Overnutrition I

Physiology of weight regulation

Michael Boyne
Tropical Medicine Research Institute
University of the West Indies, Mona
 Angie
Angie is a 32 year old woman who has been struggling with her weight
for many years. She was overweight as a child, but this worsened
during her adolescence. She says that she eats like a bird and she
is confused how she could have gained so much weight. She thinks
there is something wrong with her metabolism. She takes several
medications for hypertension, hyperlipidaemia, and osteoarthritis (i.e.
amlodipine, lisinopril, atorvastatin and ibuprofen), and she also has
obstructive sleep apnea.

She lives with an overweight consort and they have been trying
unsuccessfully for 5 yrs to have a child. Her fertility evaluation is said to
be normal although she has irregular menses. She is convinced that
she needs to lose weight at all costs to improve her health and her
chances of becoming a mother. She works as a telephone operator,
has a long commute to work from Portmore, rarely exercises because
of her arthritis and she "does not like gyms." She buys her lunch at
work and there is no evening meal-planning by her consort who does
the majority of cooking.

Her weight is at least 160 kg which is the maximum weight recorded by

the scale. Her height is 157 cm and her waist circumference is 140 cm.
Apart from a very obese abdomen, her physical examination is
unremarkable
Is Angie obese? How do you know if
she is obese?

Obesity is just like

pornography

Its hard to define but I

know it when I see it
Justice Potter Stewart, 1964
Jean-Auguste-
Dominique Ingres
1780-1867
The Turkish Bath
1862

Harmensz
Rembrandt van
Rijn
1606-1669
Bathsheba
1654 Antonio Allegri, known
as Correggio
1489?-1534
Venus, Satyr and Cupid
 Classification of obesity:
Body mass index
Grade Degree of BMI
Obesity
3 Morbid obesity > 40
2 Obesity 30-40
1 Overweight 25-29.9
0 Normal weight 18.5-24.9

Children > 95th centile for BMI

 Natural Progression of Weight Gain
Fat content: women> men
Gradual increase from pre-puberty to 60s then age-related loss

Eckel R H et al. JCEM 2011;96:1654-1663

 Global Prevalence Rates of
Undernourishment and Obesity

Source: FAO for prevalence of undernourishment. Population Health Metrics 10 (22): 1-16 (2012).
 Global Burden of Obesity in 2005
and Projections to 2030

Int J Obes 32: 1431-37 (2008).

 Age-adjusted prevalence of obesity
in the African diaspora
Men Women

50
Prevalence (%)

40
30
20
10
0

USA
UK
Nigeria

Barbados
St. Lucia

Jamaica
Cameroon

Obes Rev 1995; 3: 95-105S

 Worsening adiposity in Jamaicans

+ 7 kg increase in men
Luke 2001 + 14 kg in women
 Weight change in the African Diaspora

Nigeria Jamaica USA

3
Weight change (kg/yr)

2.4
2.5
2
1.5 1.16 1.2 1.19

1
0.43
0.5 0.25 0.19

0
-0.05
-0.5 <25 25-29 30+
-1 -0.77

BMI category (kg/m2)

BMC Public Health. 2008;8(1):133.
Obesity epidemic strikes U.S. pets
CNN February 4, 2012

41 million dogs and 47 million

cats are overweight or obese
53% of adult dogs and 55% of
cats were overweight or obese
25% of cats and 21% of dogs are
obese
HTN, arthritis, T2DM, cancers,
life span shortened by 2-2.5
years
What are the health consequences of
overweight?
 Prevalence of hypertension and
mean BMI in African diaspora

35
Maywood
% Hypertension

30

25 Barbados
St. Lucia
Jamaica
20

15 Cameroon urban
Cameroon rural
10 Nigeria
22 24 26 28 30 32
Body mass index

Am J Public Health 1997;87:160-8

 Complications of Obesity
Mortality
Pulmonary disease 1-14 years lost Idiopathic intracranial hypertension
abnormal function Stroke
obstructive sleep apnea Cataracts
hypoventilation syndrome
Nonalcoholic fatty liver Coronary heart disease
disease Diabetes
steatosis
Dyslipidemia
steatohepatitis
Hypertension
cirrhosis
Gall bladder disease Severe pancreatitis
Gynecologic abnormalities
abnormal menses Cancer
infertility SCFE breast, uterus, cervix
polycystic ovarian syndrome colon, esophagus, pancreas
kidney, prostate
Osteoarthritis
Skin

