1
WHAT IS OBESITY? HOW DOES IT HAPPEN?
(Biesalki,H & Grimm,P. 2004, Pocket Atlas of Nutrition, Thieme)
 Page 274 Whitney for your definition.
 The stages involved in the development of
obesity are:
 Adipocyte volume increases.
 If caloric intake continues to exceed the
requirements, preadipocytes may be
transformed into additional adipocytes.
2
 Since the triglycerides deposited in these
adipocytes undergo constant metabolic
transformation, an increase in the levels of all
components of lipid metabolism ensues.
 The
resulting hyperlipoproteinemia and
hyperinsulinemia may lead to peripheral
insulin resistance.
3
4
 The cause of obesity is generally a sustained or
repeated positive energy balance. That is 
energy intake > energy requirements.
 Both sides of this equation are influenced by
exogenous factors:
 Intake is influenced by taste, upbringing,
environment during meals, psychological
factors, portion size and such.
 Requirements depend on physical activity at
work and during leisure.
5
 Both sides are also subject to heredity
components that have been shown to affect:
 Feeding behaviour
 Hunger and satiation
 Efficiency of cellular energy production
 Visceral fatty tissues have the highest metabolic
rate. Therefore the android form (apple shape)
of obesity tends to have more severe health
consequences.
6
 For purposes of evaluating obesity BMI tables
are usually used since they correlate with body
fat content.
 Revise the concepts of:
 Basal Metabolic Rate (BMR)
 Body Mass Index (BMI)
 Total Energy expenditure (TEE)
 Thermic Effects of food (TEF)
 Ways of assessing body fat distribution
 Do the practice calculation the following
slide.
7
 Calculate the Body Mass Index (BMI) for the following
based on the information provided.
Indicate the
classification of the BMI calculated (e.g. underweight,
normal, overweight, obesity, extreme obesity).
 Sex: female
Weight = 95 kg
Height = 160 cm
 Sex: male
Weight = 82kg
Height = 1.8 m
 WHAT DO YOU SEE AS THE LIMITATIONS OF THIS TYPE
OF MEASUREMENT?
8
 Refer to the Griffith Handbook for the BMI
classifications and associated health risks.
9
EPIDEMIOLOGY
 The following epidemiological information has
been sourced from a report by the Australian
Institute
of
Health
and
Welfare
at:
http://www.aihw.gov.au
 In the 2007–08 NHS, the majority of adults (61%)
had a body mass index (BMI) (based on
measured data) that indicated they were either
overweight or obese. A larger proportion of
males than females were overweight or obese
(68% compared with 55%) (Table 3.19).
10
11
 A person’s waist circumference can be used to
measure what is known as abdominal obesity.
Waist circumference is regarded as an
independent risk factor for Type 2 diabetes and
the risk increases with increasing waist
circumference (see Box 3.10).
 In 2007–08, almost 60% of Australian adults had
a waist circumference that put them at increased
risk of poor health, including 35% at a
substantially increased risk (see next slide). The
proportion of people at increased risk of poor
health due to their waist circumference increases
with age for both males and females.
12
13
 Excess weight in children increases the risk of poor
health, both during childhood and later in adulthood.
Children who are overweight or obese are at greater risk
of developing chronic conditions such as asthma and
Type 2 diabetes than those who are not. In addition,
children who are overweight or obese can experience
discrimination, victimisation and teasing that can affect
their psychological wellbeing.
 Recent estimates show that among children aged 5–17
years, 17% were overweight and 8% were obese. The
proportion of children who have excess weight is similar
in boys and girls, both peaking in the 9–13 years age
group (see over).
14
15
WHAT DOES ALL OF THIS
MEAN FOR US AS CAM
PRACTITIONERS?
16
OBESITY IS A KILLER
 In 2002, malignant neoplasm's, ischaemic heart
diseases and cerebrovascular diseases were the
leading underlying causes of death responsible
for 57% of all deaths. Obesity contributes
significantly to these deaths. (Eddy,S. 2005, Food as Medicine
presentation, Health Schools Australia)
 What are the major Australian obesity related
illnesses?
17
 Obesity causes cancer in women  “The
conversion of androstenedione secreted by
the adrenal gland into oestrone by aromatose
in adipose tissue provides an important
source of oestrogen for the postmenopausal
woman”. This oestrogen is thought to play an
important role in the development of
endometrial and breast cancer. (Eddy 2005)
18
 High carbohydrate consumption causes obesity
 The body will choose to metabolise
carbohydrates in preference to fats. However,
instead of consuming more carbohydrates,
remember that during carbohydrate feeding
lipolysis is significantly reduced, therefore fat
does not get broken down as needed. (Eddy 2005)
19
 A Harvard Nurses study in 2000 found that a high
intake of
rapidly digested
and
absorbed
carbohydrate increases the risk of coronary heart
disease (CHD) and that the low fat, high
carbohydrate diet may not be the best prevention of
CHD and could be responsible for increasing the risk
in individuals with insulin resistance and glucose
intolerance. (Eddy 2005)
 There is an increasing recognition that colorectal
cancer may be promoted by hyperinsulinemia and
insulin resistance suggesting that a diet that induces
high blood glucose levels and an elevated insulin
response may contribute to a metabolic environment
that is conducive to tumour growth. (Eddy 2005)
20
 Insulin stimulates pathways that increase
levels of insulin-like growth factor, and both
insulin and insulin-like growth factor promote
mitosis and cell proliferation but inhibit
apoptosis in normal and cancer cells of the
colonic epithelium. (Eddy 2005)
21
 What is actually is actually happening with our
dietary habits in the 21st Century? (Eddy 2005)
 Major movement towards “low fat”  however



