cron-web.org

[A1CR]

CRers may be governed by their
http://en.wikipedia.org/wiki/Circadian_rhythms and CR may
alter these
biological clocks of ours. The paper below appeared to
focus on the subject that may most be in our interest and
the majority of the text appeared to be of no interest.

Annual Review of Genetics 40:409-48 (Dec 2006)
Interplay of Circadian Clocks and Metabolic Rhythms
Herman Wijnen and Michael W. Young

This review examines the connections between circadian and
metabolic
rhythms. Examples from a wide variety of well-studied
organisms are used to
illustrate some of the genetic and molecular pathways
linking circadian
timekeeping to metabolism. The principles underlying
biological timekeeping
by intrinsic circadian clocks are discussed briefly. Genetic
and molecular
studies have unambiguously identified the importance of gene
expression
feedback circuits to the generation of overt circadian
rhythms. This is
illustrated particularly well by the results of genome-wide
expression
studies, which have uncovered hundreds of clock-controlled
genes in
cyanobacteria, fungi, plants, and animals. The potential
connections between
circadian oscillations in gene expression and circadian
oscillations in
metabolic activity are a major focus of this review.

... The mammalian clock circuits also consist of two
feedback loops
connected by a central pair of bHLH-PAS domain transcription
factors
(CLOCK/BMAL1 or NPAS2/BMAL1). ... food-entrained oscillator
(FEO) ... a
central pacemaker tissue in the suprachiasmatic nucleus
(SCN) of the
hypothalamus ... NPAS2 may also serve to couple cellular
redox rhythms to
the circadian cycle as it is thought to bind nicotinamide
adenine
dinucleotide (NAD) via its bHLH domain. The redox state of
bound NAD(P)
moieties was shown to control in vitro binding activity of
NPAS2-BMAL1
complexes, suggesting a possible mechanism for metabolic
entrainment of the
circadian clock via cellular redox oscillations (208).
Restricted feeding of
rodents entrains the circadian clocks in their livers and
several other
organs independently from the light-entrained oscillator in
the SCN, and
food-induced changes in redox state may possibly contribute
to entrainment
of the clock circuits in organs such as the liver (41, 78,
230). An
alternative theory postulates that alterations in the daily
profile of body
temperature observed as a result of restrictive feeding may
contribute to
the resetting of peripheral circadian clocks (23, 41).
Because the effect of
restrictive feeding protocols on food-anticipatory locomotor
activity (FAA)
is longer-lived than that on circadian expression rhythms in
peripheral
digestive organs, a food-entrained oscillator (FEO) may
reside elsewhere
(43). Early studies showed that FAA persists in SCN-lesioned
animals,
excluding the SCN as the sole site of the FEO (130, 228,
229). As the FEO
remains functional in CLOCK homozygous mutant mice, one
possibility is that
it corresponds to a brain pacemaker tissue that
preferentially expresses
NPAS2, instead of CLOCK itself (192). The dorsomedial
nucleus of the
hypothalamus (DMH) was recently reported to play an
important role in
controlling FAA (70). It is not likely, however, that the
DMH represents the
sole site of the FEO (136). When restrictive feeding
protocols are applied
out of phase with light-entrained activity rhythms,
resetting of peripheral
clocks is slow, whereas a subsequent reversal in entrainment
by restrictive
feeding in the opposite phase occurs much more quickly
(137). These
observations are explained by the role of glucocorticoids as
SCN-controlled
synchronizers. SCN-mediated inhibition of entrainment to
restricted feeding
protocols is much reduced in the absence of either the
glucocorticoid
receptor in the liver or the adrenal glands, which are
responsible for
glucocorticoid secretion (137). Many of the circadian
oscillations in gene
expression in the liver do in fact depend on adrenal
glucocorticoid signals
(181). A recent study demonstrated that, in addition to the
hypothalamic-pituitary-adrenal axis, an alternative neural
pathway can also
mediate SCN-regulation of adrenal glucocorticoid release,
with the latter
providing a more immediate response to environmental light
(104). ...