CHLOROGENIC ACID (CGA) belongs to the super family Caffeoylic Acid is gaining lot of media attention due to its anti-potential property. The word “Chloro" derived from Greek (light green) and Genic means "giving rise to”. You will get the information related to the anti-obesity phytochemical (CGA) and its mechanism in managing obesity

1. 1
Dr. Sudharani, N.
Assistant Professor
(Food Science and Nutrition)
College of Horticulture
Mudigere, Karnataka-577132

2. Topic division
Introduction
Reviews
Summary
Conclusion
References
2

3. Glossary
• CGA- Chlorogenic Acid
• GCBE- Green Coffee Bean Extract
• LDL- Low Density Lipo Protein
• HDL- High Density Lipo Protein
• WHR- Waist to Hip ratio
• BMI- Body Mass Index
• FBS- Fasting Blood Sugar
• OGTT- Oral Glucose Tolerance Test
• SREBP- Sterol Regulatory Element Binding Protein
• BAT- Brown Adipose Tissue
• WAT- White Adipose Tissue
• GADPH- Glyceraldehyde 3 –phosphate dehydrogenase
• PPAR- Peroxisome Proliferation Activator Receptor
• HMGR- 3 Hydroxyl-3- Methylglutaryl co-enzyme A reductase
• ACAT- Acyl-CoA cholesterol Acyltransferase
• CYP7A1- Cytochrome P450 family 7 Subfamily A Member 1 Enzyme
• CYP51- Cytochrome P450 family 5 member1 Enzyme
• ACC- Acetyl Co A Carboxylase
• AMPK- Adenosine Monophosphate Protein Kinase 3

4. 4
Phenotypic manifestation of abnormal or
excessive fat accumulation that alters health and
increases mortality.
WHO, (1998)
Intake
Expenditure
Obesity

5. BMI>18.5-24.9 = Normal
BMI> 25-29.9= Overweight
BMI >30 Obese
5
How do you know that you are Obese?
Kelly et al., 2015

6. 6
Types of Obesity-
Are you an Apple or a Pear??
Excess fat on abdomen
Common in Men
Apple / Android Pear / Gynoid
Excess fat on thighs and buttocks
Common in Women
Kelly et al., 2015

7. 7
LANCET, 2014
World Obesity Prevalence rate

8. 8NHFS:2013
INDIAN SCENARIO OF OBESITY

9. 9
Socio cultural
determinants
Biological
determinant
Behavioral
determinants
Causes of
Obesity
•Smoking
•Alcohol consumption
• Heredity
• Pregnancy
• Age
• Pre and post menopausal
• Socio economic status
Molly et al., 2018

10. Complications of Obesity
10Molly et al., 2018

11. 11
Muhammad et al., 2018

12. 12
cJun –N- terminal- kinase (JNK) Muhammad et al., 2018

13. TREATMENTS
 Dietary changes
 Behavioral changes
 Exercise
 Weight-loss surgery
 Medication
13
Molly et al., 2018

14. 14
Orlistat (Xenical)
Met formin (Gucophage)
Lorcaserin (Belviq)
Liraglutide (Saxenda )
Phentermine-topiramate (Qsymia)
Phentermine (Adipex-P, Suprenza)
Bupropion and Naltrexone (Contrave)
Fenfluramine (Pondimin)
Sibutramine (Meridia)
The General Anti-obesity medications
Randall et al., 2003
FDA, 1994
Cost: Rs. 43000/- to 52000/- (30 capsules )

15. Phytochemical
 Greek: “Phyton” - ‘plant’
 Chemical compounds produced by plants, generally to help them
protect against competitors, predators, or pathogens.
 Fruits, vegetables, grains, beans, and other plants.
 Some of these phytochemicals are believed to protect cells from
several disease.
 Anti-inflammatory, Anti-diabetic and Antiobesity etc..
15
Ginger, Turmeric, Cinnamon, Aloe vera, Cabbage, Amla, Garlic, Chilli,
Pepper, watermelon, Avacado, Curry leaves, GLV’s, tomatoes etc.....
Chandrasekaran et al., 2012

16. 16
How the Phytochemicals generally targets Obesity?
Reduction in adipose tissue mass by inhibition of precursor cell
proliferation.
Enhancing apoptosis of fat cells.
 Hindering the absorption of triglyceride by reducing formation of
pancreatic lipase.

