What controls our appetite or suppresses it? How can we use this knowledge to eat better?

1. DIET AND NUTRITION
Appetite Regulation
By
Dr Madhumita Sen

2. Learning Objectives
In this lesson the student will learn
 What is appetite
 Brain control of appetite
 Hormones that regulate appetite, and
their basic modes of action.

3. Appetite
 Appetite is the desire to eat food, felt as hunger.
 Appetite exists in all higher life-forms, and serves
to regulate adequate energy intake to
maintain metabolic needs.
 It is regulated by a close interplay between
the digestive tract, adipose tissue and the brain.

4.  Appetite is different from hunger.
 Hunger is our physical need to eat.
 You can want to eat but not need to eat (for
example, wanting to eat dessert after a big meal).
 Or you can need to eat but not want to eat (for
example, losing your interest in food when you’re
stressed).
 When we lose stored fat, our body mounts a major
response to conserve energy and boost appetite,
defying further weight loss and encouraging
regain.
 Note: Prader-Willi Syndrome and Hypothalamus.

5.  When stressed, appetite levels may increase and
result in an increase of food intake.
 Decreased desire to eat is termed anorexia,
 Increased appetite is called orexia
 While polyphagia (or "hyperphagia") is increased
eating.
 Dysregulation of appetite contributes to
 anorexia nervosa,
 bulimia nervosa,
 cachexia,
 overeating, and
 binge eating disorder.

6.  The hypothalamus, a part of the brain, is the main
regulatory organ for the human appetite.
 The neurons that regulate appetite appear to be
mainly serotonergic.
 The hypothalamus senses external stimuli mainly
through a number of hormones such as leptin,
ghrelin, PYY 3-36, orexin and cholecystokinin; all
modify the hypothalamic response.
 They are produced by the digestive tract and
by adipose tissue (leptin and adiponectin).

7.  Systemic inflammatory mediators, such as tumor
necrosis factor-alpha (TNFα), interleukins 1 and 6
and corticotropin-releasing hormone (CRH)
influence appetite negatively; this mechanism
explains why ill people often eat less.
 In addition, the biological clock (which is regulated
by the hypothalamus) stimulates hunger.
 Processes from other cerebral loci, such as from
the limbic system and the cerebral cortex, project
on the hypothalamus and modify appetite.
 This explains why in clinical depression and stress,
energy intake can change quite drastically.

8.  Appetite is regulated by a complex system of
central and peripheral signals which interact in
order to modulate the individual response to
nutrient ingestion.
 Peripheral regulation includes
1. satiety signals and
2. adiposity signals, while
 Central control is accomplished by several
effectors, including the
1. neuropeptidergic,
2. monoaminergic and
3. endocannabinoid systems.

10. Hormones in Appetite Regulation
Calcitonin Released in response to gastrin and
changes in serum calcium levels
Secreted by cells in the thyroid, GI
tract, and pancreas
A complementary signal responsible for
fine tuning the eating process

11. Amylin A partner hormone to insulin, released
after meals
Secreted by the pancreas
It slows the emptying of our stomach
and suppresses glucagon (glucagon
raises blood sugar)

12. GLP-1 Released when blood glucose levels are
above the norm
Secreted by cells of the gut in proportion
to the amount of energy ingested
Stimulates insulin and amylin secretion,
may assist in signalling the brain to stop
eating

13. Leptin Released with low calorie intake and low
body fat levels. Secreted by fat cells
Low leptin means a slower metabolism and
drive to increase food consumption.
Administering leptin analogs in humans is
ineffective for appetite suppression.
Leptin exists to prevent starvation, not to
lose weight. Only when leptin is provided
along with amylin, slight fat loss may occur

14. Gastrin Released when food enters stomach,
protein dense foods are the most potent
stimulator of gastrin
Secreted by cells in
stomach/small intestine
Initiates the digestion process

15. Secretin Released when acids reach small intestine
Secreted by cells in small intestine
Produces pancreatic fluid, inhibits gastrin
release, and enhances effects of
cholescystokinin