Gout Phlebitis
venous stasis
 Y-Y Paradox:
Limitations of BMI across populations

Yajnik CS and Yudkin JS. Lancet 2004: 363: 163

 20

Brown/beige fat
Visceral Fat Distribution:
Normal vs Type 2 Diabetes

Normal Type 2 Diabetes

 Insulin Resistance:
Causes and Associated Conditions
Aging
Obesity and Medications
inactivity
Rare
Genetics
disorders
INSULIN
RESISTANCE
Type 2
PCOS
diabetes
Hypertension Atherosclerosis
Dyslipidemia
 23
Obesity and Metabolic Risk
Abdominal vs. Peripheral Obesity

Large Insulin-Resistant Menopause

Adipocytes

Small Insulin-Sensitive
Adipocytes

Android Obesity Gynoid Obesity

Sharma 2002
Link between abnormalities in WAT (white adipose tissue)
and other organs and diseases associated with obesity

Biochem. J. 2010;430:e1-e4
Quality of Life for Obese*
Children and Adolescents
Obesity Predicts Depression:
Prospective Data
 How did her Obesity develop?
Pathogenesis of Obesity

Secondary causes e.g. Cushings rare

Is primary obesity due to:
Energy intake or energy expenditure?
Under-reporting of intake is common
Obese by 34-54%
Lean subjects 0-20%
 Causes of Obesity:
Do you like Angie?

X
Sloth

Gluttony

Riotous living
Are Genetic Factors the Cause of Obesity?

Genes vs. shared environmental influences

Polygenic and not Mendelian: seen in twin
studies
SNPs in FTO, MCR4
Effect is small, and heredity is not destiny
Monogenic syndromes are rare, e.g. Prader-
Willi, Carpenter, Leptin deficiency, Alstrom
 Energy Balance: C

Intake vs Expenditure
 Feedback Control of Energy Intake

70 kg man maintaining weight x 10 yrs: 98% accuracy

100 kcal/day = 10 lb/yr
9 kg increase over 30 yrs ~ 0.3% kcal excess
eating like a bird
After caloric loading or deprivation, animals adjust
intake to reach same weight
Ventromedial hypothalamus
 Short-term influences on food intake:
We eat for non-physiological reasons!

Input from higher brain centres: voluntary

control, psychosocial issues, emotional factors
Environmental factors: environmental
threats, food availability, food palatability,
energy required to obtain food
Metabolic/autonomic input: glucose
metabolism, SNS function
Satiety signals: gastric stretch, gut peptides
Diet has changed
 Fat as the Macronutrient Culprit?
Carbohydrat
Protein
e Fat

Energy content per g 4 4 9

Ability to end eating High Moderate Low

Ability to suppress hunger High High Low

Storage capacity Low Low High

Pathway to transfer excess

Yes Yes No
to alternative compartment
Ability to stimulate own
Excellent Excellent Poor
oxidation

Adapted from WHO Consultation 1998

Energy density and total energy intake
is our enemy

Whopper
660 kcal
Large Fries 400 kcal
Soda 150 kcal
Total 1210 kcal

Patty 300-450 kcal Candy bar 225 kcal 1 cookie 50 kcal

How long does it takes for you to
burn.?
Adipostatic model of weight regulation
Ghrelin, GLP-1, GIP, PYY,

Adipokines
 Control of Meals

Scant evidence that meal initiation is

controlled by metabolic or hormonal signals

Best evidence is that under normal

circumstances, meal initiation is based
upon learned associations
Compelling evidence that meal cessation
(meal size) is controlled by preabsorptive
gut signals
If only it were so easy!

