Biochemical aspects of obesity

A lucid presentation on Biochemical aspects of obesity for medical , dental , pharmacology and biotechnology students to facilitate easy-learning.

1. Biochemical aspects of Obesity
Dr. Rohini C Sane

2. Types of Malnutrition
•Undernutrition
•Over nutrition (obesity): the most prevalent nutritional
disorder in prosperous developed countries and in
affluent people.

3. Obesity
•Obesity : refers to a condition in which the body weight is 20% or more
than the ideal body weight. It is the prevalent Nutritional Disorder when
excess fat gets accumulated in the body . Obesity is due to increased
energy intake exceeding the energy expenditure . The excess energy
stored in adipose tissue as fat.It is assessed by obesity index.
•Obesity Index (Belgian mathematician Quad let) is used to assess the
obesity.
Calculation of obesity Index: W / H
2
(where W= Body weight in kg and
H= height in meters)
Grading of Obesity based on obesity index
( W/H
2
)
Grade Obesity Index
3 >35
2 30-35
1 25-29.9
0( non obese) 20-24.9

4. Body mass index(BMI)
•Body mass index(BMI)is the modern expression of an old terminology
“Obesity Index”. It is the most widely used marker for obesity. It is 24
hours urinary creatinine excretion .
•Obese men : BMI > 27.8 kg /m
2
•Obese

women
:
BMI > 27.3 kg/m
2
Types of Obesity:
Central

obesity in males : Android / apple type(abdominal in males)
Central

obesity in female: Gyneoid Type(around breast ,hips and thighs
in females)
Increased waist to hip ratio (abdominal obesity) indicates a greater risk
of Coronary heart disease (CHD).
excess of 120%desirable body weight

5. Relationship between body mass index (BMI) and
degree of obesity
Value of BMI Degree of obesity
20-24.9 Normal
25-29.9 Grade I
30-35 Grade II
> 35 Grade III

6. •Metabolic :Overeating : Ingestion of food in excess of body’s need.Intake of
calorie rich food in excess amount and lack of exercise. Deficiency of the
enzyme ATP ase which impairs normal energy metabolism and gain more body
weight.
•upper body fat deposition : mainly by hypertrophy (Increase in size of existing
cells of adipose tissue).
•lower body fat deposition : mainly by Hyperplasia (Increase in number of
adipocytes of adipose tissue).
•Genetic predisposition : if one parent obese, 50% chances children becoming
obese.No gene alone is responsible for the production of obesity.
•Genetic causes of obesity : mutation in Leptin and Leptin receptors in
hypothalamus(Neuropeptide Y). Neuropeptide Y increase desire for
carbohydrates.
•Environmental factors: the relative abundance and type of food
•Social factors
Primary causes of obesity

7. Secondary causes of obesity
A. Endocrine factors:Obesity may result from endocrine disorders like
1.Hypothyroidism(due to decreased energy requirements)
2.Hypopituitarism
3.Hypothalamic syndrome
4.Cushing’s syndrome
5.Hypogonadism
6.Diabetes Mellitus( Decrease in number of Insulin receptors in adipose tissue cells
and Serum insulin level . The sensitivity of peripheral tissue for insulin is
decreased with substantial increased cardiovascular risk).
7.Insulinoma (due to increased energy intake as a result of hypoglycaemia)
8.Obesity in women : Puberty , pregnancy ,after menopause
B. Drug therapy

8. Metabolic syndrome and Obesity
Metabolic syndrome (Syndrome X) is associated with :
insulin resistance
Hyperglycaemia
Hyperlipedemia
(increased serum LDL level and decreased serum HDL)
OBESITY

9. Obesity as a health risk
An obese person has higher the risk of :
•Impaired glucose tolerance(Insulin resistant Diabetes Mellitus)
•Fasting hyperlipidemia [ Elevated cholesterol levels, Atherosclerosis,
Hypertension , Coronary Heart disease(CHD) ,Stroke, Metabolic syndrome]
•Predisposition to
A. Osteoarthritis
B. Thromboembolism
C. Cholelithiasis
D. Hypoventilation
E. Hypoxemia
F.Cancer
Morbidity and Mortality (reduced life-span)due to cardiovascular complications.
Calorie-fat-restricted diet
may retard aging process , reduce obesity
and extend life-span.