16. Cholecysto
kinin
(CCK)
Released when protein and fat enter the
small intestine
Secreted by cells in small intestine
Signals pancreas to produce enzymes,
inhibits gastrin, stimulates gallbladder
contraction, and triggers satiety in the
brain

17. Gastric
inhibitory
polypeptide
(GIP)
Released when food enters small intestine
Secreted by cells in small intestine
Enhances insulin release, inhibits gastric
secretions and motility
Motilin Released when bicarbonate is dumped into the
small intestine and between meals/when
fasting
Secreted by cells in small intestine
Promotes muscle contraction of GI tract, and
when released between meals, you’ll notice
borborygmus (growling stomach)

18. Somato-
statin
Released between meals to reduce digestive
activity
Secreted by stomach, intestine and pancreas
Slows gastric emptying, reduces GI muscle
contractions and blood flow to gut
PYY 3-
36
Released in the hours following a meal,
presumably to suppress appetite
Secreted by the small/large intestine
Inhibits stomach motility while increasing water
and electrolyte absorption in the colon. May also
suppress pancreatic enzyme secretion. Obesity
seems to be a PYY 3-36 deficient state

19. Ghrelin Released in response to low food
intake/fasting
Secreted by cells of the stomach,
pancreas, placenta, kidney, pituitary and
hypothalamus
Stimulates release of growth hormone to
encourage eating and acts to regulate
energy balance.

21.  Adiponectin
 Adiponectin, also called adipocyte complement-
related protein is a 244-amino acid protein secreted
from adipose tissue.
 The plasma concentration of adiponectin is
inversely correlated with adiposity in humans.
 Studies show that treatment with adiponectin can
reduce body weight gain, increase insulin sensitivity,
and decrease lipid levels.
 Thus adiponectin, as well as increasing energy
expenditure, may also provide protection against
insulin resistance and atherogenesis.

22.  Resistin
 Resistin is also produced by adipose tissue and
appears to increase insulin resistance.
 Circulating resistin is increased in obese people
and falls after weight loss.
 Although resistin may contribute to the
development of insulin resistance and diabetes in
obesity, its role in the pathogenesis of obesity
remains to be defined.

23.  Pancreatic Hormones
 Insulin
 The pancreatic hormone insulin was one of the first
adiposity signals to be described and, like leptin, is
positively correlated with long-term energy
balance.
 Plasma insulin concentrations depend on peripheral
insulin sensitivity, with visceral fat being a key
determinant.
 However, unlike leptin levels, which are relatively
insensitive to acute food intake, insulin secretion
increases rapidly after a meal. Insulin is an anabolic
hormone and increases appetite.

24.  Pancreatic polypeptide
 Pancreatic polypeptide (PP) is a member of the
PP-fold family of peptides which also includes
peptide YY (PYY) and NPY
 PP is primarily produced by cells at the periphery
of the islets of Langerhans but is also secreted by
the exocrine pancreas and distal gastrointestinal
tract.
 Plasma PP concentrations show diurnal variation,
with lowest levels in the early hours of the morning
and highest in the evening.
 PP directly reduces appetite via the brain.

25.  Oxyntomodulin
 OXM is released in proportion to calorie intake from
the L cells of the small intestine.
 Both central and peripheral OXM acutely reduce
food intake.
 The actions of both GLP-1 and OXM on food intake
may be mediated by the GLP-1 receptor.
 OXM may also reduce appetite by inhibition of
ghrelin release.

26. Central Regulators of Appetite
 Hypothalamic Neuronal Pathways Regulating
Appetite:
 Despite wide daily variation in food intake and
energy expenditure, for most individuals, body
weight remains remarkably stable over long
periods of time.
 For this, food intake and energy expenditure must
be constantly modulated and balanced.
 The hypothalamus is essential for the regulation of
appetite and energy balance.