Often high in carbs / sugar
Lacking in satiety
Larger portion required and craved
 Increase in convenience foods



Usually both high carbohydrate and high fat
Highly processed foods increase the amount
of trans fats consumed
Low in nutrients
22
23
 IMPLICATIONS OF THESE FACTS
FOR YOU IN CLINICAL PRACTICE
ARE?
 WHAT WILL YOU BE ADVISING
YOUR CLIENTS? WHY?
24
 More revision – what is white fat and brown fat
and how do they differ? And how do we benefit
from an understanding of how adipose tissue
works when trying to explain the obesity
epidemic?
25
 There are two types of adipose tissue
 White adipose tissue (unilocular) is coloured
white or yellow and has relatively few nerves
and blood vessels
 Each fat cell contains a single large droplet of
triglyceride that is coated with a protein
called perilipin
 White fat is used as a site for storing energy
for physical activity
 Leptin is generally produced in white fat
26
27
 Brown adipose tissue (multilocular) contains
more nerves and blood vessels
 Each brown fat cell contains several small
droplets of triglyceride, rather than one
large one.

Brown fat is used for heat production

Levels decrease with age
detectable in the 6th decade
but is still
28
29
Excess adipose tissue, especially white fat, leads
to reduced insulin sensitivity in metabolically
responsive tissues, which is frequently
associated with a set of cardiovascular risk
factors,
including
hyperinsulinemia,
hypertension,
dyslipidemia
and
glucose
intolerance.
30
 Therefore, our aim would be to increase the
levels
of
brown
adipose
tissue

↑thermogenesis  ↑metabolic rate and energy
consumption  the burning of white fat
31
Several molecules secreted by adipose tissue play a
critical role in this process of increasing metabolic rate:

