OBESITY AND ITS BIOCHEMICAL

INVESTIGATIONS
IDOWU ENIOLA MOTUNRAYO
 OUTLINE
 Introduction
 Definition
 Epidemiology
 Mechanism
 Causes
 Classification
 Clinical features
 Childhood Obesity
 Metabolic Syndrome
 Complications
 Investigations
 Treatment
 Conclusion and References
 INTRODUCTION
 Obesity is defined as the medical
condition involving accumulation of
excessive body fat which leads to
increased risk of health problems
 It is the net result of excessive energy

intake compared to energy usage

 People are generally considered obese

when their body mass index (BMI), a

measurement obtained by dividing a
person's weight by the square of the
person's height, is over 30 kg/m2.
 Introduction
 BMI is defined as the subject's weight
divided by the square of their height and is
calculated as follows.
BMI =m/h²
where m and h are the subject's
weight(kilograms) and height(meters)
respectively.
 BMI is usually expressed in kilograms of

weight per metre squared of height (kg/m2).

 EPIDEMIOLOGY
 Obesity is a leading preventable cause of death
worldwide, with increasing rates in adults and
children. In 2015, 600 million adults (12%) and
100 million children were obese in 195 countries.
 Obesity is more common in women than men.
Authorities view it as one of the most serious
public health problems of the 21st century.
 In 2013, several medical societies, including the
American Medical Association and the American
Heart Association, classified obesity as a disease.
CLASSIFICATION OF BODY MASS INDEX (BMI)
 Classification
The most commonly used definitions, established by
the World Health Organization (WHO) in 1997 and
published in 2000, provide the values listed in the
table.
 The surgical literature breaks down class II and

class III obesity into further categories whose

exact values are still disputed:
Any BMI ≥ 35 or 40 kg/m2 is severe obesity.
A BMI of ≥ 35 kg/m2 and experiencing obesity-
related health conditions or ≥40–44.9 kg/m2 is
morbid obesity.
A BMI of ≥ 45 or 50 kg/m2 is super obesity.
 Classification
Some nations have redefined obesity;
 Japan has defined obesity as any BMI greater

than 25 kg/m2 while China uses a BMI of greater

than 28 kg/m2.
Note: An alternative approach to access obesity is
to:
Measure the waist circumference and / hip
circumference;
 with 88 cm for females and 102 cm for males Or

a waist/hip ratio of greater than 0.9 in men and

0.85 in women being indicative of abdominal
obesity in adults.
 Mechanism
There are Environmental, Genetic and Molecular
Mechanisms

 Chronic diseases and obesity emerged as leading

health concerns over the past century through
shared environmental changes.
 Genes can contribute to obesity by causing
abnormalities of:
1. One or more of the pathways that regulate the
feeding centers and
2. Energy expenditure and fat storage
 Mechanism
 Leptin, a 16-kDa protein that is expressed in
adipocytes, is an afferent signal that relays the
magnitude of the fat stores to the central nervous
system, primarily the hypothalamus, and plasma
levels correlate with the adipose tissue mass.
 Adiponectin is another adipose-released hormone
that is thought to sensitize tissues to insulin.
 Neuropeptide Y is a potent stimulator of food
intake, the production of which is inhibited by
leptin.
 Obese humans paradoxically have high levels of
leptin, presumably because of tissue resistance to
it.
 Mechanism
 Pro-opiomelanocortin is also involved in obesity and is
cleaved to form adrenocorticotrophin and a-
melanocyte-stimulating hormone (MSH).
 The latter acts on the melanocorticortin-4 receptor
(MC4-R) in the hypothalamus, which in turn increases
energy expenditure and reduces food intake.
 Agouti protein, which is also expressed in hair
follicles, antagonizes the actions of MSH by blocking
MC4-R.
 Also involved in obesity is the β-3-adrenoreceptor,
which mediates adipose metabolism by the
sympathetic nervous system.
 Causes
 Diet
 Sedentary life style
 Genetics
 Gutbacteria
 Medications
 Other illnesses
 Other causes
 Diet
 Consumption of high calorie and fat rich food,
sweetened drinks are believed to be contributing
to the rising rates of obesity and to an increased
risk of metabolic syndrome and type 2 diabetes.

 Vitamin D deficiency is related to diseases

associated with obesity.

