Hypothalamic nuclei

The intention is merely to give a brief overview of the role of

hypothalamic areas which are known (at this point in time!) to be
involved with energy balance, and their interaction with peptides
produced in other areas of the body.
The Hypothalamus and the Dorsal Vagal complex together are involved
in the regulation of appetite and hence the fat mass. While the Lateral
Hypothalamic nucleus along with the peri-fornical area is implicated in
positive energy balance (increased appetite), Brain Res. 1993 Dec
10;630(1-2):41-9 the paraventricular (PVN), dorsomedian (DMN), and
paramedian (PMN) nuclei are involved in circuitry that decrease
appetite. Signalling between these two different sets of nuclei are
integrated by the Arcuate nucleus of the hypothalamus. The Arcuate
nucleus is conveniently located at the floor of the third ventricle in an
area without the blood brain barrier. This facilitates signalling from the
peripheries (intestines and adipose tissue) to reach the relevant nuclei
via the Arcuate nucleus.
The Arcuate nucleus produces neuropeptides which are either
orexigenic (appetite promoting) or anorexigenic (appetite decreasing).
Neuropeptide Y (NPY) and Agouti Related Peptide (AgRP) work together
as orexigenic peptides, while alpha MSH ( Melanocyte stimulating
hormone) and Cocaine Amphetamine related Transcript (CART) function
as anorexigenic peptides. Other peptides favouring an orexigenic
( Orexins, Galanin, Cannabinoids, Melanocyte concentrating hormoneMCH) or anorexigenic (Neurotensin, Urocortin/CRH, Serotonin,
Cholecystokinin) behaviour are also produced or present in the
hypothalamic nuclei. Peripheral signals from the gut may act on the
NPY/AgRP pathway (Ghrelin) to facilitate energy intake, while other gut
hormones (Peptide YY, Cholecystokinin, GLP-1, Oxyntomodulin) act on
the Arcuate nucleus to facilitate a reduction in energy intake. Peptides
from the adipose tissue (Leptin) influence both orexigenic and
anorexigenic peptides depending on the body (fat) composition or
energy state to bring about alterations in behaviour to maintain fat
mass, predominantly concerned with ensuring adequate fat stores.
While these networks in the hypothalamus are being increasingly
clarified, the importance of the brainstem areas in appetite regulation
is also being recognised. POMC immunoreactivity (melanocortin
system) has been described in the nucleus of tractus solitarius and
other nuclei, and they communicate with the hypothalamic
melanocortin system to bring about appetite modulation.
Thus, while the predominant concept is that the Arcuate nucleus by
virtue of its lack of blood brain barrier receives and relays signals from

the peripheral organs, the vagal nuclei also facilitate communication

between the peripheries and the hypothalamic nuclei. The Dorsal Vagal
complex consist of the nucleus of tractus solitarius (NTS), Dorsal Motor
nucleus of Vagus (DMV) and area postrema (AP). Vagal afferents carry
primary sensory information from the gastrointestinal tract to the
neurons in the NTS and AP. The NTS processes these sensory inputs
and sends axonal projections to the subjacent DMN. Vagal efferents
from the DMN project to enteric neurons in the gastrointestinal tract
and pancreas effecting a variety of gastrointestinal actions modulating
gastric emptying, gastric motility and pancreatic secretions.
Interruption of vagal transmission (surgically or pharmacologically) has
been shown to result in blockade of the actions of peripherally injected
peptides, suggesting the role of the vagus in mediating the central
transport of peripherally produced impulses. The dorsomedial region of
the NTS has fenestrated capillaries that allow circulating peptides to
access the NTS and neighbouring DMN, further facilitating
communication between the gut and brain.
Thus, while some hypothalamic nuclei sense and relay energy status,
other nuclei send signals to initiate appetite. But motor activity need to
be initiated to respond to this appetite with resultant food
procurement. Food stimulates dopamine release in the nucleus
accumbens from neurons that project from the ventromedial nucleus to
the nucleus accumbens. This dopamine release in the nucleus
accumbens is thought to play a role in behavioural modification with
motor responses that aim to facilitate appetite quenching through
quest for food and food ingestion. Brain Res Brain Res Rev. 1999
Dec;31(1):6-41. The Nucleus Accumbens contains a high density of
CB1 (Cannabinoid receptor-1) receptors, through which endogenous
cannabinoids may influence feeding related activity. The central
nucleus of amygdala is being increasingly recognised to be important
in ingestive responses. Direct projections from the nucleus of
amygdala to the PVN have been described, as well as connections with
the Nucleus of tractus solitarius and DMV (dorsal motor nucleus of
vagus). J Comp Neurol. 1984 Mar 20;224(1):1-24.

Activation of the hypothalamo-pituitary-adrenal axis and the Growth

hormone-IGF-1 axis induce a positive energy balance while the
hypothalamo-pituitary-thyroid axis activation produces negative
energy balance through increased BMR. The PVN is sensitive to the
actions of glucocorticoids secreted by the adrenal cortex, Diabetes.
1999 Feb;48(2):365-70. and it may effectively function in conjunction
with the hypothalamo-pituitary-adrenal axis. The hypothalamopituitary-ovarian axis induces a negative energy balance in women.