Post on 26-May-2020
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Research seminar (August 6, 2019)
Feeding regulatory mechanism
in the brain of chicks
Tetsuya Tachibana (Ehime University)
Chicken (Gallus domestics) © ウィキペディア
© wikipedia
Chicken is the most numerous domestic animal (vertebrate)
in the world.
Chicken is produced from the red junglefowl.
They were originally used for cockfighting or pet, but are
now mainly used for egg and meat production for human
food.
Breed Use Egg/ year Adult BW (kg)
Male Female
White Leghorn Eggs 280 2.5 2
Barred Plymouth Rock Meat & Eggs 200 4.0 3.0
White Cornish Meat 100 5.5 4.0
Production capacity of representative chicken breed.
Body weight (g)
Broilers consume more diet
1000
600
200
0
7 1 14 21
Age (day)
800
400
80
60
40
20
0
7 1 14 21
Food intake (g)
Age (day)
Layer Broiler RJF
Breeding of broiler © Dr. Panl Aho, Poultry USA, 2002
Year Age of shipping BW of shipping FCR Mortality
1925 112 days 1.00 kg 4.7 18%
1935 98 1.18 4.4 14
1945 84 1.40 4.0 10
1955 70 1.50 3.0 7
1965 63 1.59 2.4 6
1975 56 1.68 2.1 5
1985 49 1.90 2.0 5
1995 45 2.09 1.9 5
2005 45 2.45 1.9 5
Productivity of broiler was improved drastically in these 100 years.
Problem of broiler
Genetic selection for rapid growth produced current broilers.
However, the rapid growth put a heavy burden on their bodies.
Problem in legs
The body weight increases rapidly but the growth of their legs
is not so fast.
Ascites
The rapid growth put strain on the heart.
Because of malfunction of the right ventricle by pulmonary
arterial hypertension, hepatic-veins pressure rises and then
humors leak at an abdomen.
Heat stress
The rapid growth requires active metabolism and thereby
causes the increase in body temperature.
They eat even though their body temperature increases
Diet restriction decreases the heat accident
They eat even though their metabolism is abnormal
Their ascites is suppressed by feed restriction
They eat even though their laying is suppressed
Feed restriction improves laying in broiler
What is the cause of problem?
Where is the problem in feeding regulation of broiler?
Which is important for feeding regulation in chickens?
Broilers can not control their food intake!
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Contents of this seminar
Factors regarding feeding regulation Feeding regulation in the brain Feeding regulation in chicks
Why animals eat?
Animal is heterotrophs, so can not fix carbon for energy source.
Animal must eat food to obtain organic carbon in the form of
carbohydrates, fat and proteins.
To obtain water
・Carbohydrates
・Lipids
・Proteins
To obtain satisfaction
・Satiety
・Fulfill five senses
・etc
To obtain essential nutrients
To obtain materials for body
・Essential amino acids
・Vitamins
・Minerals
・etc
To obtain energy source
Animals consume energy
Exercise Digestion Absorption
・Movement
・Work
・Exercise
・Ingestion
・Digestion
・Absorption
・Sweating
・Pilomotor
Life sustaining (Basal metabolism)
・Respiration
・Beating
・etc Energy consumption (Japanese 20s)
Male: about 2500 kcal/ day, Female: about 2000 kcal/ day
Regulation of body temperature
70%
10%
20%
Inte
rnal energ
y
Sufficient Reduction
Insufficient Adequate Excess
Body weight loss Body weight gain
Growth
Production
Eating
Energy requirement
We eat to obtain energy
Starvation
Obesity
0
20
40
60
80
100
120
92 93 94 95 96 97 98 99 00 01 02 03 04 05
Starvation and death Population of Japan (2008): 127,288,419
© 厚生労働省
(n) Death from starvation in Japan
(45 person died by starvation in 2011)
Year
24 26 28
61
87 74
82 86 90
64 73
97
71 82
About 795 million people in the world do not have enough food to
lead a healthy active life (about one in nine people on earth).
Obesity and disease
In 2014, about 641 million adults, 18 years and older in the
world were obese (BMI > 30).
Ischemic heart disease
Menstrual disorder Hyperlipidemia
Hypertension
Cerebral stroke
Fatty liver Liver cirrhosis
Kidney disease
Sleep apnea syndrome
Back pain Knee pain
Diabetes
World's obese population hits 640 million, according
to largest ever study (Imperial College London,
March 31, 2016)
・Neuropathy
・Nephropathy
・Retinopathy
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Use of energy source in the body
Glucose Amino acid Fatty acid Ketone
Brain
Heart
Liver
Skeletal muscle
Erythrocyte
Blood glucose should be maintained (hunger: 80~100mg/100ml)
Useful Use in specific case Not available
150
100
50
0 eating
07 22 08 09 10 11 12 13 14 15 16 17 18 19 20 21
Time
At hunger
80~100 mg/dl
At 2 h after eating
~150 mg/dl
mg/d
l
Change in blood glucose
If blood glucose is remarkably decreased…
Glucose shortage in brain: dizziness, tiredness, unconsciousness
Eating diet increases blood glucose.
