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including those affecting circadian rhythms also play pivotal roles in meta-
bolic homeostasis. 68,69 Because today's technology provides exogenous
lighting throughout the 24-h cycle, night shift and rotating shift work have
become increasingly common. These extensions of the conventional work-
day influence not only temporal aspects of work and social activities but also
physiological and molecular rhythms in the body. Studies on night shift and
rotating shift workers present compelling evidence that circadian rhythm
disruptions contribute to metabolic disorders. For example, an association
between cardiovascular disease, increased body mass, and elevated plasma
glucose and lipid levels has been observed in circadian disturbance and
humans which engage in nighttime shift work. 70-73 Small rodent studies also
support this link and simply changing their normal light/dark cycle to one in
which dim light replaces the normal dark period causes profound changes in
metabolism that are observed on a physiological level. 74
Integral to cellular metabolism are small metabolites. Metabolites are
gaining attention based on their potent zeitgeber effects on some tissues.
Many small metabolites are used for epigenetic processes. Specifically, bio-
chemicals such as S -adenosyl methionine, citrate, acetyl-CoA, NAD รพ ,
GlcNAc, glucose, glutamine, methionine, and ATP are all direct or indirect
modulators of chromatin structure (see Fig. 2.3 ). In part because of this,
recent studies have begun to focus on more global oscillations within the
Figure 2.3 Metabolites affectmodifications at histone tails andact as substrates, cofactors,
or upstreammetabolic precursors for the many modifications at histone tails. Me, methyl-
ation; P, phosphorylation; Ac, acetylation; Ub, ubiquitination; Gly, glycosylation.
 
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