Adiponectin

Leptin

Resistin

Interleukin 6
32
HOW?
 Adiponectin 
 ↑insulin sensitivity
 ↓ glucose
 Stimulates lipid catabolism
 Leptin 
 ↓glucose, insulin and lipids
 Stimulates lipid oxidation
33
LEPTIN
 Refer to page 277 of Whitney and come to an
understanding of the role that the hormone
Leptin plays in obesity.
 Page 278 explains the Ghrelin and its interaction
with leptin.
34
 Rats without functional leptin receptors and
mice without functional leptin proteins (ob/ob)
both exhibit characteristics of morbid obesity,
insulin resistance, delayed or impaired pubertal
development, and pituitaries with low numbers
of somatotropes or gonadotropes. (Crane,C., Akhter,N., Johnson,B et
al.2007, ‘Fasting and glucose effects on pituitary leptin expression. Is leptin a local signal for nutrient
status?’Journal of Histochemistry Cytochemistry, vol.55, iss.10, pp.1059–1073)
 Increased leptin in patients with lipodystrophy
results in less caloric, shorter, more satiating
meals and longer lived satiety. These data
support the hypothesis that leptin plays an
important, permissive role in human appetite
regulation. (McDuffie,J., Riggs,P., Calis,K et al. 2004, ‘Effects of Exogenous Leptin on Satiety
and Satiation in Patients with Lipodystrophy and Leptin Insufficiency’, Journal of Clinical Endocrinology
and Metabolism, vol.89, iss.9, pp.4258–4263)
35
 Leptin controls energy uptake and use by
regulating various satiety factors in the
hypothalamus, such as neuropeptide Y or
glucagon-like peptide 1. Since leptin is
synthesised in white adipocytes, fat mass
functions as a central control sensor. (Biesalki & Grimm
2004 p.37)
36
 When leptin is injected into leptin deficient
animals, it results in decreased food intake and
subsequent weight loss and the maintenance of
weight loss. Obese humans do not have a
deficiency of leptin, but surprisingly have higher
levels of circulating leptin in the body. This
would indicate that leptin deficiency is not a
primary cause of obesity, but rather a decreased
response to leptin.... In patients with morbid
obesity, an increase in leptin production by the
enlarged fat mass would be futile. (Wilborn,C., Beckham,J.,
Campbell,B. Et al. 2005, ‘Obesity: Prevalence, Theories, Medical Consequences, Management, and Research
Directions’ Journal of the International Society of Sports Nutrition, vol.2, iss.2, pp.4–31)
37
Adiponectin
 Adiponectin is an adipose cell messenger
(adipocytokine) and is the link between obesity
and insulin resistance. It is secreted by adipose
tissue and circulated in the blood.
 Adiponectin concentrations correlate strongly
with the concentration of HDL cholesterol and
LDL particle size.
38
 As an insulin sensitizer, adiponectin is shown to
enhance insulin sensitivity through increases in
fatty acid oxidation and insulin-mediated
glucose disposal as well as decreases in hepatic
gluconeogenesis and glucose output.
 It has also been shown that the role of
adiponectin in positively influencing HDL and
triglyceride levels is attributed to adiponectininduced activation of the transcription factor
peroxisome proliferator-activated
receptoralpha (PPAR-a) which lowers triglycerides and
increases HDL by increasing the expression of
genes involved in metabolism of lipids and
apolipoproteins. Patel et al 2006; Fruchart et al 2001; Yamauchi et al 2003
39
40
 There is increasing evidence for a causal link
between adiponectin and insulin sensitivity
that is medicated via receptors that promote
glucose uptake and metabolism in the liver. (Singhal
et al 2005)
 Therefore, an adverse effect of low adiponectin
concentration on muscle fatty oxidation could
impair insulin sensitivity in the young before
the onset of clinical obesity.
 Adiponectin’s downstream metabolic effects
include stimulation of glucose utilisation and
fatty acid oxidation by activation of AMP-
activated protein kinase.
41
 Adiponectin levels are, on the average,
considerably higher in women than men and
women and men have a marked difference in
body fat distribution.
 Because adiponectin is secreted by adipocytes
and is closely related to glucose metabolism
and given the sex differences in these risk
factors, its effect on CHD differs between men
and women. (Lawlor et al 2005)
42
 These higher levels of adiponectin in women
compared with men and the greater effects of
hyperglycaemia on CHD in women compared with
men may reflect a relative resistance to the effect of
adiponectin in women.
 Also, added to this is that in vivo studies are
suggesting that the molecular forms of adiponectin
may differ between males and females with women
having greater concentrations of the high molecular
weight form of adiponectin than men but with lesser
amounts of the other molecular forms. Again, more
research is needed to see if this helps to explain any
sexual dimorphism in the adiponectin – CHD
relationship.
43
 in skeletal muscle adiponectin has been shown
to ↓ tissue triglyceride content by ↑ utilisation of
fatty acids as a fuel source
44
THEREFORE - ADIPONECTIN:
↓Hepatic glucose output
↑Fatty acid oxidation in muscle and liver
With an overall ↓ in triglycerides
47
AND
Adiponectin:
Reduces central fat accumulation
AND
Low adiponectin levels may induce alterations in
the insulin response
48
What is PPAR-а and ỵ
 Peroxisome
proliferator-activated
receptor
(PPAR) [pronounced p-par] are nuclear hormone
receptors that, when activated, exert different
functions and plays a key role in the regulation
of genes involved in carbohydrate, lipid and
lipoprotein metabolism
 There are 3 PPAR subtypes
 Gamma (y)
 Alpha (a)

