1

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!

2

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

3

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

4

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

5

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

6

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

7

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