Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming
Background: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasi...
| Main Authors: | , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2017-08-01
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| Series: | Molecular Metabolism |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2212877817302867 |
| _version_ | 1818522743815012352 |
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| author | Adilson Guilherme David J. Pedersen Elizabeth Henchey Felipe S. Henriques Laura V. Danai Yuefei Shen Batuhan Yenilmez DaeYoung Jung Jason K. Kim Irfan J. Lodhi Clay F. Semenkovich Michael P. Czech |
| author_facet | Adilson Guilherme David J. Pedersen Elizabeth Henchey Felipe S. Henriques Laura V. Danai Yuefei Shen Batuhan Yenilmez DaeYoung Jung Jason K. Kim Irfan J. Lodhi Clay F. Semenkovich Michael P. Czech |
| author_sort | Adilson Guilherme |
| collection | DOAJ |
| description | Background: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood.
Methods & results: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT.
Conclusions: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT. |
| first_indexed | 2024-12-11T05:37:04Z |
| format | Article |
| id | doaj.art-6bc9d2917df04eb3b86d55ef045f6e28 |
| institution | Directory Open Access Journal |
| issn | 2212-8778 |
| language | English |
| last_indexed | 2024-12-11T05:37:04Z |
| publishDate | 2017-08-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Metabolism |
| spelling | doaj.art-6bc9d2917df04eb3b86d55ef045f6e282022-12-22T01:19:15ZengElsevierMolecular Metabolism2212-87782017-08-016878179610.1016/j.molmet.2017.05.012Adipocyte lipid synthesis coupled to neuronal control of thermogenic programmingAdilson Guilherme0David J. Pedersen1Elizabeth Henchey2Felipe S. Henriques3Laura V. Danai4Yuefei Shen5Batuhan Yenilmez6DaeYoung Jung7Jason K. Kim8Irfan J. Lodhi9Clay F. Semenkovich10Michael P. Czech11Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USADivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USADivision of Endocrinology, Metabolism and Lipid Research, Washington University School of Medicine, St. Louis, MO 63110, USAProgram in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA 01605, USABackground: The de novo biosynthesis of fatty acids (DNL) through fatty acid synthase (FASN) in adipocytes is exquisitely regulated by nutrients, hormones, fasting, and obesity in mice and humans. However, the functions of DNL in adipocyte biology and in the regulation of systemic glucose homeostasis are not fully understood. Methods & results: Here we show adipocyte DNL controls crosstalk to localized sympathetic neurons that mediate expansion of beige/brite adipocytes within inguinal white adipose tissue (iWAT). Induced deletion of FASN in white and brown adipocytes of mature mice (iAdFASNKO mice) enhanced glucose tolerance, UCP1 expression, and cAMP signaling in iWAT. Consistent with induction of adipose sympathetic nerve activity, iAdFASNKO mice displayed markedly increased neuronal tyrosine hydroxylase (TH) and neuropeptide Y (NPY) content in iWAT. In contrast, brown adipose tissue (BAT) of iAdFASNKO mice showed no increase in TH or NPY, nor did FASN deletion selectively in brown adipocytes (UCP1-FASNKO mice) cause these effects in iWAT. Conclusions: These results demonstrate that downregulation of fatty acid synthesis via FASN depletion in white adipocytes of mature mice can stimulate neuronal signaling to control thermogenic programming in iWAT.http://www.sciencedirect.com/science/article/pii/S2212877817302867Adipocytesde novo lipogenesisiWAT browningGlucose homeostasisSympathetic nerve activation |
| spellingShingle | Adilson Guilherme David J. Pedersen Elizabeth Henchey Felipe S. Henriques Laura V. Danai Yuefei Shen Batuhan Yenilmez DaeYoung Jung Jason K. Kim Irfan J. Lodhi Clay F. Semenkovich Michael P. Czech Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming Molecular Metabolism Adipocytes de novo lipogenesis iWAT browning Glucose homeostasis Sympathetic nerve activation |
| title | Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming |
| title_full | Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming |
| title_fullStr | Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming |
| title_full_unstemmed | Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming |
| title_short | Adipocyte lipid synthesis coupled to neuronal control of thermogenic programming |
| title_sort | adipocyte lipid synthesis coupled to neuronal control of thermogenic programming |
| topic | Adipocytes de novo lipogenesis iWAT browning Glucose homeostasis Sympathetic nerve activation |
| url | http://www.sciencedirect.com/science/article/pii/S2212877817302867 |
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