Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis
<p><strong>Objective:</strong> Metformin is a first-line pharmacotherapy in the treatment of type 2 diabetes, a condition closely associated with NAFLD. Although metformin promotes weight loss and improves insulin sensitivity, its effect on intrahepatic triglyceride (IHTG) remains...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
| Published: |
Bioscientifica
2022
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| _version_ | 1797106619317747712 |
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| author | Green, CJ Marjot, T Walsby-Tickle, J Charlton, C Cornfield, T Westcott, F Pinnick, KE Moolla, A Hazlehurst, JM McCullagh, J Tomlinson, JW Hodson, L |
| author_facet | Green, CJ Marjot, T Walsby-Tickle, J Charlton, C Cornfield, T Westcott, F Pinnick, KE Moolla, A Hazlehurst, JM McCullagh, J Tomlinson, JW Hodson, L |
| author_sort | Green, CJ |
| collection | OXFORD |
| description | <p><strong>Objective:</strong> Metformin is a first-line pharmacotherapy in the treatment of type 2 diabetes, a condition closely associated with NAFLD. Although metformin promotes weight loss and improves insulin sensitivity, its effect on intrahepatic triglyceride (IHTG) remains unclear.
We investigated the effect of metformin on IHTG, hepatic de novo lipogenesis (DNL) and
fatty acid (FA) oxidation in vivo in humans.</p>
<p><strong>Design and Methods:</strong> Metabolic investigations, using stable-isotope tracers, were performed in 10 insulin-resistant, overweight/obese human participants with NAFLD who were treatment naïve before and after 12-weeks of metformin treatment. The effect of metformin on markers of subcutaneous adipose tissue FA metabolism and function, along with the plasma metabolome were investigated.</p>
<p><strong>Results:</strong> Twelve weeks treatment with metformin resulted in a significant reduction in body weight and improved insulin sensitivity, but IHTG content and FA oxidation remained unchanged. Metformin treatment was associated with a significant decrease in VLDLtriglyceride (TG) concentrations and a significant increase in the relative contribution of
DNL-derived FAs to VLDL-TG. There were subtle and relatively few changes in subcutaneous adipose tissue FA metabolism and the plasma metabolome with metformin treatment.</p>
<p><strong>Conclusions:</strong> We demonstrate the mechanisms of action of metformin whereby it improves insulin sensitivity and promotes weight loss, without improvement in IHTG; these observations are partly, explained through increased hepatic DNL and a lack of change in
fatty acid oxidation.</p> |
| first_indexed | 2024-03-07T07:03:33Z |
| format | Journal article |
| id | oxford-uuid:a3a24bb1-7733-4df7-b6ae-2c72db17b386 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T07:03:33Z |
| publishDate | 2022 |
| publisher | Bioscientifica |
| record_format | dspace |
| spelling | oxford-uuid:a3a24bb1-7733-4df7-b6ae-2c72db17b3862022-04-19T10:30:35ZMetformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesisJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:a3a24bb1-7733-4df7-b6ae-2c72db17b386EnglishSymplectic ElementsBioscientifica2022Green, CJMarjot, TWalsby-Tickle, JCharlton, CCornfield, TWestcott, FPinnick, KEMoolla, AHazlehurst, JMMcCullagh, JTomlinson, JWHodson, L<p><strong>Objective:</strong> Metformin is a first-line pharmacotherapy in the treatment of type 2 diabetes, a condition closely associated with NAFLD. Although metformin promotes weight loss and improves insulin sensitivity, its effect on intrahepatic triglyceride (IHTG) remains unclear. We investigated the effect of metformin on IHTG, hepatic de novo lipogenesis (DNL) and fatty acid (FA) oxidation in vivo in humans.</p> <p><strong>Design and Methods:</strong> Metabolic investigations, using stable-isotope tracers, were performed in 10 insulin-resistant, overweight/obese human participants with NAFLD who were treatment naïve before and after 12-weeks of metformin treatment. The effect of metformin on markers of subcutaneous adipose tissue FA metabolism and function, along with the plasma metabolome were investigated.</p> <p><strong>Results:</strong> Twelve weeks treatment with metformin resulted in a significant reduction in body weight and improved insulin sensitivity, but IHTG content and FA oxidation remained unchanged. Metformin treatment was associated with a significant decrease in VLDLtriglyceride (TG) concentrations and a significant increase in the relative contribution of DNL-derived FAs to VLDL-TG. There were subtle and relatively few changes in subcutaneous adipose tissue FA metabolism and the plasma metabolome with metformin treatment.</p> <p><strong>Conclusions:</strong> We demonstrate the mechanisms of action of metformin whereby it improves insulin sensitivity and promotes weight loss, without improvement in IHTG; these observations are partly, explained through increased hepatic DNL and a lack of change in fatty acid oxidation.</p> |
| spellingShingle | Green, CJ Marjot, T Walsby-Tickle, J Charlton, C Cornfield, T Westcott, F Pinnick, KE Moolla, A Hazlehurst, JM McCullagh, J Tomlinson, JW Hodson, L Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis |
| title | Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis |
| title_full | Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis |
| title_fullStr | Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis |
| title_full_unstemmed | Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis |
| title_short | Metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis |
| title_sort | metformin maintains intrahepatic triglyceride content through increased hepatic de novo lipogenesis |
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