27.  The brain initiates responses to feeding even
before the ingestion of food.
 The very sight and smell of food stimulates
exocrine and endocrine secretions in the gut as
well as increasing gut motility.
 Ingestion of food stimulates mechanoreceptors
leading to distension and propulsion to
accommodate the food.
 As the food is propelled through the gut regions of
the intestines secrete various hormones that
circulate to the brain and impact hypothalamic
responses

28.  Neuronal circuits within these regions of the
hypothalamus signal using specific neuropeptides,
for example,
 corticotrophin-releasing hormone (CRH/POMC),
 thyrotropin-releasing hormone (TRH),
 neuropeptide Y (NPY),
 brain-derived neurotrophic factor (BDNF),
 orexin, and
 melanin-concentrating hormone (MCH).
 Cocaine and amphetamine regulated transcript
(CART)

30. Orexigenic Pathways
 Neuropeptide Y, NPY
 NPY is expressed throughout the brain with highest
levels found in the hypothalamus.
 NPY is one of the most potent orexigenic factors
produced by the human body.
 Neurons that co-express NPY and agouti-related
peptide (AgRP) stimulate food intake.

31.  Agouti-related peptide, AgRP
 AgRP is a protein, a member of the central
melanocortin system, which in addition to AgRP,
includes αlpha-melanocyte stimulating hormone
(α-MSH).
 AgRP and NPY have evolved to ensure the
signalling of hunger during food scarcity and to
enable the body to endure long periods of
negative energy balance.
 It increases appetite.

32.  Melanin-Concentrating Hormone, MCH
 MCH is an important orexigenic (appetite
stimulating) hormone.
 In addition to modulation of feeding behaviors
and energy expenditure, the MCH system has
been shown to be involved in affective disorders
such as anxiety and depression.
 MCH system is important in the modulation of
stress responses.

33.  The Orexins (A and B)
 The orexins are also called the hypocretins.
 They are shown to increase food consumption
 In addition to increased feeding behavior, central
administration of orexins increases wakefulness
and suppresses REM sleep.
 These latter observations demonstrate that orexins
play a causative role in the regulation of sleep-
wake cycles.

34.  Galanin, GAL
 GAL is expressed in the gut and the brain with wide
distribution throughout the hypothalamus
 It is involved in learning and memory, mood
disorders and anxiety.
 The primary function of GAL is to restore
carbohydrate balance, through behavioral and
metabolic actions by increasing the hunger for
sweet foods.

35.  Endocannabinoids
 The appetite-stimulating effects of marijuana
(Cannabis sativa) have been known for a long
time.
 Several studies have indicated that administration
of cannabinoids stimulates food intake in animal
models.
 Appetite is increased by both peripheral and
central administration of anandamide, one of the
major endocannabinoids.

37. The Anorectic Pathways
 POMC-Derived Melanocortins
 The POMC-derived melanocortin peptides include
α-MSH, β-MSH, γ-MSH and ACTH.
 The melanocortin system has been shown to be
critical in the regulation of food intake and energy
expenditure.
 The melanocortins, α-MSH, β-MSH, and ACTH
directly inhibit the intake of food.

38.  Cocaine- and Amphetamine-Regulated
Transcript, CART
 The cocaine- and amphetamine-regulated
transcript (CART) peptides are neuroendocrine
peptides involved in feeding behavior, drug
reward systems, stress, cardiovascular functions,
and bone remodeling.
 CART peptides are anorexigenic (decrease
appetite)

39.  Galanin-like peptide, GALP
 GALP has anorexigenic effect directly on the
hypothalamus (opposite of Galanin).
 It also increases its responsiveness to the effects of
leptin.
 Apart from inhibition of feeding responses, GALP
also leads to an increase in energy expenditure
and fat oxidation in brown adipose tissue resulting
in a hyperthermic effect.

40.  Corticotropin-releasing factor (CRF) and related
peptides
 CRF results in suppression of spontaneous feeding
responses demonstrating its anorexigenic
properties.
 High serum cortisone has a negative feedback on
CRF, leading to obesity.
 The role of CRF as an anorexigenic hormone may
involve the NPY, melanocortin and CART
systems, acting in a downstream fashion.

41. Hypothalamic Lipid Metabolism and
Energy Homeostasis
 Within the central nervous system the metabolism
of fatty acids is primarily for the purposes of
membrane function and the central regulation of
energy metabolism.
 Fats do not serve as a major source of energy
within the brain.
 Fatty acids, specifically long-chain fatty acids via
the formation of long-chain fatty acyl-CoAs, have
very recently been shown to exert anorexigenic
effects via the hypothalamus.