 As societies become increasingly reliant on

energy-dense, big-portions, and fast-food
meals, the association between fast-food
consumption and obesity becomes more
concerning.
 Sedentary life style
 A sedentary lifestyle plays a significant role in
obesity.
 Worldwide there has been a large shift towards
less physically demanding work, mechanized
transportation and a greater prevalence of
labor-saving technology in the home .
 The World Health Organization indicates people
worldwide are taking up less active recreational
pursuits.
 Currently at least 30% of the world's population
gets insufficient exercise.
 Genetics
Polymorphisms in various genes controlling appetite and
metabolism predispose to obesity when sufficient food energy is
present.

 Four of the monogenic (single-gene) causes of obesity are:

1. Mutations of MCR-4, the most common monogenic form of
obesity discovered thus far;
2. Congenital leptin deficiency caused by mutations of the
leptin gene, which are very rare;
3. Mutations of the leptin receptor, which are also very rare.
4. People with two copies of the FTO gene (fat mass and obesity
associated gene) have been found on average to weigh 3–4 kg
more and have a 1.67-fold greater risk of obesity compared
with those without the risk allele.
 Genetics
 Studies that have focused on inheritance
patterns rather than on specific genes have
found that 80% of the offspring of two
obese parents were also obese, in contrast
to less than 10% of the offspring of two
parents who were of normal weight.

 Different people exposed to the same

environment have different risks of obesity
due to their underlying genetics.
 Gut bacteria
 The study of the effect of infectious agents on
metabolism is still in its early stages.
 Gut flora has been shown to differ between lean
and obese people. There is an indication that gut
flora can affect the metabolic potential. This
apparent alteration is believed to confer a greater
capacity to harvest energy contributing to obesity.
Whether these differences are the direct cause or
the result of obesity has yet to be determined
unequivocally.
 The use of antibiotics among children has also
been associated with obesity later in life.
 Medications
Certain medications may cause weight gain or
changes in body composition; these include
 Insulin,

 Sulfonylureas,

 Thiazolidinediones,

 Atypical antipsychotics,

 Antidepressants,

 Steroids,

 Certain anticonvulsants (phenytoin and

valproate),
 Pizotifen, and

 Some forms of hormonal contraception.

 Other ilLnesses
 Obesity is a major feature in several
syndromes, such as:
 Prader–Willi syndrome,
 Bardet–Biedl syndrome,
 Cohen syndrome, and
 MOMO syndrome.

(The term "non-syndromic obesity" is

sometimes used to exclude these
conditions.)
 Other ilLnesses
 Some congenital or acquired conditions:
hypothyroidism, Cushing's syndrome, growth
hormone deficiency,
 Some eating disorders: binge eating disorder and
night eating syndrome.

 However, obesity is not regarded as a psychiatric

disorder, and therefore is not listed in the DSM-IVR
as a psychiatric illness. The risk of overweight and
obesity is higher in patients with psychiatric
disorders than in persons without psychiatric
disorders.
 Other causes
 Insufficientsleep,
 endocrine disruptors (environmental

pollutants that interfere with lipid

metabolism),
 Increased use of medications that

can cause weight gain (e.g., atypical

antipsychotics),
 Other causes
 pregnancy at a later age (which may cause
susceptibility to obesity in children),
 epigenetic risk factors passed on generationally,
 natural selection for higher BMI, and
 assortative mating leading to increased concentration
of obesity risk factors (this would increase the number
of obese people by increasing population variance in
weight).
 According to the Endocrine Society, there is "growing
evidence suggesting that obesity is a disorder of the
energy homeostasis system, rather than simply arising
from the passive accumulation of excess weight".
 Clinical features
The more common symptoms seen in obese
individuals are as follows:
 Fatigue/tiredness on exertion.
 Exertional dyspnoea, weakness, malaise.
 Symptoms of reactive hypoglycaemia like

weakness, palpitation, sweating, often seen in

obese and adult onset diabetics about 3 to 5
hours after meals.
 Excessive weight gain in spite of normal or

reduced calorie intake

 Excessive hunger
 Clinical features
Signs:
 Pink striae are commonly seen over abdomen, thighs, buttocks,

breasts, particularly in young women, pink colour usually

disappears leaving shiny and white striae.
 When obesity is massive, exertional dyspnoea and tachypnoea

may be seen.
 Intertrigo is quite common in the folds below the breast and in

the inguinal regions.

 Plethora involving the cheeks and neck is not unusual.