Information of blood glucose
is sent to the brain
Digestive tract in human
Stomach
Jejunum
Anus
Cecum
Appendix
Rectum
Colon
Large intestine
Pancreas
Liver
Gallbladder
Duodenum
Esophagus
Small intestine
Ileum
Ascending
Cardia
Sigmoid
Fundus Body
Pylorus
Transverse
Descending
Functions of stomach
Organ Time
Esophagus 1-60 sec
Stomach 4 hr
Small intestine 9 hr
Large intestine 12-24 hr
Approximate transit time of
food from digestive tract proteinase: pepsin
Digestion of protein
Sterilization of food hydrochloric acid
Pooling of food About 4 hr
Ingesta alters stomach volume
at huger: 50 ml
at satiety: 1500-2000 ml
Information of stomach expansion is sent to the brain via afferent vagus nerve
Diet Stomach Small Intestine
Digestion of protein
Storage of diet
Digestion of carbohydrate
Absorption of glucose
Stomach volume
Brain
Blood glucose
Vagus nerve Blood
Satiety
- We can satiate with water
- Vagotomy does not affect
feeding
- The fast eating causes the overeating
Satiety model
Hunger
Stimuli of Diet
+ Memory of food
Sound Smell Vision Taste Touch
Brain
Need not necessary Relaxation of stomach
Decrease of blood glucose
Hunger model
Blood glucose does not decrease
when we are hungry
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Internal factors
Age Sex Metabolism
Genotype Stress status
Health status Reproductive status
Low or high temperature
Temperature fluctuation
Humidity
Novel environment
Environmental factors
Digestibility Energy
Nutrients Shape
Taste Flavor
Water Palatability
Dietary factors
Feeding Behavior
Factors regarding feeding regulation
Brain
Expansion of stomach
Blood glucose
Start eating
Feeding center
Apastia and starvation
3rd ventricle
Stop eating
Satiety center
Bulimia and obesity
Feeding and satiety centers
Lateral area Lateral area
Ventromedial area
Dorsomedial area
PVN DMN
LHA VMN
ARC
Stimulation LHA Lateral hypothalamic area
Inhibition VMN Ventromedial nucleus
DMN Dorsomedial nucleus
Both ARC Arcuate nucleus
PVN Paraventricular nucleus
rostral
caudal
Hypothalamus is important for feeding
3rd ventricle
Neuron and nucleus
100 nm
Nerve nucleus
Synapse
Nerve fiber
Nucleus
Dendrite
Axon
Neuron
Neurotransmitter (when activated)
Nerve cell body Population of nerve cell body
Glucose and hypothalamic neurons
Active Inactive
Inhibited by glucose
Glucose-sensitive neuron
Activated by glucose
Glucose-receptive neuron
Inactive Active
With glucose With glucose
3rd ventricle
Lateral area Lateral area
Ventromedial area
Median eminence
Blood
Glucose and hypothalamus
Feeding center
Satiety center
Inhibited by glucose
Glucose-sensitive neuron
Activated by glucose
Glucose-receptive neuron
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Decrease in
blood glucose
Increase in blood glucose
Glucose-sensitive neuron Acitivate Inhibit
Glucose-receptive neuron Inhibit Activate
Feeding center (start eating)
Satiety center (stop eating)
Before eating During eating
Start eating Stop eating
Glucose and feeding regulation History of research regarding feeding
Year Researcher Findings or hypothesis
1900 Sherrington “Hunger is occurred in cerebral cortex”
1912 Cannon “Stomach contraction theory”
1942 Hetherington, Ranson Satiety center
1951 Anand, Brobeck Feeding center
1951 Kennedy “Lipostatic theory”
1952 Mayer “Glucostatic theory”
1964 Brobeck Glucose sensitive and receptive neurons
1970 Monoamine theory: neuropeptide theory
1994 Zhang Leptin
Amino acid
Glutamic acid
Glycine
Asparagic acid
Taurine
GABA
Amine
Dopamine
Noradrenaline
Adrenaline
Serotonin
Histamine
Gass
Nitric oxide
Carbon oxide
Adenosine
Adenosine
ATP
Choline
Acetylcholine
Peptide (continue)
Neurotensin
CGRP
Bombesin
Cholecystokinin
Vasopressin
Oxitocin
Endothelin
Glucagon
Angiotensin
Galanin
POMC
CRH
GLP-1
Peptide
Somatostatin
Growth hormone
Tachykinin
TRH
Enkephalin
Neuropeptide Y
Neurotransmitters
Stimulation
Orexigenic
NPY Neuropeptide Y
AGRP Agout-related protein
MCH Melanin-concentrating hormone
ORX Orexin
Inhibition
Anorexigenic
MSH Alpha-melanocyte-stimulating hormone
CART Cocain and amphetamine regulated transcript
CCK Cholecystokinin
CRH Corticotropin-releasing hormone
Feeding regulatory peptides
There are a lot of feeding regulatory peptides in the
hypothalamus of mammals.
