Transcript Feeding Regulation

Hypothalamus
BLOCK 3 – 2011-12
Robert R. Terreberry, PhD
Room 142 Ph 864.327.9827
[email protected]
Hypothalamic Zones
Mid-sagittal
FORNIX
Hypothalamus
Scheme
ANTERIOR
OPTIC CHIASM
SUPRAOPTIC
ZONE
midline
TUBERAL
ZONE
MEDIAN
EMINENCE
MAMILLARY
ZONE
LATERAL
POSTERIOR
LATERAL
REGION
MAMILLARY
BODY
MEDIAL
MEDIAL
REGION
Hypothalamus Levels
Supraoptic Zone
Tuberal Zone
Mamillary Zone
Hypothalamic Afferents
Hypothalamic Efferents
Hypothalamus Connections
CEREBRAL
CORTEX
THALAMUS
HIPPOCAMPUS
SUBICULUM
MTT
FORNIX
DLF
RETINA
BRAINSTEM
HYPOTHALAMUS
HAT
MFB
OLFACT. SYST.
SEPTUM
ST
VAF
AMYGDALA
HYPOPHYSIS
Pituitary Gland
Neural
Portal
Herring body
Hypothalamus
Scheme
FORNIX
ANTERIOR
OPTIC CHIASM
SUPRAOPTIC
ZONE
midline
TUBERAL
ZONE
MEDIAN
EMINENCE
MAMILLARY
ZONE
LATERAL
POSTERIOR
LATERAL
REGION
MAMILLARY
BODY
MEDIAL
MEDIAL
REGION
Functional Areas
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Parasympathetic Areas
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Sympathetic Areas
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Temperature Regulation
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Temperature Regulation
Circadian
Fluctuation in Core Body Temperature
37.6
Body Temperature (°C)
37.4
37.2
37
36.8
36.6
36.4
36.2
36
4 a.m.
8 a.m.
1 p.m.
4 p.m.
8 p.m.
12 p.m.
4 a.m.
Temperature Regulation
 Temperature affects Ant. Hypothalamus /
Preoptic Area
• Promote Heat Loss • Prevent Heat Production
• Sweating
• Vasodilation
• Behavioral ’s
•  muscle tone / activity
•  thyroid hormone / epinephrine
•  appetite (calories)
Temperature Regulation
 Temperature affects Post. Hypothalamus
• Promote Heat Production
• Shivering,  muscle tone
•  thyroid hormone / epinephrine
• Prevent Heat Loss
• Vasoconstriction
• Behavioral ’s
Temperature Regulation
Lesion of Anterior Hypothalamus
• Inability to lower body temperature
• Hyperthermia in a hot environment
• 41˚C (106˚F) – convulsions
• 43˚C (109˚F) – death
Lesion of Posterior Hypothalamus
• Inability to increase body temperature
• Hypothermia in a cold environment
• Confusion followed by loss of thermoregulation at
28˚C (82˚F)
Fever
• Interleukin-1 is endogenous pyrogen
• Released from macrophages
• Acts on neurons and glia in medial preoptic area –
“pyrogenic zone”
• Glial cells produce cytokines and PGE2
• PGE2  cold-sensitive neurons
• PGE2  warm-sensitive neurons
• PGE2 will increase temperature set-point and
thus body temperature will rise - fever
Febrile Conditions
105
104
Actual Body Temperature
Setting the Thermostat
Set-Point
suddenly raised
to high value
Crisis
Body Temperature (°F)
103
102
101
Chills
Vasoconstriction
Piloerection
Epinephrine secretion
Shivering
100
Fever Breaks
Vasodilation
Sweating
99
Set-Point suddenly
reduced to low value
98
1
2
3
Time in Hours
4
5
Feeding Regulation
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Feeding Regulation
Feeding Center
• Lateral hypothalamic nucleus
• Stimulated by low glucose levels
• Initiates feeding
• Amphetamines inhibit food intake by enhancing Norepi and DA
levels in lateral hypothalamic nucleus
Satiety Center
• Ventromedial nucleus
• Stimulated by high glucose levels or CCK
• Inhibits food intake
Feeding Regulation
Leptin
• Protein hormone released by fat cells
• Circulating levels directly proportional to amount of
adipose tissue in body
• Acts on receptors in lateral hypothalamus
• Inhibits affects of neuropeptide Y and
anandamine – both feeding stimulants
• Inhibits feeding
• Genetically altered mice with no leptin or leptin
receptors are obese
Feeding Regulation
Ghrelin
• Hormone that stimulates appetite
• Produced in stomach and upper small intestine in
response to significant weight loss
• May explain why it is difficult to maintain weight
loss after dieting