10. Adipose tissue talks to brain through Factors
•Leptin
•Neuropeptide-Y
•Ghrelin
•Gallatin
•Adiponectin
•Visfatin
•Omentin
•Tumor necrosis factor- alpha
•Resistin
•Retinol-binding protein 4

11. Fat talk to brain through Leptin
•Fat depot full appetite decreased
•Galanin: craving for fatty food
•Leptin improves insulin sensitivity in muscle as well as liver.
•Obesity is associated with leptin resistance and high levels of
plasma leptin.
• Genetic causes of obesity : mutation in Leptin(Lep gene) and
Leptin receptors in hypothalamus leads to removal of this
feedback mechanism, so uncontrolled eating and obesity are the
results.
•Neuropeptide-Y : increases desire for carbohydrates.

12. Leptin as a control mechanism of obesity
•Leptin (Greek word Leptos = thin):
1.is a peptide hormone (16kDa protein with 167 amino acids)produced by white
adipose tissue and to some extent by gastric mucosal cells. It is secreted by
adipocytes.
2.is an index of energy reserve in the human body.
3.levels lowered on fasting or following a very low calorie diet(VLCD).
4.is a product of “Lep”gene located on chromosome on 7 in human (“ob”gene
in mice). Leptin leads to suppression of food intake.
5.production or response failure in grossly obese human .
“Lep ”gene mutation or mutation of its receptor in hypothalamus leads to
removal of feedback mechanism. So uncontrolled eating and obesity results.
Administration of recombinant leptin is found to be effective in control of
childhood obesity.

13. Functions of Leptin
1.plays a role is regulating energy intake & energy expenditure ,including appetite
and metabolism.
2.functions as a satiety signal. It signals the brain that enough energy has been
stored and that intake of food is no longer necessary . It would suppress further
food intake.When the energy reserve is adequate , the adipocytes produce
increased amount of leptin which is released into blood.
3.secretion is stimulated when there is enough fat deposit (signalling excess
energy storage).
4.Adipoinsular axis : with insulin promoting leptin secretion and leptin inhibiting
insulin release . It inhibits proinsulin biosynthesis as well as insulin secretion
(thus reduces insulin level).
5.reduces intracellular triglyceride levels.
6.inhibits neuropeptide-Y secretion . So when fat depots are full ,appetite is
decreased and this decreases desire for carbohydrates.
7.administration inhibits gastric ulcer formation in rats and stimulates oesophageal
adenocarcinoma cells.

14. Neuropeptide-Y and obesity
•Neuropeptide-Y is:
1.a polypeptide
2.secreted by hypothalamus and small intestine (ileum) N cells.
3.present in entire nervous system,adrenal gland and pancreas.
4.Functions of Neuropeptide Y: inhibits insulin secretion and
stimulates desire for carbohydrates (responsible for obesity).

15. Gherlin and obesity
•Biochemistry of Gherlin : a polypeptide with 28 amino
acids, in which fatty acids are incorporated(acylated on
Serine 3 with n-Octanoic acid).
•secretion of Gherlin : secreted mainly by adipocytes and
also by P/D1 cells lining of fundus of human stomach and
epsilon cells of pancreas.
•Ghrelin levels increase before meals and decrease after
meals.

16. Functions of Gherlin
A.stimulates hunger and appetite by acting on the hypothalamus.
B.Plasma Gherlin is increased in fasting state(before meal) which
produces hunger signals . It increases before meals and decreases
after meals.
C.stimulates NPV release.
D.stimulates gastric secretion.
E.emptying insulin secretion.
F.increases growth hormone secretion.
G.activate the endothelial isoform of nitric oxide synthase.
H.is essential for cognitive adaptation to changing environments and in
process of learning in the hippocampus.

