suggest that compensatory metabolic adaptations, other than increased food intake or decreased physical activity, occur in response to SGLT2 inhibitor‐induced glycosuria that combats weight loss, and that reductions in FGF21, along with subsequent reductions in peripheral Dio2, may play a role. |
| first_indexed | 2024-04-24T19:46:42Z |
| format | Article |
| id | doaj.art-ccb11baa871045f0b709f966c9954579 |
| institution | Directory Open Access Journal |
| issn | 2398-9238 |
| language | English |
| last_indexed | 2024-04-24T19:46:42Z |
| publishDate | 2024-03-01 |
| publisher | Wiley |
| record_format | Article |
| series | Endocrinology, Diabetes & Metabolism |
| spelling | doaj.art-ccb11baa871045f0b709f966c99545792024-03-25T06:14:31ZengWileyEndocrinology, Diabetes & Metabolism2398-92382024-03-0172n/an/a10.1002/edm2.475Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat DietAnh T. Nguyen0Zachary Amigo1Kathleen McDuffie2Victoria C. MacQueen3Lane D. Bell4Lan K. Truong5Gloria Batchi6Sara M. McMillin7Fred Wilson School of Pharmacy High Point University High Point North Carolina USAFred Wilson School of Pharmacy High Point University High Point North Carolina USAFred Wilson School of Pharmacy High Point University High Point North Carolina USAFred Wilson School of Pharmacy High Point University High Point North Carolina USAFred Wilson School of Pharmacy High Point University High Point North Carolina USAFred Wilson School of Pharmacy High Point University High Point North Carolina USAFred Wilson School of Pharmacy High Point University High Point North Carolina USAFred Wilson School of Pharmacy High Point University High Point North Carolina USAABSTRACT Background Sodium glucose‐linked transporter 2 (SGLT2) inhibitors promote glucose, and therefore calorie, excretion in the urine. Patients taking SGLT2 inhibitors typically experience mild weight loss, but the amount of weight loss falls short of what is expected based on caloric loss. Understanding the mechanisms responsible for this weight loss discrepancy is imperative, as strategies to improve weight loss could markedly improve type 2 diabetes management and overall metabolic health. Methods Two mouse models of diet‐induced obesity were administered the SGLT2 inhibitor empagliflozin in the food for 3 months. Urine glucose excretion, body weight, food intake and activity levels were monitored. In addition, serum hormone measurements were taken, and gene expression analyses were conducted. Results In both mouse models, mice receiving empagliflozin gained the same amount of body weight as their diet‐matched controls despite marked glucose loss in the urine. No changes in food intake, serum ghrelin concentrations or activity levels were observed, but serum levels of fibroblast growth factor 21 (FGF21) decreased after treatment. A decrease in the levels of deiodinase 2 (Dio2) was also observed in the white adipose tissue, a primary target tissue of FGF21. Conclusion These findings suggest that compensatory metabolic adaptations, other than increased food intake or decreased physical activity, occur in response to SGLT2 inhibitor‐induced glycosuria that combats weight loss, and that reductions in FGF21, along with subsequent reductions in peripheral Dio2, may play a role.https://doi.org/10.1002/edm2.475diabetesFGF21metabolismSGLT2 inhibitor |
| spellingShingle | Anh T. Nguyen Zachary Amigo Kathleen McDuffie Victoria C. MacQueen Lane D. Bell Lan K. Truong Gloria Batchi Sara M. McMillin Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat Diet Endocrinology, Diabetes & Metabolism diabetes FGF21 metabolism SGLT2 inhibitor |
| title | Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat Diet |
| title_full | Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat Diet |
| title_fullStr | Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat Diet |
| title_full_unstemmed | Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat Diet |
| title_short | Effects of Empagliflozin‐Induced Glycosuria on Weight Gain, Food Intake and Metabolic Indicators in Mice Fed a High‐Fat Diet |
| title_sort | effects of empagliflozin induced glycosuria on weight gain food intake and metabolic indicators in mice fed a high fat diet |
| topic | diabetes FGF21 metabolism SGLT2 inhibitor |
| url | https://doi.org/10.1002/edm2.475 |
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