CENTRAL CONTROLS OF FOOD INTAKE AND APPETITE - PowerPoint Presentation

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CENTRAL CONTROLS OF FOOD INTAKE AND APPETITEPart-I

Dr Pramod Kumar

Asstt

. Professor

Department of Veterinary Physiology

Bihar Veterinary College, Patna

CENTRAL CONTROLS OF FOOD INTAKE AND APPETITE Coordination by the Hypothalamus

Role of the Brainstem

Neuropeptides

Central Neurotransmitters

Hedonic Mechanisms

Mnemonic Representations of Experience with Food

Endocannabinoids

Coordination by the Hypothalamus Hypothalamus - “gate keeper” in the control of food intake and appetite.



Peripheral signals of energy balance may act directly on the hypothalamus to control food intake



communication between the hypothalamus and higher cortical centers pertaining to food memory and rewarding aspects of food



lateral hypothalamus “hunger center,”



medial hypothalamus “satiety center”.

Role of the Brainstem 

sensing of energy balance and modulation of food intake



dorsal

vagal

complex (DVC) is the main organ responsible for facilitating the communication between peripheral signals of food intake and hypothalamic nuclei



DVC consists of : nucleus of the

tractus

solitarius

(NTS), area

postrema

(AP) and dorsal

vagal

nucleus (DVN).

Vagal nerve afferents: carry sensory information relaying hunger and satiety from the gut directly to the NTS (increased meal size and duration)



AP receive metabolic signals of energy balance (e.g., hormones and nutrients carried by the blood) directly (absence of complete BBB)



Efferent pathways : hypothalamus ↓→ DVN (modulates) ↓→ efferent



vagal

nerve activity → alter gastric emptying, gastric motility and pancreatic secretions.

Hypothalamic Nuclei Implicated in the Control of Food Intake  Arcuate

nucleus (ARC) is the main hypothalamic area which controls food intake and neurons within the ARC:



1- neurons contains

neuropeptide

Y (NPY) and Agouti related peptide (

AgRP

) activates to enhance food intake (

orexigenic

)



2- neurons containing pro-

opiomelanocortin

(POMC) and cocaine and amphetamine regulated transcript (CART) and activates to reduce food intake (

anorexigenic

)

Axons from ARC (NPY/AgRP and POMC/CART) neurons project to other areas of the hypothalamus:



Paraventricular

nucleus (PVN) causes

hyperphagia

and obesity in rats



Ventromedial

nucleus (VMN),

dorsomedial

nucleus (DMN), lateral hypothalamic area (LHA) and

perifornical

area (PFA) modulates food intake

Hormones of GI tract

Neuropeptide

Y is the most powerful central stimulant of appetite and approx. 90% of NPY neurons co-express

AgRP



Central administration of NPY enhances food intake



repeated daily injections of NPY into the hypothalamus result in chronic

hyperphagia

and weight gain in these animals



Ablation of NPY/

AgRP

neuron leads to reduce body weight via reduced food intake



Y1 and Y5 receptors seem to mediate the

orexigenic

effect of NPY

Agouti-Related Peptide/AgRP



competitive antagonist of

anorexigenic

central

melanocortin

receptors in the PVN and increases food intake



action on

orexin

or

opioid

receptors

Pro-

opiomelanocortin

and

Melanocortins

(POMC)



precursor of α

melanocyte

-stimulating hormone.



αMSH

binding to the MC4R acts to reduce food intake



homozygous mutations in the POMC gene in humans result in early- onset obesity



Cocaine and Amphetamine Regulated Transcript is co-expressed by most POMC neurons in the ARC.



Central

intracerebroventricular

administration of CART reduces food intake

Hypothalamic Releasing Hormones

Corticotropin

-releasing hormone and

thyrotropin

releasing hormone are expressed in PVN neurons.



both inhibit food intake



Orexins



Orexin

A and B activate G-protein coupled receptors to increase food intake.

Melanin-Concentrating Hormone is an

orexigenic

signal expressed in neurons located in the LHA



Infusion of MCH increases food intake and body weight



Brain-Derived

Neurotrophic

Factor is highly expressed in the VMN and acts via MC4R signaling to reduce food intake

Serotonin produced in the dorsal raphe nucleus  reduces food intake and body weight

Norepinephrine

produced in the DVC and locus

coeruleus

, has differing effects on α

2

receptors stimulates food intake, α

1

, β

2

, and β

3

receptors reduces food intake

Dopamine inhibit food intake in the ARC and LHA have

orexigenic

action in the VMN to act on D1 and D2 receptors of dopamine which reduces food intake.

Hedonic mechanisms and cortico-limbic pathways control appetite and food intake -



Visual, smell and taste signals can override satiety signals to maintain food intake



These sensory signals are conveyed from NTS in the brainstem to

cortico

-limbic reward centers implicated in appetite regulation



Dopamine, serotonin,

opioids

and nor-epinephrine have been implicated as important neurotransmitters involved in signaling within this network.

Mnemonic representations of experience with food –



Past experience with specific foods forms an important contributor to continue consumption



Orbito

-frontal cortex (OFC), an area that receives converging sensory input in the non-homeostatic control of food intake.

Endocannabinoids shown to produce a dose dependent orexigenic effect and this effect is thought to occur via modulation of reward circuitry

1)

Anandamide

derived from membranous phospholipids

2)

Arachidonoylglycerol

(2-AG), derived from triglycerides



Endocannabinoids

may also act directly on the hypothalamus to exert their

orexigenic

effect.



These substances are secreted by postsynaptic neurons and act in retrograde fashion.