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http://en.wikipedia.org/wiki/Oxyntomodulin is a hormone AND
IS ALSO used as a drug. The free-to-all
full-text (1) paper may illustrate the science of
oxyntomodulin relative to
our consumption level in further detail. Oxyntomodulin acts
independently
of the related
http://en.wikipedia.org/wiki/Glucagon-like_peptide-1 hormone,
apparently. A more recent (2) paper failed to provide the
details of the effects on reduced intake level associated
with oxyntomodulin
peripheral exposure. Taking hormones via routes other than
those such as
injected into specific brain areas may render the agent to
be of greater
potential pharmacological utility. An earlier
free-full-text (3) paper from
the authors of the (2) paper utilized 50% CR, it seemed, to
study what may
have been the same mouse strain.

1. Baggio LL, Huang Q, Brown TJ, Drucker DJ.
Oxyntomodulin and glucagon-like peptide-1 differentially
regulate murine
food intake and energy expenditure.
Gastroenterology. 2004 Aug;127(2):546-58.
PMID: 15300587

BACKGROUND & AIMS: Gut-derived peptides including
ghrelin,
cholecystokinin (CCK), peptide YY (PYY), glucagon-like
peptide (GLP-1), and
GLP-2 exert overlapping actions on energy homeostasis
through defined
G-protein-coupled receptors (GPCRs). The proglucagon-derived
peptide (PGDP)
oxyntomodulin (OXM) is cosecreted with GLP-1 and inhibits
feeding in rodents
and humans; however, a distinct receptor for OXM has not
been identified.
METHODS: We examined the mechanisms mediating oxyntomodulin
action using
stable cell lines expressing specific PGDP receptors in
vitro and both
wild-type and knockout mice in vivo. RESULTS: OXM activates
signaling
pathways in cells through glucagon or GLP-1 receptors
(GLP-1R) but
transiently inhibits food intake in vivo exclusively through
the GLP-1R.
Both OXM and the GLP-1R agonist exendin-4 (Ex-4) activated
neuronal c-fos
expression in the paraventricular nucleus of the
hypothalamus, the area
postrema, and the nucleus of the solitary tract following
intraperitoneal
(i.p.) injection. However, OXM transiently inhibited food
intake in
wild-type mice following intracerebroventricular (i.c.v.)
but not i.p.
administration, whereas Ex-4 produced a more potent and
sustained inhibition
of food intake following both i.c.v. and i.p.
administration. The anorectic
effects of OXM were preserved in Gcgr(-/-) mice but
abolished in GLP-1R(-/-)
mice. Although central Ex-4 and OXM inhibited feeding via a
GLP-1R-dependent
mechanism, Ex-4 but not OXM reduced VO2 and respiratory
quotient in
wild-type mice. Conclusions: These findings demonstrate that
structurally
distinct PGDPs differentially regulate food intake and
energy expenditure by
interacting with a GLP-1R-dependent pathway. Hence
ligand-specific
activation of a common GLP-1R increases the complexity of
gut-central
nervous system pathways regulating energy homeostasis and
metabolic
expenditure.

2. Sowden GL, Drucker DJ, Weinshenker D, Swoap SJ.
Oxyntomodulin increases intrinsic heart rate in mice
independent of the
glucagon-like peptide-1 receptor.
Am J Physiol Regul Integr Comp Physiol. 2006 Oct 12; [Epub
ahead of print]
PMID: 17038440

Oxyntomodulin (OXM), a postprandially released
intestinal hormone,
inhibits food intake via the glucagon-like peptide-1
receptor (GLP-1R).
While OXM may have clinical value in treating obesity, the
cardiovascular
effects of OXM are not well understood. Using telemetry to
measure heart
rate (HR), body temperature (Tb) and activity in conscious
and freely moving
mice, we tested 1) whether OXM affects HR, and 2) whether
this effect is
mediated by the GLP-1R. We found that peripherally
administered OXM
significantly increased HR in wildtype mice, raising HR by
over 200 bpm to a
maximum of 728 +/- 11 bpm. To determine the extent to which
the sympathetic
nervous system (SNS) mediates the tachycardia of OXM, this
hormone was
delivered to mice deficient in dopamine beta hydroxylase
(Dbh -/- mice),
littermate controls (Dbh +/- mice), and
autonomically-blocked C57Bl mice.
OXM increased HR equally in all groups (192 +/- 13, 197 +/-
21, 216 +/- 11
bpm, respectively), indicating that OXM elevated intrinsic
HR. Intrinsic HR
was also vigorously elevated by OXM in Glp-1R -/- mice (200
+/- 28 bpm). In
addition, peripherally-administered OXM inhibited food
intake and activity
levels in wildtype mice, and lowered Tb in autonomically
blocked mice. None
of these effects were observed in Glp-1R -/- mice. These
data suggest
multiple modes of action of OXM: 1) it directly elevates
murine intrinsic HR
through a GLP-1R independent mechanism, perhaps via the
glucagon receptor or
an unidentified OXM receptor, and 2) it lowers food intake,
activity, and Tb
in a GLP-1R dependent fashion.

3. Swoap SJ, Weinshenker D, Palmiter RD, Garber G.
Dbh(-/-) mice are hypotensive, have altered circadian
rhythms, and have
abnormal responses to dieting and stress.
Am J Physiol Regul Integr Comp Physiol. 2004
Jan;286(1):R108-13. Epub 2003
Sep 11.
PMID: 12969876