Brain and gut interaction and

appetite

Prof Michael Mathai

College of Health and Biomedical
Science
Main structures/components
•  Central nervous system
–  Brain areas implicated
–  Neural signalling
–  Interface with systemic mediators
•  Gut mediators
–  Enteric nervous system
–  Sensory neurons
–  Hormones
•  Influence of the microbiome
 How does the brain signal
appetite?
•  Specialised centres that detect nutrient
levels in the blood
•  Connections between hypothalamic,
medullary and cortical structures
•  Influence of neurohormonal signalling from
the periphery and social/stress signals
from cortical structures
Influences on food appetite
Gut hormones and appetite control
Cholecystokinin - CCK
Brain areas involved in appetite
Connections between brain and peripheral
tissues
 The hypothalamus has several discrete regions
that act in concert in the regulation of food intake
and energy balance
 •  The arcuate nucleus
receives signals from
circulation that influence
appetite sensation, food
intake and energy
expenditure.
•  Major appetite hormones
are released from
systemic tissues e.g.,
adipose tissue, pancreas
and gut.
•  The arcuate nucleus does
not have a blood brain
barrier so circulating
factors can access
receptors on neurones in
this area.
Gut hormones act on vagal afferents to influence
food appetite
Ghrelin influence on appetite
•  Mechanism of action:
–  Secretion increases when stomach is
empty and stops when stomach is full
–  Acts on neurons in hypothalamus
–  Increases hunger, gastric acid section and
GIT motility
 Body Weight

Fat Mass Lean Mass Bone Mass

Adipose Tissue Muscle Tissue

•  Proportions depend on lifestyle and genetics

•  Some fat-derived hormones increase with
obesity and influence health
Adipose tissue as an endocrine organ
 Cytokine activation and
inflammation
•  Release of cytokines activates eicosanoid
biosynthesis

•  IL-1beta, IL-6, TNF-alpha involved in

pro-inflammation

•  IL-4, IL-10, IL-11, IL-13 involved in anti-

inflammation
Functions of Leptin
 Leptin resistance

•  Despite high levels of leptin from

increased adipose tissue, satiety signalling
in the brain and fatty acid oxidation in
muscle do not seem to increase
•  Possible intracellular interference from
increased phosphotyrosine phosphatase
activity
•  Inhibition of this enzyme protects animals
from diet-induce obesity
Leptin resistance and weight gain
 Treating obesity
•  Surgery
•  Dietary restriction
•  Exercise
•  Drug treatments
 Surgical techniques
•  Liposuction
•  Gastric bypass
•  Gastric lap-banding
•  Bilio-pancreatic diversion

•  Advantages and disadvantages

associated with all surgical outcomes
Gastric Roux en Y Bypass
Rapid weight loss can be
sustained for years
Mineral and nutritional
supplements required for life
Residual stomach size 30-50ml
Malabsorption of nutrients,
depending on siz of ileal
remnant
Late regain of weight in 10-20%
after 2-5 years
 Gastric lap-banding

Advantages:
*  Keyhole approach …. Less scarring or wound problems
* Adjustable : by filling port the outlet size can be reduced
*  Reversible: By removing fluid or the band.
*  No malabsorbtion
Disadvantages
*  Easy to cheat ….constant nibbling, chocolates/sweets or high calorie drinks taken
*  Mechanical problems: prolapse, pouch dilation, band erosion,food bolus obstruction,
slippage of the stomach through the band.
*  infection of the band or port leak
* An entree portion forever or pain and vomiting may occur
 How does surgery inhibit appetite?

•  Physical restriction of stomach volume

•  Increased mechanical stretch sensation
•  Afferent signals are transmitted to the
brainstem to induce sensation of fullness
•  Satiety hormones such as CCK and GLP-
1 are released which act on the CNS
Bilio-pancreatic diversion

Removal of gall bladder

Resection of stomach
residual size 250-300ml
Stomach can stretch over
time
Malabsorption of nutrients
 Dietary restriction
•  Very Low Calorie Diet (less than 0.8MJ/day
•  Low carbohydrate (fuel switching, rapid initial)
•  Low fat, High protein
•  High bulk
•  Nutrient mix
•  Side-effects eg. Loss of lean mass, key nutrients
•  Yo-yo effect of weight loss and rebound weight
gain. Success rate after 5 years very low (>10%)
 Altering Nutrient Mix
•  Increasing protein:carbohydrate ratio
reduction in insulin
•  Increasing level of omega-3 fatty acids
decrease in plasma triglycerides
improved glucose tolerance
 Exercise
•  Non-weight bearing eg. Aqua aerobics, cycling,
swimming
•  Stimulates appetite
•  Discipline required
•  Best in combination with dietary strategy
•  Prone to rebound weight gain
 Drug treatments
•  Xenical/orlistat pancreatic lipase inhibitor
•  Sibutramine appetite suppressant
•  Fenfluramine and phentermine (discontinued)
•  Acomplia/Rimonabant
•  Caffeine/bitter orange/chromium
Bacteria and gut
Bacteria help metabolise and consume ingested food
Interaction of gut bacteria with intestinal health and
appetite signalling
Gut bacterial signals and host appetite signalling
 Summary

•  The brain and gut communicate via neural and hormonal

signals in the regulation of appetite.
•  The vagus nerve is important for neural signalling
•  Major gut hormones discussed are ghrelin, CCK, insulin
while there are many others
•  Adipose tissue also release hormones that influence
appetite eg. leptin and other cytokines
•  Higher brain centres can influence appetite, via eg.
stress or social behaviour pathways
•  The gut microbiome can act by altering the release of
cytokines that influence vagal afferent signalling