42.  Serotonin
 Serotonin (5-HT) is a short-acting widespread
neurotransmitter which acts on a number of
receptor subtypes found at high density in the
limbic system as well as in the hypothalamus.
 5-HT stimulates noradrenaline release and modifies
behaviour and mood.
 5-HT shows the most consistent inhibition of food
intake. Serotonin may directly influence the
melanocortin pathway.

43.  Others
 The dopaminergic system is also integral to reward-
induced feeding behavior.
 Other systems, including those mediated by
serotonin, may also be able to modulate both
reward circuitry and homeostatic mechanisms
controlling feeding.
 The noradrenergic system also plays a role in
appetite regulation, with activation of α1- and β2-
adrenergic receptors inhibiting food intake.

44.  Zinc:
 Leptin levels decrease in response to zinc
depletion and increases after zinc
supplementation.
 Importantly, the magnitude of leptin level
changes were proportional to the changes of
cellular zinc.
 Zinc increases TNFa and IL-2 cytokine production.
 Adequate zinc levels reduce appetite, possibly
by increasing brain sensitivity to leptin.

45.  Probiotics:
 Recently, a potential link between gut microbiota
and obesity has emerged.
 The study by Cani et al. [2011] evaluated the
effect of prebiotics on plasma levels of gut
hormones in healthy subjects.
 After two weeks of prebiotic treatment, they
observed increased gut microbiota fermentation,
decreased appetite, and improved postprandial
glucose responses.
 Furthermore plasma levels of GLP-1 and PYY were
increased in subjects following prebiotic treatment.

46.  Estrogen deficiency might result in a higher energy
intake and increased body weight. Food intake
varies across the menstrual cycle. Women tend to
eat more in the luteal phase (the premenstrual
period) compared with the follicular phase.
 Testosterone (directly) seems to have little effect
on food intake, although many people
supplementing anabolic doses of testosterone
(e.g. bodybuilders) do report increased appetite.
 Including a balanced intake of omega-6:omega-3
fats can help with appetite regulation.
 A high protein diet can reduce appetite.

47.  Fibre seem to help control appetite.
 Refined carbohydrates, on the other hand, appear
to increase appetite.
 Dietary fat has mixed results; when combined with
refined carbohydrate it seems to increase
appetite while on its own or combined with
protein, it typically decreases appetite.
 Elderly people have less appetite than young
people from not only decreased energy
expenditure but also from mechanisms potentially
involving sex–steroid balance as well as altered
CNS signalling to and from peripheral organs.

48.  It’s now recognized that overfat individuals have
lower blood concentrations of vitamins and
minerals, especially Zinc, compared to leaner
individuals.
 This may lead to a greater appetite and changes
in fat deposition.

49. Appetite regulation has so
many factors!!!!
Lets revise…..

51. Weight Control
with Herbs and
Oils

52. Phytochemicals and Weight
Control
 Phytochemicals are found in food items and
herbal preparations where they could alter
appetite beyond the effects expected by normal
nutrient loads.
 This added to the fact that they can exert far
fewer side effects, may provide an alternative
treatment or could be used to enhance the effect
of prescription medications.

53. Phytochemicals that Decrease Body Weight
through a Peripheral Mechanism
 Korean Pine Nut Oil
 Korean pine nut oil (P. koraiensis) contains
triglycerides (TG) and more than 92% poly- and
mono-unsaturated fatty acids (PUFAs and MUFAs)
like pinolenic acid, linoleic acid and oleic acid.
 Korean pine nut free fatty acids significantly
increase the release of satiety hormones such as
cholecystokinin (CCK) and GLP 1.
 The appetite sensation "prospective food intake"
and ―desire to eat‖ are also lowered, and these
effects last up to 4 hours.

54.  Palm Oil + Oat Oil Fractions
 Olibra is a fat emulsion formulated from palm oil
(40%) and oat oil fractions (2.5%).
 Its mechanism of action is similar to that of Korean
pine nut oil, increasing and prolonging the release
of peptide YY, CCK and GLP-1 which inhibit upper
gut motility, generating an indirect satiety effect.
 Double-blind, placebo-controlled reports indicate
that Olibra administration to lean, overweight and
obese individuals significantly reduced hunger and
desire to eat with a consequent decrease of
energy and macronutrient intake up to 36 hours
post-consumption.

