The suprachiasmatic nucleus (SCN) in the mammalian hypothalamus functions as an endogenous pacemaker that generates and maintains circadian rhythms throughout the body. Next to this central clock, peripheral oscillators exist in almost all mammalian tissues. Whereas the SCN is mainly entrained to the environment by light, peripheral clocks are entrained by various factors, of which feeding/fasting is the most important. Desynchronization between the central and peripheral clocks by, for instance, altered timing of food intake can lead to uncoupling of peripheral clocks from the central pacemaker and is, in humans, related to the development of metabolic disorders, including obesity and Type 2 diabetes. Diets high in fat or sugar have been shown to alter circadian clock function. This review discusses the recent findings concerning the influence of nutrients, in particular fatty acids and glucose, on behavioral and molecular circadian rhythms and will summarize critical studies describing putative mechanisms by which these nutrients are able to alter normal circadian rhythmicity, in the SCN, in non-SCN brain areas, as well as in peripheral organs. As the effects of fat and sugar on the clock could be through alterations in energy status, the role of specific nutrient sensors will be outlined, as well as the molecular studies linking these components to metabolism. Understanding the impact of specific macronutrients on the circadian clock will allow for guidance toward the composition and timing of meals optimal for physiological health, as well as putative therapeutic targets to regulate the molecular clock.

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.