17. Galanin and obesity
•Galanin :a neuropeptide which increases the craving for
fatty foods.

18. Adiponectin and obesity
•an adipokine( 224 amino acids containing peptide acylated on Serine
3 with n-Octanoic acid) and produced exclusively by adipose tissue.
•Plasma level of Adiponectin is inversely correlated with body fat
percentage.
•Plasma level of Adiponectin is parallel with serum HDL level. Low
levels of Adiponectin and HDL are seen in metabolic syndrome and
Diabetes mellitus.
•Decreased adiponectin is associated with polycystic ovarian
syndrome (PCOS) independent of body mass index.
•Thiazolidine drugs have been found to increase the adiponectin levels
that can modify the sensitivity of target cells to insulin.
•Lectin : Adiponectin ratio higher in subjects with metabolic syndrome
(MS) than in individual without (MS).

19. Functions of Adiponectin
•has pronounced effects on the metabolism of carbohydrates and
lipids in liver and muscles.
•promotes the uptake and oxidation of fatty acids by myocytes . It
blocks synthesis of fatty acids and gluconeogenesis by
hepatocytes.
•favours uptake and metabolism of glucose by muscle and liver.
The effects are exerted through an AMP mediated kinase (AMPK)
that can phosphorylate several target proteins thus affecting
metabolic pathways . Net effect is to increase the sensitivity to
insulin ,to promote fatty oxidation and improving the glucose
tolerance.
•plays a role in the suppression of the metabolic dearrangements
that may result in type 2 Diabetes mellitus, obesity ,
atherosclerosis and non-alcoholic fatty liver disease (NAFLD).

20. Visfatin and obesity
Visfatin = pre -B-cell colony enhancing factor(PBEF)
secretion of Visfatin: mainly by adipocytes
Function of Visfatin : glucose uptake mediated by direct
binding and activation of insulin receptor (lipogenic effect
hence obesity).It doesn’t promote the insulin resistance.

21. Omentin and obesity
Omentin :
•Biochemistry : a peptide
•synthesis : stromal -vascular cells within the adipose
tissue rather than by adipocytes.
•Secretion : predominantly by visceral fat
• Functions: positive effects on glucose uptake and works
as an insulin sensitiser.

22. Tumor necrosis factor-alpha and obesity
Tumor necrosis factor-alpha:
•Secretion : macrophages have been implicated in TNF
production from adipose tissue and not derived from
adipocytes.
•Function: reduces insulin action. Its levels are elevated
in obesity and in insulin-resistant state.

23. Resistin and obesity
Resistin:
• is a small inflammatory molecule .
• is the product of macrophages within the fat depot and is
not synthesised by adipocytes.
•Functions:
1.Hyperglycaemic effect / action.
2.increases hepatic glucose output .

24. Retinol-binding protein 4(RBP4) and obesity
•Function of Retinol-binding protein 4(RBP4) : over
expression of RBP4 impairs hepatic and muscle insulin
action.
•High serum RBP4 levels associated with insulin resistance
in obese human and those with type 2 diabetes.

25. Non-esterified fatty acids(NEFAs) and obesity
Non-esterified fatty acids ( NEFAs):
•Secretion : NEFA is primarily released from adipose
tissue during fasting.
•Functions : reduce uptake of glucose by adipocytes and
muscles . They promote hepatic glucose output.The net
effect is to promote lipid burning as a fuel source in most
tissues , while sparing carbohydrate for neurones.
•Lipolysis in adipocytes is repressed by insulin. Insulin
resistance from any cause can lead to NEFA elevation ,
which in turn induces additional insulin resistance as part
of a vicious cycle.

26. Inflammation in obesity
•Obesity and type 2 diabetes are inflammatory states,
consistent with the production of pro-inflammatory cytokines
such as TNF and IL-6 by adipose tissue.
•In obese ,bone-macrophages are recruited to adipose tissue ,
under the influence of proteins secreted by adipocytes, which
includes macrophage chemoattractant protein-1(MCP-1).
•Intra-adipose macrophages are dominant contributors to the
insulin resistance that is associated with obesity.
•Thiazolidinediones , which are PPAR -alpha agonists used
clinically as insulin sensitisers, reduce MCP-1levels and
macrophage infiltration in adipose tissue.