17. CHLOROGENIC ACID
Derivatives
 Caffeic acid
 Quinic acid
 Ferulic acid
 Coumaric acid
 Hydroxy Cinnamic acid
17
“Chloro" -Greek (light green) and Genic means "giving rise to”
Green color produced when Chlorogenic acids are oxidized.
Caffeoylic Acid

18. 18
Distribution of Chlorogenic acid in various foods
Source Chlorogenic acid (%)
Coffee bean (Green) 12-14.0
Coffee bean (roasted) 3- 4.0
Blue berry 1.6-2.0
Apple 1.5-1.8
Sunflower 1.0- 1.2
Bell pepper 0.3-1.0
Bamboo leaves 0.6-0.9
Sweet potato 0.3-0.7
Pear 0.3-0.5
Plums 0.4
Cherries 0.3
Hibiscus 0.3
Tomato 0.1
Ernest, S., 2013 18
0.1- 2%

19. 19
14%
4%

20. Coffee
Family: Rubiaceae
Scientific name: Coffea arabica
Native: Ethiopia
20
World production: 78 lakh tones (Area: 10.44mHa)
Indian production: 2.75 lakh tones (Area: 3.47 lakh Ha)
Productivity- 793kg/Ha
CCRI, 2015

21. Difference??
COFFEE
• Matured
• Ripen
• Roasting
• Processing
Dry and Wet
method
• High Caffeine
• Low CGA
GREEN COFFEE
• Matured
• Un Ripen
• Unroasted
• Processing
Dry method
 Low Caffeine
 High CGA
21

22. Processing of Green coffee
22
CCRI

23. Functions
of CGA
23
Muhammad et al., 2018

24. Determination of CGA
• Gas chromatography
• HPLC
• UHPLC
• Spectrometry
• Ultra sonic Extraction
24

25. Side effects of CGA
• Higher Homocysteine levels
25
Caffeine:
Strong coffee: 95mg (Robusta)
Light coffee: 63mg (Arabica)
Decaffeinated coffee: <2mg
Green coffee: 3-4 mg
Mullen et al., 2011Mullen et al., 2011

26. 26
B. CGA levels in coffee fruit samplesA. Caffeine levels in coffee fruit samples
a. Dry c. Hot air oven (120° C)
b. Wet d. Deep freeze (-12 ° C)
Mullen et al., 2011
Fig. 1. Effect of Processing on Caffeine and CGA content Coffee fruits

27. Green coffee brands available in market
27
Beans: (200mg) 300-350/-
Instant Powder: (75g) 25 sachet (3g each)- 750-800/-
Capsules (90 no. and ): 800-850/-
Flakes : (100g): 250- 320/-

28. How to consume Green Coffee ????
28

29. 29

30. Anti-diabetic and anti-lipidemic effects of
Chlorogenic acid
To investigate the effect of CGA on glucose tolerance and
lipid metabolism before and after 2-week treatment in mice.
Objective:
30
Khang et al., 2016
Biochemical Pharmacology

31. Material and Methods
31
Two weeks
Mice (National University of Singapore): 5 groups :(n=4)
1. Lean
2. Dc (Diabetic control)
3. 250mg/kg CGA
4. 250mg/kg CGA+ Compound ‘C’
5. 250mg/kg Metformin
OGTT- before treatment and 10 min 20, 30, 40 , 50 … upto 120min after
treatment
Reassigned randomly (n=4) and
treated with 250mg CGA and Metformin /kg daily.
AMPK activity was measured
One week rest to clear the acute effects of various treatments
After 2 weeks: body weight and food intake was measured

32. 32
Fig. 1. Effects of CGA on glucose tolerance and inhibitory effect of compound c in mice
A
B
A

33. 33
Table 1: Body weight and food intake in 2-week treatment of mice with CGA
and Metformin
Treatment Body weight (g) Food intake (g/kg)
Day 1 Day 14 Day 1 Day 14
Lean 21.5 22.5 0.55 0.60
DC 51.5 53.5 0.66 0.81
Metformin 53.25 50.25 0.63 0.74
CGA 50.75 44.75 0.69 0.73
Dc (Diabetic control)

34. 34
Fig. 2. CGA ameliorates Hepatic lipid accumulation by inhibition of Fatty acid
synthesis

35. Fig. 3. CGA administration on Phosphorylation of AMPK and ACC in mice
AMPK- