Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice
Objective: Medium chain fatty acids (MCFAs), which are fatty acids with chain lengths of 8–12 carbon atoms, have been shown to reduce food intake in rodents and humans, but the underlying mechanisms are unknown. Unlike most other fatty acids, MCFAs are absorbed from the intestine into the portal vei...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2023-08-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877823000947 |
| _version_ | 1797779190012968960 |
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| author | Josephine M. Kanta Luisa Deisen Kornelia Johann Stephanie Holm Annemarie Lundsgaard Jens Lund Markus Jähnert Annette Schürmann Christoffer Clemmensen Bente Kiens Andreas M. Fritzen Maximilian Kleinert |
| author_facet | Josephine M. Kanta Luisa Deisen Kornelia Johann Stephanie Holm Annemarie Lundsgaard Jens Lund Markus Jähnert Annette Schürmann Christoffer Clemmensen Bente Kiens Andreas M. Fritzen Maximilian Kleinert |
| author_sort | Josephine M. Kanta |
| collection | DOAJ |
| description | Objective: Medium chain fatty acids (MCFAs), which are fatty acids with chain lengths of 8–12 carbon atoms, have been shown to reduce food intake in rodents and humans, but the underlying mechanisms are unknown. Unlike most other fatty acids, MCFAs are absorbed from the intestine into the portal vein and enter first the liver. We thus hypothesized that MCFAs trigger the release of hepatic factors that reduce appetite. Methods: The liver transcriptome in mice that were orally administered MCFAs as C8:0 triacylglycerol (TG) was analyzed. Circulating growth/differentiation factor 15 (GDF15), tissue Gdf15 mRNA and food intake were investigated after acute oral gavage of MCFAs as C8:0 or C10:0 TG in mice. Effects of acute and subchronic administration of MCFAs as C8:0 TG on food intake and body weight were determined in mice lacking either the receptor for GDF15, GDNF Family Receptor Alpha Like (GFRAL), or GDF15. Results: Hepatic and small intestinal expression of Gdf15 and circulating GDF15 increased after ingestion of MCFAs, while intake of typical dietary long-chain fatty acids (LCFAs) had no effect. Plasma GDF15 levels also increased in the portal vein with MCFA intake, indicating that in addition to the liver, the small intestine contributes to the rise in circulating GDF15. Acute oral provision of MCFAs decreased food intake over 24 h compared with a LCFA-containing bolus, and this anorectic effect required the GDF15 receptor, GFRAL. Moreover, subchronic oral administration of MCFAs reduced body weight over 7 days, an effect that was blunted in mice lacking either GDF15 or GFRAL. Conclusions: We have identified ingestion of MCFAs as a novel nutritional approach that increases circulating GDF15 in mice and have revealed that the GDF15-GFRAL axis is required for the full anorectic effect of MCFAs. |
| first_indexed | 2024-03-12T23:27:07Z |
| format | Article |
| id | doaj.art-5dd29cdca916406fad79610195385845 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-03-12T23:27:07Z |
| publishDate | 2023-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-5dd29cdca916406fad796101953858452023-07-16T04:18:31ZengElsevierMolecular Metabolism2212-87782023-08-0174101760Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in miceJosephine M. Kanta0Luisa Deisen1Kornelia Johann2Stephanie Holm3Annemarie Lundsgaard4Jens Lund5Markus Jähnert6Annette Schürmann7Christoffer Clemmensen8Bente Kiens9Andreas M. Fritzen10Maximilian Kleinert11The August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, DenmarkMuscle Physiology and Metabolism Group, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, GermanyMuscle Physiology and Metabolism Group, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 Munich, GermanyNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkThe August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, DenmarkNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkGerman Center for Diabetes Research (DZD), 85764 Munich, Germany; Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), 14558 Potsdam, GermanyGerman Center for Diabetes Research (DZD), 85764 Munich, Germany; Department of Experimental Diabetology, German Institute of