 Blood pressure is usually normal. Sometimes systemic

hypertension may be present due to associated disorders like

DM.
 Occasionally ankle oedema may be noted.
 Childhood obesity
As with obesity in adults, many factors contribute to the rising
rates of childhood obesity.
 Changing diet and decreasing physical activity are believed

to be the two most important causes for the recent increase

in the incidence of child obesity.
 Antibiotics in the first 6 months of life have been

associated with excess weight at age seven to twelve years

of age.
 Because childhood obesity often persists into adulthood

and is associated with numerous chronic illnesses, children

who are obese are often tested for hypertension, diabetes,
hyperlipidemia, and fatty liver disease.
 Treatments used in children are primarily lifestyle

interventions and behavioral techniques, although efforts to

increase activity in children have had little success
METABOLIC SYNDROME
 Also known as Dysmetabolic syndrome, Insulin
resistance syndrome, Syndrome X, is a cluster
of at least three of the following medical
conditions;

◦ Abdominal obesity
◦ High blood pressure
◦ High blood sugar
◦ Low HDL levels
◦ High serum triglyceride
 Complications
Obesity increases the likelihood of
various diseases and conditions :
 Cardiovascular diseases,
 Type 2 diabetes,
 Obstructive sleep apnea,
 Certain types of cancer,
 Osteoarthritis, and
 Depression.
 Treatment
 Diet and physical exercise
 The main treatment for obesity consists of weight
loss via dieting and physical exercise.
 Dieting, as part of a lifestyle change, produces
sustained weight loss, despite slow weight regain
over time. Intensive behavioral interventions
combining both dietary changes and exercise are
recommended. Several diets are effective.
 In the short-term low carbohydrate diets appear
better than low fat diets for weight loss. In the long
term, however, all types of low-carbohydrate and
low-fat diets appear equally beneficial
 Treatment
 Surgery
 The most effective treatment for obesity is

bariatric surgery. The types of procedures

include laparoscopic adjustable gastric
banding, Roux-en-Y gastric bypass, vertical-
sleeve gastrectomy, and biliopancreatic
diversion.
 Surgery for severe obesity is associated with

long-term weight loss, improvement in

obesity-related conditions, and decreased
overall mortality
Treatment
 Drugs
 Some new drug therapies are available, but

these should not be viewed as a universal

panacea for obesity.
 one of such drug is Orlistat: a pancreatic

lipase inhibitor that caused reduced small

intestine fat absorption.
 Other therapeutic possibilities in future may

be neuropeptide Y antagonists, leptin

analogies and B-3-adenoreceptor agonists.
Biochemical investigation of Obesity

Standard laboratory studies in the

evaluation of obesity should include the
following:
 Fasting lipid profile
 Liver function studies
 Thyroid function tests
 Fasting glucose and hemoglobin A1c

(HbA1c)
Biochemical investigation
Lipid Profile
At least, fasting cholesterol, triglycerides, and
high-density lipoprotein cholesterol (HDL-C)
levels. These levels may be normal, or the
typical dyslipidemia associated with
cardiometabolic syndrome may be found.
 This dyslipidemia is characterized by

reduced HDL-C and elevated fasting

triglyceride concentrations.
Biochemical investigation
Glucose and insulin studies
 Obesity is associated with insulin resistance

and increased serum levels of fasting insulin

and C-peptide serum levels.
 However, insulin levels are normal in many

persons who are obese.

 All patients with obesity should be screened

for diabetes. Additional information is gained

by using glucose and HbA1c tests together if
the patient is fasting
 Biochemical investigation
Liver and thyroid function tests
 Liver function tests yield normal results in

most obese patients.

 However, elevated transaminase levels may

indicate nonalcoholic steatohepatitis (NASH) or

fatty infiltration of the liver).

 Thyroid function test results are also typically

normal, but checking them to detect primary
hypothyroidism because hypothyroidism can
causes mild obesity.
 Anti-obesity vaccine
 Scripp’s vaccine: An anti-obesity vaccine that
significantly slows weight gain in experimental
mice, by tackling the “ghrelin”, a naturally
occurring hormone that helps regulate energy
balance in the body. Scripp’s vaccine has yet to be
tried in humans.

 Cytos antiobesity vaccine: The cytos vaccine

works in a different way than the Scripp’s vaccine,
preventing the uptake of ghrelin by the brain.
 Conclusion

 Although about 1 billion of the world’s

population are undernourished,
approximately 1 billion are
overweight.
 Obesity is increasing, particularly in

Western urbanized societies

References
 Clinical biochemistry and metabolic medicine
(Martin A Crook)
 Kumar and Clark’s Clinical Medicine 8th

Edition.
 Medicinenet.com/obesity_and_weigh_loss by

Jerry R. Balentine, DO, FACEP

Thank YOU