Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe
The ChREBP/Mondo-Mlx transcription factors are activated by sugars and are essential for sugar tolerance. They promote the conversion of sugars to lipids, but beyond this, their physiological roles are insufficiently understood. Here, we demonstrate that in an organism-wide setting in Drosophila, Mo...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2015-10-01
|
| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715009948 |
| _version_ | 1828908656392929280 |
|---|---|
| author | Jaakko Mattila Essi Havula Erja Suominen Mari Teesalu Ida Surakka Riikka Hynynen Helena Kilpinen Juho Väänänen Iiris Hovatta Reijo Käkelä Samuli Ripatti Thomas Sandmann Ville Hietakangas |
| author_facet | Jaakko Mattila Essi Havula Erja Suominen Mari Teesalu Ida Surakka Riikka Hynynen Helena Kilpinen Juho Väänänen Iiris Hovatta Reijo Käkelä Samuli Ripatti Thomas Sandmann Ville Hietakangas |
| author_sort | Jaakko Mattila |
| collection | DOAJ |
| description | The ChREBP/Mondo-Mlx transcription factors are activated by sugars and are essential for sugar tolerance. They promote the conversion of sugars to lipids, but beyond this, their physiological roles are insufficiently understood. Here, we demonstrate that in an organism-wide setting in Drosophila, Mondo-Mlx controls the majority of sugar-regulated genes involved in nutrient digestion and transport as well as carbohydrate, amino acid, and lipid metabolism. Furthermore, human orthologs of the Mondo-Mlx targets display enrichment among gene variants associated with high circulating triglycerides. In addition to direct regulation of metabolic genes, Mondo-Mlx maintains metabolic homeostasis through downstream effectors, including the Activin ligand Dawdle and the Gli-similar transcription factor Sugarbabe. Sugarbabe controls a subset of Mondo-Mlx-dependent processes, including de novo lipogenesis and fatty acid desaturation. In sum, Mondo-Mlx is a master regulator of other sugar-responsive pathways essential for adaptation to a high-sugar diet. |
| first_indexed | 2024-12-13T18:13:09Z |
| format | Article |
| id | doaj.art-bc787bf3a50e4994b72aac3c86df2c22 |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T18:13:09Z |
| publishDate | 2015-10-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-bc787bf3a50e4994b72aac3c86df2c222022-12-21T23:35:54ZengElsevierCell Reports2211-12472015-10-0113235036410.1016/j.celrep.2015.08.081Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor SugarbabeJaakko Mattila0Essi Havula1Erja Suominen2Mari Teesalu3Ida Surakka4Riikka Hynynen5Helena Kilpinen6Juho Väänänen7Iiris Hovatta8Reijo Käkelä9Samuli Ripatti10Thomas Sandmann11Ville Hietakangas12Department of Biosciences, University of Helsinki, Helsinki 00790, FinlandDepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandDepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandDepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00270, FinlandDepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandEMBL-EBI, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SD, UKDepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandDepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandDepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandInstitute for Molecular Medicine Finland (FIMM), University of Helsinki, Helsinki 00270, FinlandDepartment of Bioinformatics and Computational Biology, Genentech Inc., South San Francisco, CA 94080, USADepartment of Biosciences, University of Helsinki, Helsinki 00790, FinlandThe ChREBP/Mondo-Mlx transcription factors are activated by sugars and are essential for sugar tolerance. They promote the conversion of sugars to lipids, but beyond this, their physiological roles are insufficiently understood. Here, we demonstrate that in an organism-wide setting in Drosophila, Mondo-Mlx controls the majority of sugar-regulated genes involved in nutrient digestion and transport as well as carbohydrate, amino acid, and lipid metabolism. Furthermore, human orthologs of the Mondo-Mlx targets display enrichment among gene variants associated with high circulating triglycerides. In addition to direct regulation of metabolic genes, Mondo-Mlx maintains metabolic homeostasis through downstream effectors, including the Activin ligand Dawdle and the Gli-similar transcription factor Sugarbabe. Sugarbabe controls a subset of Mondo-Mlx-dependent processes, including de novo lipogenesis and fatty acid desaturation. In sum, Mondo-Mlx is a master regulator of other sugar-responsive pathways essential for adaptation to a high-sugar diet.http://www.sciencedirect.com/science/article/pii/S2211124715009948 |
| spellingShingle | Jaakko Mattila Essi Havula Erja Suominen Mari Teesalu Ida Surakka Riikka Hynynen Helena Kilpinen Juho Väänänen Iiris Hovatta Reijo Käkelä Samuli Ripatti Thomas Sandmann Ville Hietakangas Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe Cell Reports |
| title | Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe |
| title_full | Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe |
| title_fullStr | Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe |
| title_full_unstemmed | Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe |
| title_short | Mondo-Mlx Mediates Organismal Sugar Sensing through the Gli-Similar Transcription Factor Sugarbabe |
| title_sort | mondo mlx mediates organismal sugar sensing through the gli similar transcription factor sugarbabe |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715009948 |
| work_keys_str_mv | AT jaakkomattila mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT essihavula mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT erjasuominen mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT mariteesalu mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT idasurakka mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT riikkahynynen mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT helenakilpinen mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT juhovaananen mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT iirishovatta mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT reijokakela mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT samuliripatti mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT thomassandmann mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe AT villehietakangas mondomlxmediatesorganismalsugarsensingthroughtheglisimilartranscriptionfactorsugarbabe |