The circadian system comprises a central clock, which is located in the SCN of the hypothalamus, and a series of peripheral clocks located in tissues throughout the body. The central clock is entrained primarily by light, and its rhythm is measured through frequent sampling of melatonin, cortisol, or core body temperature. The central clock affects the phases and amplitudes of peripheral clocks through hormones and synaptic projections. The peripheral clocks are entrained by a combination of these signals from the central clock and external factors, most notably the timing of food intake. Peripheral clock rhythms are measured in humans either by directly measuring the rhythm in a physiologic variable or by measuring the expression of clock genes. Overall, daily rhythms in metabolism are produced by the central and peripheral clocks working in concert.