55.  Garcinia Cambogia (Gambooge)
 G. cambogia is a tree indigenous to southeast
Asia.
 The pericarp rinds of the fruit have been used for
centuries in regional cooking practices and are
reported to make meals more filling and satisfying,
without any reported harmful effects.
 Commercially available Hydroxycitric acid (HCA) is
mainly extracted from the dried and cured
pericarp of the fruit of this species.
 Enhanced satiety may account for the reported
suppression of energy consumption

56.  Daily administration of a relatively low dose of
HCA (900 mg/day) over two weeks, reduced EI
and sustained satiety.
 Some clinical studies with HCA have encountered
mild adverse events such as headache, and
upper respiratory tract and GI symptoms

57. Phytochemicals that Block
Absorption
Some phytochemicals act by blocking the
breakdown and consequent absorption of
dietary carbohydrates and/or lipids, by
blocking the action of pancreatic lipase
and amylase enzymes in the GIT.

58.  Tea Cathechins
 Three kinds of tea: oolong, green, and black, are
widely used as traditional healthy drinks all over the
world.
 Green and Oolong tea have been reported to
have anti-obesity and hypo-lipidemic actions.
 Black tea also contains many active ingredients;
however some of these may not survive processing.

59.  Oolong Tea
 Catechins in oolong tea are reported to prevent
obesity by two main mechanisms: the inhibition of
small-intestine micelle formation and the inhibition
of α-glucosidase activity which would lead to a
decrease in carbohydrate absorption.
 In a double-blind, placebo-controlled study,
twelve weeks daily administration of oolong tea
(containing 690 mg of catechins) to normal and
overweight males produced a significant
reduction in body weight (1.5%), body mass index
(BMI) (1.5%), waist circumference (2.0%), and body
fat mass (3.7%), compared to the placebo group.

60.  Green Tea
 The long term consumption of green tea and its
extract (GTE, commercially available as pills,
patches, gums, mints, extracts, and ice creams)
have been associated with weight loss mainly
through a thermogenic mechanism.
 The main active ingredients in GTE – the catechins
are responsible for many of the beneficial effects of
green tea.
 Catechins from GTE have been associated with an
increase in sympathetic nervous system activity,
thermogenesis and fat oxidation in humans.

61.  Green Coffee Bean
 Green coffee bean extract (GCBE) contains 10%
caffeine and 27% chlorogenic acid as the principal
constituents.
 However, the roasting process of coffee drastically
reduces the level of chlorogenic acid and its
related compounds.
 The administration of instant coffee enriched with
chlorogenic acid to humans induced a reduction
in body fat and body mass at least in part due to a
reduction in the absorption of glucose.

62.  The reduction of glucose absorption would
ultimately lead to an increase in the consumption
of fat reserves.
 However, it is important to note that a major
consequence of blocking digestion of
carbohydrates in the proximal gut is colonic
fermentation which leads to increased microbial
production of gas in the bowel; this effect can limit
its use.

63.  Citrus Aurantium
 C. aurantium (Bitter Orange) contains alkaloids
such as p-octopamine and synephrines which
exert adrenergic agonist activity and are present
in supplements designed to aid weight loss.
 Synephrines could potentially increase energy
expenditure and decrease food intake.
 In addition, there is some evidence that C.
aurantium synephrines, decrease gastric motility.
 Overall, these studies reported a loss of 2.4–3.4 kg
among participants using synephrines, while
placebo groups lost 0.94–2.05 kg.

64. Phytochemicals that Decrease Body Weight
through both Central and Peripheral
Mechanisms
 Caffeine
 Caffeine is the most widely consumed
behaviourally active substance in the world.
 Almost all caffeine consumed comes from dietary
sources (beverages and food), most of it from
coffee and tea.
 The central effects of caffeine at habitually
consumed doses are due to its effects on the
widely distributed adenosine receptors.
 Caffeine also seems to exert thermogenic and
lipolytic actions.