27. Sleep and obesity
•Less sleep can cause increased hunger ,appetite and body
weight.
•For children and adult,hours of sleep per night is inversely
related to BMI.
•Sleep deprivation produces decreased leptin secretion,
increased ghrelin levels and decreased glucose tolerance.
•Average amount of sleep has steadily decreased among
adults and children during the past several decades , all
over the world , along with increase in incidence of obesity.

28. Diseases related to obesity
•The major ill effects of obesity are increased risk of: coronary artery
disease:
A.Diabetes Mellitus
B.Hypertension
C.Metabolic syndrome(Syndrome -X)
Consequences of metabolic syndrome :
insulin resistance
hyperglycaemia
Hyperlipidemia (increased LDL, AND decreased HDL)
Obesity

29. Pathological changes in obesity
•Obesity is associated with increased adipose stores in
the subcutaneous tissue ,skeletal muscles, internal
organs such as kidney , heart and liver.
•There is increase in size both size (hypertrophy) and
number of adipocytes (hyperplasia).
•The presence of excessive numbers of adipocytes
signals the body to synthesise more triglycerides ,so
that can they can be filled leading ultimately to an
excess of total stored fat in the body.

30. Management of obesity
•Life style modification (for management of obesity,it is the best remedy) :
1.reduce intake of calories (energy restriction) and fat: by reducing carbohydrate
in diet to 50-100 g/day,by restriction on sugar ,sweets chocolates and cakes.
2.frequent small meals with lots of vegetables make the food palatable(giving
feeling of satiety)
3.Weight monitoring (every two weeks) and weight reduction by energy
restriction
4.controlled exercise (reduce weight and maintain reduced weight)
•Jejunoileal bypass surgery or gastroplasty to delay gastric emptying in patients
who have failed weight loss regimens and who are 50-100% of ideal body
weight excess.
•Calorie -fat -restricted diet may retard aging process and extend the life-span.
•Drugs given higher grade obesity: Endocannabinoid receptor antagonists
decrease appetite thus will reduce the intake of food.

31. Dietary restriction as a treatment of obesity
•Weight loss by increasing physical exercise (increased
energy expenditure).
•Decreased energy input below energy expenditure.
•increased consumption of non-nutritive cellulose
substances . Dietary fibres distends the stomach and
thereby partially satisfies hunger.

32. Atkins Diet for obesity( Dieting)
Dieting for obesity: aim at a negative calorie balance.
Atkin’s diet (proposed by Robert Atkins):Low carbohydrate, ketogenic,
high protein diet for losing weight of obese people. This high fat diet
reduces appetite and thus food intake.
20g of carbohydrate per day (against normal desirable intake is 100
-120g/day) but unlimited consumption of fat and protein are permitted
(<10% of 2000 kcal/day) in Atkin’s diet.
When such a diet consumed , the liver will be predominantly
glucogenic and ketogenic . ATP is provided by oxidation of fatty acids.
Peripheral tissues will utilise the excess ketone bodies for their
energy needs.The substrate for gluconeogenesis is mainly glucogenic
amino acids.
Insulin secretion as well as the increment in glucose in the post
prandial state is low.

33. Limitations of Atkins Diet for obesity( Dieting)
This low carbohydrate diet was found to give
promising results in 6-12 weeks trials compared to low
calorie and low fat diets.
However ,long term human consumption of Atkin’s diet
is controversial. Consuming less food or consuming a
low fat diet will not have desired effects, as the body
will have tendency to switch to the fasting metabolic
profile soon after meals.
More long-term trials are necessary to prove the
efficacy of the low carbohydrate ketogenic diet.

34. Drug therapy for Obesity
•The use of drugs in treating obesity has met with varying success.
Most drugs have undesirable side effects.e.g.
drug therapy for
obesity
Mechanism of action of
drug for reducing obesity
Side effects of drug therapy
Amphetamine increase BMR
addictive and cause
psychological problems.
Fenfluramine produce feeling of satiety
nausea , diarrhoea,
occasionally depression
during use and upon
withdrawal
Thyroxine increase BMR
body protein loss and bone
demineralization
Dinitrophenol(DNP)
an uncoupler of oxidative
phosphorylation
toxic side-effects
Leptin and Glucagon
like peptide -1 (GLP-1)
activate satiety signal

