Differential effects of omega-3 fatty acid docosahexaenoic acid and palmitate on the circadian transcriptional profile of clock genes in immortalized hypothalamic neurons

Aug 22, 2014American journal of physiology. Regulatory, integrative and comparative physiology

Different effects of omega-3 and saturated fats on daily gene activity in brain cells controlling body rhythms

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Abstract

25 μM of palmitate significantly increased the transcriptional expression of Bmal1.

Diets high in saturated fatty acids are linked to circadian dysregulation, obesity, and Type 2 diabetes.
Polyunsaturated fatty acids may improve insulin sensitivity and reduce weight gain.
The immortalized murine neuronal model, mHypoE-37, expresses key clock genes in a circadian manner.
Palmitate increases Bmal1 expression without affecting certain inflammatory markers or orexigenic neuropeptides.
DHA alters the circadian expression profile of Bmal1 differently than palmitate.
DHA may mitigate the disruptive effects of palmitate on circadian parameters.

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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.

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Differential effects of omega-3 fatty acid docosahexaenoic acid and palmitate on the circadian transcriptional profile of clock genes in immortalized hypothalamic neurons

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