• Not produced in patients that have undergone gastric
bypass surgery
Feeding Regulation - Lesions
Lesion of feeding center
• Results in loss of desire to eat
• Leads to aphagia and ultimately death
Lesion of satiety center
• Results in compulsive overeating
• Leads to hyperphagia and obesity
Water (Fluid) Regulation
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Fluid Regulation
Thirst Center
• In anterior and lateral hypothalamus
• Closely tied to supraoptic/ADH system
controlling fluid homeostasis
• Stimulation results in fluid consumption polydipsia
Satiety Center
• Ventromedial nucleus
• Tied to food intake
• Food and fluid intake not mutually exclusive
Fluid Regulation - Lesions
Lesion of lateral hypothalamus
• Loss of thirst center
• Results in very little fluid intake - adipsia
Lesion of satiety center
• Results in compulsive overeating/drinking
• Leads to hyperphagia and polydipsia
Sexual Behaviors
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Sexual Behaviors
• Preoptic area regulates release of
gonadotrophic hormones
• Cyclical in females
• Topical with fluctuations in males
• Preoptic area important in male behaviors mounting
• Ventromedial nucleus important in female
behaviors - lordosis
Sexual Orientation
Preoptic area is different in males
and females
• Sexually dimorphic nucleus
• Larger in male rats vs female rats
Sexual Orientation
Human studies
• Simon LeVay
• INAH-3 smaller in homosexual males, size of
heterosexual females
Sexual Orientation
Human studies
• Laura Allen and Roger Gorski
• Area of anterior commissure is normally larger in women
than men
• Anterior commissure 34% larger in homosexual males
than in heterosexual males; 18% larger than those in
heterosexual females
• Dick Swaab
• Suprachiasmatic nucleus larger (twice the number of
cells) in homosexual males than in heterosexual males
Sexual Orientation
Human studies
• Savic et al.
• PET scans of heterosexual subjects smelling
putative human pheromones
• AND (in male sweat), EST (in pregnant female
urine)
• HeW (AND) = preoptic area and DM hypo.
• HeM (EST) = PVN and DM hypothalamus
• HeW (EST) and HeM (AND) = areas that
process common odors, no hypothalamus
Sexual Orientation
Human studies
• Savic et al.
• PET scans of homosexual male and
heterosexual female subjects smelling
putative human pheromones
• HoM (AND) = PVN and DM hypothalamus
• HeW (AND) = PVN and DM hypothalamus
Sexual Orientation
Human studies
• Lindstrom and Savic
• PET scans of lesbian subjects smelling putative
human pheromones
• HoW (AND) = olfactory networks, not hypo.
• HoW (EST) = partly shared responses with
HeM - anterior hypothalamus
Sexual Orientation
Fear and Pleasure
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Fear and Pleasure
Flight response
• Stimulation of lateral anterior hypothalamus
• Sympathetic response
Ventromedial nucleus stimulation
• Defensive response - fear
• Avoidance reaction
Preoptic area stimulation
• Pleasure
Circadian Rhythms
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Circadian Rhythms
Suprachiasmatic nucleus is considered to be
the biological clock
• Endogenous rhythm with 24 hour periodicity
• Rhythm influenced by light
• Retina projects directly to SCN
Sleep and Wakefulness
Preoptic Area
Anterior
•Sympathetic
Responses
•Feeding
Center
•ADH / Oxytocin
•Para. Responses
•Lower Body Temp.
•Sleep / Rhythms
SUPRAOPTIC
ZONE
•Releasing Factors
•Satiety Center
•Avoidance
Reactions / Fear
TUBERAL
ZONE
•Thirst Center
•Symp. Responses
•Raise Body Temp.
•Waking
Posterior
MAMILLARY
ZONE
Medial
Sleep and Wakefulness
• In anterior hypothalamus / preoptic area
• Production of PGD2 promotes sleep
• Lesions result in insomnia
• In posterior hypothalamus
• Production of PGE2 promotes waking
• Lesions result in hypersomnolence
Questions??