Human Nutrition (DIfE), 14558 Potsdam, Germany; Institute of Nutrition Science, University of Potsdam, Nuthetal, Germany; Faculty of Health Sciences, Joint Faculty of the Brandenburg University of Technology Cottbus-Senftenberg, The Brandenburg Medical School Theodor Fontane and The University of Potsdam, 14469 Potsdam, GermanyNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, DenmarkThe August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, DenmarkThe August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; Corresponding author. Department of Biomedical Sciences, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark.The August Krogh Section of Molecular Physiology, Department of Nutrition, Exercise and Sports, Faculty of Science, University of Copenhagen, Copenhagen, Denmark; Muscle Physiology and Metabolism Group, German Institute of Human Nutrition (DIfE), Potsdam-Rehbruecke, Nuthetal, Germany; German Center for Diabetes Research (DZD), 85764 Munich, Germany; Corresponding author. German Institute of Human Nutrition Potsdam-Rehbruecke, Arthur-Scheunert-Allee 114-116, 14558 Nuthetal, Germany.Objective: Medium chain fatty acids (MCFAs), which are fatty acids with chain lengths of 8–12 carbon atoms, have been shown to reduce food intake in rodents and humans, but the underlying mechanisms are unknown. Unlike most other fatty acids, MCFAs are absorbed from the intestine into the portal vein and enter first the liver. We thus hypothesized that MCFAs trigger the release of hepatic factors that reduce appetite. Methods: The liver transcriptome in mice that were orally administered MCFAs as C8:0 triacylglycerol (TG) was analyzed. Circulating growth/differentiation factor 15 (GDF15), tissue Gdf15 mRNA and food intake were investigated after acute oral gavage of MCFAs as C8:0 or C10:0 TG in mice. Effects of acute and subchronic administration of MCFAs as C8:0 TG on food intake and body weight were determined in mice lacking either the receptor for GDF15, GDNF Family Receptor Alpha Like (GFRAL), or GDF15. Results: Hepatic and small intestinal expression of Gdf15 and circulating GDF15 increased after ingestion of MCFAs, while intake of typical dietary long-chain fatty acids (LCFAs) had no effect. Plasma GDF15 levels also increased in the portal vein with MCFA intake, indicating that in addition to the liver, the small intestine contributes to the rise in circulating GDF15. Acute oral provision of MCFAs decreased food intake over 24 h compared with a LCFA-containing bolus, and this anorectic effect required the GDF15 receptor, GFRAL. Moreover, subchronic oral administration of MCFAs reduced body weight over 7 days, an effect that was blunted in mice lacking either GDF15 or GFRAL. Conclusions: We have identified ingestion of MCFAs as a novel nutritional approach that increases circulating GDF15 in mice and have revealed that the GDF15-GFRAL axis is required for the full anorectic effect of MCFAs.http://www.sciencedirect.com/science/article/pii/S2212877823000947Medium-chain fatty acidsGrowth/differentiation factor 15SatietyLipid metabolismFood intakeHepatokine |
| spellingShingle | Josephine M. Kanta Luisa Deisen Kornelia Johann Stephanie Holm Annemarie Lundsgaard Jens Lund Markus Jähnert Annette Schürmann Christoffer Clemmensen Bente Kiens Andreas M. Fritzen Maximilian Kleinert Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice Molecular Metabolism Medium-chain fatty acids Growth/differentiation factor 15 Satiety Lipid metabolism Food intake Hepatokine |
| title | Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice |
| title_full | Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice |
| title_fullStr | Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice |
| title_full_unstemmed | Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice |
| title_short | Dietary medium-chain fatty acids reduce food intake via the GDF15-GFRAL axis in mice |
| title_sort | dietary medium chain fatty acids reduce food intake via the gdf15 gfral axis in mice |
| topic | Medium-chain fatty acids Growth/differentiation factor 15 Satiety Lipid metabolism Food intake Hepatokine |
| url | http://www.sciencedirect.com/science/article/pii/S2212877823000947 |
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