Differential effects of omega-3 fatty acid docosahexaenoic acid and palmitate on the circadian transcriptional profile of clock genes in immortalized hypothalamic neurons
| Autor: | Denise D. Belsham, James A Greco, Johanneke E. Oosterman |
|---|---|
| Přispěvatelé: | AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Endocrinology, Graduate School |
| Rok vydání: | 2014 |
| Předmět: |
medicine.medical_specialty
Docosahexaenoic Acids Physiology Circadian clock Hypothalamus Palmitates Biology AMP-Activated Protein Kinases Cell Line Glycogen Synthase Kinase 3 Mice Physiology (medical) Internal medicine Circadian Clocks medicine Animals Phosphorylation Omega 3 fatty acid Unsaturated fatty acid Cells Cultured chemistry.chemical_classification Neurons Glycogen Synthase Kinase 3 beta Neural Control food and beverages ARNTL Transcription Factors Period Circadian Proteins Circadian Rhythm PER2 Endocrinology chemistry Docosahexaenoic acid Saturated fatty acid Models Animal Nuclear Receptor Subfamily 1 Group D Member 1 lipids (amino acids peptides and proteins) Transcriptome Polyunsaturated fatty acid |
| Zdroj: | American journal of physiology. Regulatory, integrative and comparative physiology, 307(8), R1049-R1060. American Physiological Society |
| ISSN: | 1522-1490 0363-6119 |
| Popis: | Diets high in saturated fatty acids (SFAs) are associated with the development of circadian dysregulation, obesity, and Type 2 diabetes mellitus. Conversely, polyunsaturated fatty acids (PUFAs) have recently been identified to improve insulin sensitivity, reduce weight gain, and relieve obesity-induced inflammation. While saturated fatty acids, such as the prevalent dietary fatty acid palmitate, have been implicated in circadian disruption, there is a paucity of studies regarding the effects of PUFAs on circadian parameters. Therefore, the immortalized murine neuronal model, mHypoE-37, was utilized to examine the effects of the SFA palmitate and omega-3 PUFA docosahexaenoic acid (DHA) on circadian rhythms. The mHypoE-37 neurons express the core clock genes, Bmal1, Per2, and Rev-erbα, in a circadian manner. 25 μM of palmitate significantly increased the transcriptional expression of Bmal1, without altering the expression of inflammatory markers TLR4, IκBα, and IL-6, nor the orexigenic neuropeptide AgRP, suggesting that the observed disruption of the molecular clock is the result of a mechanism distinct from that of hypothalamic cellular inflammation. Furthermore, treatment with the PUFA DHA resulted in alterations in the circadian expression profile of Bmal1, although differentially from the effects of palmitate. In the presence of DHA, the disruptive effects of palmitate on Bmal1 were less pronounced, suggesting a protective effect of DHA. These studies are the first to identify the potential for omega-3 PUFAs to protect against palmitate-mediated dysregulation of circadian parameters and will ultimately improve the understanding of circadian control mechanisms. |
| Databáze: | OpenAIRE |
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