Delta (δ)
49
 PPAR-y is highly expressed in adipocytes where
it mediates cell differentiation and promotes
lipid storage
 Activation of PPAR-y results in improved
insulin sensitisation and enhanced glucose
disposal in adipose tissue and skeletal muscle
50
 PPAR-y agonists acts by improving lipid and
insulin function by sequestering lipid within
the triglyceride droplet in adipose tissue
 It is believed that this will protect skeletal
muscle, liver and beta cells (from the pancreas)
from excess lipid supply
 PPAR-y agonists act by
 Decreasing Free Fatty Acids (FFA’s) in the
blood
 Increasing insulin stimulated lipid storage
51
 PPAR-a is activated by polyunsaturated fatty
acids and is implicated in
 the regulation of lipid metabolism
 lipoprotein synthesis and metabolism
 an inflammatory response in liver and other
tissues
 Activation of PPAR-a results in
 decreased plasma levels of triglycerides
 increased plasma HDL cholesterol levels
 May stimulate reverse cholesterol transport
52
The PPAR Family
Ligand
Receptor
Leukotrienes
Fibrates
Prostaglandins
Thiazolidinediones
Fatty Acids
PPAR
PPAR
PPAR /
HDL Reverse
Cholesterol Trans
Fat Oxidation
Effect
Vascular Effects
Fat Oxidation
Fat
Differentiation/
Redistribution
Glucose
Metabolism
Adapted from Saltiel AR, Olefsky JM. Diabetes. 1996;45:1661-1669.
http://www.lejacq.com/Symposia_Info/UMH_NY-0306/Giles.ppt#23
53
HOW?
 4-wk supplementation of conjugated linoleic acid
(CLA) showed a significant reduction of serum leptin
concentration (42%) ..... As well there was a 5.2%
decrease in body weight..... CLA enhanced activity in
brown adipose tissue ..... (Rahman,S. Et al. 2001, ‘Effects of conjugated linoleic acid on
serum leptin concentration, body-fat accumulation, and β-oxidation of fatty acid in OLETF rats’, Nutrition, vol.17, iss.5,
pp.385 - 390)
 Dietary Conjugated Linoleic Acid supplementation
has resulted in a dramatic decrease in body fat mass
in mice..... decreased the blood glucose and insulin
levels, and improved insulin resistance..... reduced
weight gain and perigenital fat pad weight..... Can
reduce leptin levels. (Zhou,XR., Sun,CH, et al 2008, ‘Dietary conjugated linoleic acid increases
PPARy gene expression in adipose tissue of obese rat, and improves insulin resistance’, Growth Hormone & IGF Research)
54
 Refer back to earlier revision to discuss how
best to ↑thermogenesis
 In this study it was found that irregular
meal frequency led to a lower postprandial
energy expenditure compared with the
regular meal frequency, while the mean
energy intake was not significantly different
between the two. The reduced TEF (thermal
effect of food) with the irregular meal
frequency may lead to weight gain in the
long term. (Farshchi,HR., Taylor,MA., Macdonald,IA. 2004, ‘Decreased thermic
effect of food after an irregular compared with a regular meal pattern in healthy lean women’,
International Journal of Obesity and Related Metabolic Disorders, vol.28, iss.5, pp.653-60)
55
 In this study, it was found that regular eating
was associated with lower Energy Intake,
greater postprandial thermogenesis, and lower
fasting total and LDL cholesterol. Fasting
glucose and insulin values were not affected by
meal pattern, but peak insulin concentrations
and area under the curve of insulin responses
to the test meal were lower after the regular
than after the irregular meal pattern. It was
therefore concluded that regular eating has
beneficial effects on fasting lipid and
postprandial
insulin
profiles
and
thermogenesis. (Farshchi,HR., Taylor,MA., Macdonald,IA. 2005, ‘Beneficial metabolic
effects of regular meal frequency on dietary thermogenesis, insulin sensitivity, and fasting lipid profiles in
healthy obese women’, American Journal of Clinical Nutrition vol.81, iss.1, pp.16-24)
56
 Green tea has been shown to increase Resting
Energy Expenditure by 372kJ/day, or about
one-fourth of moderate exercise..... There is
evidence that green tea polyphenols depress
leptin levels ..... the consumption of green tea
extract elevates both the metabolic rate and
the rate of fat oxidation ..... In conclusion,
green tea capsules in a dosage of 100mg/day
EGCG can increase energy expenditure and fat
oxidation in obese subjects in 12weeks period.
(Auvichayapat,P., Propochanung,M et al 2008, ‘Effectiveness of green tea on weight reduction in obese Thais:
A
randomised,
controlled
trial’,
Physiology
&
Behaviour,
vol.93,
iss.3,
pp.486-491)
57
 Carbohydrates inhibit leptin  The postprandial
leptin response is lower after a carbohydrate
meal in obese women than in lean controls,
suggesting an impairment of postprandial leptin
regulation in obese women. (Eddy 2005)
 Triglycerides
cause leptin resistance 
Triglycerides are an important cause of leptin
resistance as mediated by impaired transport
across the BBB and suggest that triglyceridemediated leptin resistance may have evolved as
an anti-anorectic mechanism during starvation.
Decreasing triglycerides may potentiate the
anorectic effect of leptin transport across the
BBB. (Eddy 2005)
58
 Insulin reduces leptin  overweight and obese
PCOS subjects appear to produce insufficient
leptin for a given fat mass and this was found to
be relative to the degree of hyperinsulinaemia,
potentially because of the leptin reducing effects
of adipocyte insulin resistance. (Eddy 2005)
59
 Other nutritional considerations that could be
part of obesity treatment are:
 Alpha-lipoic acid utrients and re