35. Surgical treatment of Obesity
Lipectomy
Liposuction}
have been used in extreme cases of obesity.

36. Obesity and Regulators of appetite
•Hypothalamus has the central control of appetite.
•Factors involved in control of appetite:
1.psychological
2.genetic
3.Neural
4.Humoral factors
Melanocyte stimulating hormone(MSH):powerful appetite suppressant
A.Prader Willi syndrome (deletion of part of chromosome 15)
B.Laurence-Moon-Biedl ( a genetic defect)
patients
overeat
and
therefore
obese
}

37. Polypeptides those increase appetite and obesity
•Neuropeptide Y (NPY)
•Gherlin
•Melanin concentrating hormone(MCH)
•Orexin
•Endocannabinoid
•Cholecystokinin(CCK)
•Polypeptide YY(PYY)
•Insulin
•Cortisol

38. Polypeptides those decrease appetite
•Leptin
•Melanocyte stimulating hormone(MSH)
•Glucagon related peptide I(GLPI)
•Cocaine amphetamine related transcript (CART)
•Serotonin

39. Nutritional Management of hypercholesterolemia
1.Consumption of PUFA:(cotton seed oil, soybean oil, sunflower oil , corn oil , fish
oil): help in transport of cholesterol by LCAT mechanism and its excretion from
body.
2.Dietary Cholesterol intake:<300 mg/day. Avoid cholesterol -rich food.Drug
Ezetimide inhibit intestinal absorption of dietary cholesterol and thereby reduce
plasma cholesterol levels.
3.Plant sterol and their esters(e. g. sitostanol esters) : inhibit intestinal absorption of
dietary cholesterol and thereby reduce plasma cholesterol levels.
4.Dietary fibres : Fibres present in vegetable reduce intestinal absorption of dietary
cholesterol and thereby reduce plasma cholesterol levels.
5.Avoiding high carbohydrate diets(avoid sucrose).
6.Curtail/moderate alcohol consumption: beneficial effects of moderate alcohol
intake are masked by ill effects chronic alcoholism.Red wine has beneficial effects
due to its antioxidants and low alcohol contents.
•use of drugs: statins (lovastatin , simvastatin, fluvastatin ,atovastin , pravastatin)
inhibit HMG CoA reductase , cholesterol biosynthesis and hence reduce plasma
cholesterol levels.

40. Management of Hyperlipoproteinemia
•Restriction of fat intake
•increase supplementation of PUFA
•Low cholesterol diet
•Decrease intake of saturated fat
•supplementation of bile binding resins
•restrict carbohydrate diet
•supplementation with MCT
•Clofibrate

41. Management of gall stones
•Oral administration of bile acids e.g. Chenodeoxycholic
acid, Urodeoxycholic acid to dissolve gall stone & to
reduce relative saturation of bile with cholesterol.Shock
wave lithotripsy to shatter gall stones to tiny fragments to
enable passage through cystic tract.
•Cholecystectomy (surgical removal of gall bladder)

42. Anorexia nervosa
Anorexia nervosa: is an eating disorder seen predominantly in young women
who develop a fear of becoming fat.
Characteristics of Anorexia nervosa:
1.Restriction of food intake
2.Markedly decreased body weight , undetectable body fat
3.Skin changes such as hirsutism , dryness and carotenemia.
4.Hypoalbuminemia and oedema
5.Anemia
6.Amenorrhea due to low basal levels of Luteinizing hormone(LH) and
Follicle stimulating hormone(FSH).
7.Leukopenia
8.Hypokalemia
9.Cardiovascular changes such as bradycardia , hypotension and
arrhythmias
10.Parotid gland enlargement
11.Hypothermia

43. Characteristic feature of Bulimia
•Bulimia: is an eating disorder seen predominantly in young women
who develop a fear of becoming fat.
•Characteristic of Bulimia :
A.by episodes binge eating ,followed by self -induced vomiting.
B.the body weight is near normal.
C.amenorrhea is frequent.
D.metabolic alkalosis and hypokalemia.
E.cardiovascular and skin changes are uncommon(unlike anorexia
nervosa).

44. Thank You