65.  Nicotine
 Nicotine is an alkaloid naturally occurring in
tobacco leaves and is their major addictive
component.
 Similar to caffeine, nicotine exerts its effect through
central and metabolic actions.
 Among several effects, nicotine reduces appetite
and alters feeding patterns typically resulting in
reduced body weight.
 However, given the health and addiction issues
surrounding smoking, this is not a viable, healthy
weight reduction strategy!

66.  Khat
 Catha edulis, commonly called Arabian tea
or khat, is a flowering plant native to the Horn of
Africa and the Arabian Peninsula.
 Among communities from these areas, khat
chewing has a long history as a social custom
dating back thousands of years.
 Khat contains a monoamine alkaloid called
cathinone, an amphetamine-like stimulant, which
is said to cause excitement, loss of appetite and
euphoria.
 Cathinone compounds affect appetite centrally,
by acting in the hypothalamus.

67.  Apart from its central effect,
cathinone enhances
sympathomimetic activity
leading to a delay in gastric
emptying.
 In healthy volunteers, khat
chewing decreased hunger
and increased fullness
scores; this was associated
to a prolonged gastric
emptying which was
significant when compared
to lettuce chewing.

68.  Hoodia Gordonii
 Hoodia gordonii is a leafless spiny succulent
plant with medicinal properties. It grows naturally
in South Africa and Namibia.
 The flowers smell like rotten meat.
 The centuries-old use of the meat of the plant to
suppress appetite on long hunting trips in
the Kalahari Desert that has stimulated the most
interest.
 In 1977, the South African Council for Scientific and
Industrial Research (CSIR) isolated the ingredient in
hoodia—now known as P57—which is responsible
for its appetite-suppressant effect, and patented it
in 1996.

69.  H. gordonii P57 is commercially available as pills,
patches, and liquid.
 H. gordonii’s actions are mainly appetite
suppressant, anti-diabetic activity and delaying
of gastric emptying.

70.  Caralluma Fimbriata (Slimaluma)
 C. fimbriata is an edible succulent cactus that
belongs to the family Asclepiadaceae.
 Its key ingredients are pregnane glycosides, bitter
principles, saponins and various other flavonoids.
 The appetite suppressant and increased satiety
action of C. fimbriata could be mainly attributed
to the pregnane glycosides.
 In the adipose tissue, pregnane glycosides
reduces lipogenesis.

71.  In overweight humans, two months administration
of C. fimbriata extracts lead to a reduction in
appetite, body weight and waist circumference
when compared to a control group.
 Interestingly C. fimbriata selectively reduced the
intake of refined sugars, sweets, cholesterol and
saturated fats, without altering fruit, vegetable or
fish intake.

72.  Coleus Forskohlii
 Plectranthus barbatus, or more commonly known
as Coleus forskohlii and Indian Coleus, is a tropical
perennial plant related to the typical coleus
species.
 One of the main active compounds in C. forskohlii
is forskolin, a diterpene that acts directly on
adenylate cyclase.
 Adenylate cyclase is an enzyme that activates
cyclic adenosine monophosphate (cAMP), which
promotes lipolysis, increases the body's basal
metabolic rate, and increases utilisation of body
fat.

73.  Administration of
C. forskohlii extract
to overweight
women mitigated
weight gain with
no significant side
effects.

74. Phytochemicals that Increase
Appetite and Body Weight
 Cannabis Sativa
 Although the use of cannabis for medicinal
purposes dates back at least four thousand years,
understanding of the underlying pharmacology
dates back only forty years.
 Cannabinoids are known for their rewarding
effects and for their ability to stimulate increases
in food intake (e.g., the marijuana 'munchies').
 Cannabis hyperphagia is largely attributable to
actions at brain cannabinoid receptor.

75. Key Points
 Appetite control is a complex process of
peripheral GIT and central brain mechanisms.
 Many gut hormones and pancreatic hormones
play a role in appetite regulation.
 Adipose tissue also a significant endocrine organ.
 Many plants and herbs have long been used to
modify appetite.
 We are only now learning how they act on human
physiology.

76. Q?
Thank you