PVN DMN
LHA
VMN
ARC
Median Eminence
CRH
CCK
MSH/CART
NPY/AGRP
MCH
ORX
Distribution of peptides
Glucose receptive
Glucose sensitive
Anorexigenic peptides CRH CCK MSH CART
Orexigenic peptides ORX MCH NPY AGRP
Feeding
Energy expenditure
Adipose tissue
Reduction of adipose tissue
Lipostatic theory Keep body fat constantly
Lipostatic theory
Leptin
Leptin
Feeding
Energy expenditure
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PVN
DMN
LHA
VMH
ARC
Stomach Median Eminence
Stimulation of Feeding
Hypothalamic orexigenic system
NPY/AGRP
MCH
ORX
Ghrelin
CRH
CCK
Glucose sensitive
Suppress anorexigenic effects
PVN
DMN
LHA
VMH
ARC
Adipose Tissue Median Eminence
Inhibition of Feeding
Hypothalamic anorexigenic system
CRH CCK
MSH/CART
Leptin
Glucose receptive
PVN
DMN
LHA
VMH
ARC
Adipose Tissue Median Eminence
Inhibition of Feeding Stimulation of Feeding
Model of hypothalamic regulation
NPY/AGRP
MCH
ORX
Ghrelin
CRH CCK
MSH/CART
Leptin
Stomach
Intracerebroventricular injection
We performed intracerebroventricular (ICV) injection technique
based on Davis et al. (1979).
This technique can inject without stress and finish the injection
within 1 min.
ICV injection device Fixation of chick head
The device is made with acrylic plate. A hole is opened in the top plate.
The head is inserted into the device and fixed. The hole is located immediately above the left lateral ventricle.
Neuropeptides Mammal Chick
Amylin ▼ ▼
Arg-vasopressin (Arg-vasotocin) ▼ ▼
Bombesin ▼ ▼
Calcitonin-related peptide ▼ ▼
Cocaine and amphetamine regulated transcript ▼ ▼
Cholecystokinin ▼ ▼
Coricotropin-releasing hormone ▼ ▼
Gastrin ▼ ▼
Gastrin-releasing peptide ▼ ▼
Glucagon ▼ ▼
Glucagon-like peptide-1 ▼ ▼
Feeding-inhibitory peptide #1 ▲ Increase ▼ Decrease - No change
Neuropeptides Mammal Chick
Glucagon-like peptide-2 ▼ ▼
Insulin ▼ ▼
α-melanocyte-stimulating hormone ▼ ▼
β-melanocyte-stimulating hormone ▼ ▼
Neuromedin B ▼ ▼
Neuromedin C ▼ ▼
Neuromedin S ▼ ▼
Neuromedin U ▼ ▼
Neuropeptide FF ▼ ▼
Neuropeptide K ▼ ▼
Neuropeptide S ▼ ▼
Feeding-inhibitory peptide #2 ▲ Increase ▼ Decrease - No change
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Neuropeptides Mammal Chick
Oxyntomodulin ▼ ▼
Oxytocin ▼ ▼
Pituitary-adenylatecyclase-activating polypeptide ▼ ▼
Prolactin-releasing peptide ▼ ▲
Stresscopin ▼ ▼
Substance P ▼ ▼
Thyrotropin-releasing hormone ▼ -
Urocortin ▼ ▼
Vasoactive intestinal peptide ▼ ▼
Xenin ▼ ▼
Feeding-inhibitory peptide #3 ▲ Increase ▼ Decrease - No change
Neuropeptides Mammal Chick
Agout-related peptide ▲ ▲ -
β-endorphin ▲ ▲
Endomorphin-2 ▲ ▲
Galanin ▲ ▲
Ghrelin ▲ ▼
Growth hormone-releasing hormone ▲ ▼
Melanin-concentrating hormone ▲ -
Motilin ▲ -
Neuropeptide Y ▲ ▲
Orexin ▲ -
Somatostatin ▲ ▼ ▲
Feeding-stimulatory peptide ▲ Increase ▼ Decrease - No change
PVN
DMN
LHA
VMH
ARC
Adipose Tissue Median Eminence
Inhibition of Feeding Stimulation of Feeding
Model of hypothalamic regulation
NPY/AGRP
MCH
ORX
Ghrelin
CRH CCK
MSH/CART
Leptin
Stomach
This model is not useful for feeding regulatory
mechanism in the brain of chicks.
Feeding-regulatory
peptides
Mammalian
peptide
Peptides which show
same effect in chicks
Inhibitory peptide 32 30
Stimulatory peptide 10 5
Comparison between vertebrates
The number of stimulatory peptide is less than inhibitory peptide
Central feeding regulatory mechanism in chicks is different from
mammals? (Sugimoto)
There may be unknown factor (Aihara and Masunari)
July, 2012
Chickens are different from mammals
・Oviparity: chicks can eat after hatching.
・They do not have teeth.
・Their digestive tract is different from mammals.
We are investigating how chicks control their feeding behavior.
Crop Esophagus
Gizzard
Ileum
Cloaca
Colon
Cecum Duodenum
Jejunum
Yolk sac
Liver
Proventriculus