Liporex
Lipotrim
Cortislim
Relacore
Cortaway
Cortigen
Cortislender
Cortiblock, etc.
Germs That Are Good For You
Role of energy expenditure
 Energy expenditure declines with ageing
Intense
Discretionary Occupational
exercise
Sitting, coffee, Dietary induced Basal metabolic
smoking thermogenesis rate
4000

3000

2000

1000

0
70 kg, Aged 25 years 70 kg, Aged 70 years
James, Ralph and Ferro-Luzzi, 1989
Is Angies metabolic rate low?
 Physical activity has changed:
NEAT has declined precipitously
 Markers of inactivity related to
obesity incidence
% Obese Cars/household TV viewing (hours/week)
200
% of Mean of All Time Points

100

0
1950 1960 1970 1980 1990

Prentice AM, BMJ 1995;311:437-9

Television Watching
and Risk of Obesity
Emerging as an
important factor
with our changing
work environment
 High-Tech increases Body Weight
Cellular phones and remote controls
deprive us from walking!

20 times daily x 20 m = 400 m

Walking distance lost/year

400x365 = 146,000 m

146 km = 25 h of walking

1 h of walking = 113-226 kcal

Energy saved =2800-6000 kcal (= 1 extra lump of sugar/day)

0.4-0.8 kg adipose tissue

Rssner, 2002
We need to prescribe physical
activity and energy intake
What do you think about her weight
problems during childhood?

Does this provide insight into her

problem?
Intergenerational cycle of overweight and
obesity
ELDERLY Men
PEOPLE overweight
overweight Metabolic Women Tracking
syndrome

High birth weight

ADOLESCENTS
Low birth overweight
weight
followed by Infants Reduced Energy-dense
rapid breastfeeding diets and low levels of
weight gain physical activity

Tracking Tracking

CHILDREN
overweight
Women
Poor nutrition
Adapted from Challenge of obesity in WHO European Region
and strategies for response: Summary; WHO 2007
Could any of her medications be
increasing her weight?
 Drugs that cause weight gain

glucocorticoids
progestins
tricyclic antidepressants
phenothiazines
2nd generation anti-psychotics
lithium
insulin
sulphonylureas
HAART
anti-epileptic agents
Not low-dose oestrogens!
 Predictors of weight gain
1. parental overweight 9. stress (inc. high
2. lower SES cal/carb foods)
3. smoking cessation 10. multiple births
4. low level of physical 11. endocrine disruptors
activity (phthalates)
5. infancy and childhood 12. gut microbiota
overweight 13. perception of body
6. lack of parental image
knowledge of childs 14. overweight/obese
sweet eating habits social network
7. recent marriage 15. Food policy and
8. lack of sleep security
 Principle components of body weight
regulation in an obesogenic environment
Americans enjoy one of the most luxurious lifestyles on Earth:
Our food is plentiful. Our work is automated. Our leisure is
effortless. And it's killing us.
 NHLBI recommendations for weight
treatment

BMI category

Treatment 25-26.9 27-29.9 30-34.9 35-39.9 40

Lifestyle If chronic If chronic + + +

modification illnesses illnesses

Pharmacotherapy - If chronic + + +
illnesses

Bariatric surgery - - - If chronic +

illnesses
 Little difference between low-carb or low-fat diets for
weight loss (48 unique RCTs with 7286 persons).
Hence, recommend any diet that a patient will adhere to
in order to lose weight.

JAMA. 2014;312:923-933.
 Drug Therapy
chronic treatment sibutramine
1st generation dexfenfluramine
modest efficacy
no long-term f/u Initial responders
individuals with co- continue to respond;
morbidities initial non-responders
complements but are less likely
doesnt replace life
style modifications
 Drug Therapy: Systematic Review
and Meta-analysis
Phentermine Liraglutide Naltrexone- Lorcaserin Orlistat
- topiramate (Victoza) bupropion (Belviq) (Xenical,
(Qsymia) Alli)

5% 75% 63% 55% 49% 44%

weight loss
Weight
loss cf 8.8 kg 5.3 kg 5.0 kg 3.2 kg 2.6 kg
placebo at
1 yr
D/C due to ++ ++ + + +
AE

JAMA. 2016 Jun 14;315(22):2424-34.

Types of bariatric surgery