The type of fat, rather than the amount of
fat, in the diet may be more important in
terms of determining health outcomes.
Many studies have shown that the long chain
n-3 polyunsaturated fatty acid found in oily
fish and fish oil possess cardioprotective
effects
and
α-lipoic
acid
possesses
antioxidant property with improving insulin
sensitivity. (Wu,CJ & Yu,ZR. 2004, ‘Effects on blood glucose, insulin, lipid and
proatherosclerotic parameters in stable type 2 diabetic subjects during an oral fat challenge’, Lipids in
Health and Disease, vol.3, iss.17)
60
 L-carnitine 

It plays a central role in both fat and
carbohydrate
metabolism.
By
manipulating the carnitine in skeletal
muscle at rest, both physiologically and
pharmacologically, it is possible to
regulate
skeletal
muscle fat
and
carbohydrate oxidation, both at rest and
during exercise. (Stephens,F., Constantin-Teodosiu,D & Greenhaff,P.
2007, ‘New insights concerning the role of carnitine in the regulation of fuel metabolism in
skeletal muscle’ Journal of Physiology, vol. 581(Pt 2), pp. 431–444)
61
 Other suggestions include: Explain why
 Antioxidants
 Co Enzyme Q10
 Ascorbic acid
 Vitamin E
 Polyunsaturated fatty acids
 If time permits – map out what you have learnt
about the physiology of obesity and how you
can use this knowledge to benefit your clients.
62
Interventions
 Refer to page 283 of Whitney
63
Eating plans and exercise
 Refer to page 288 – 295 of Whitney
64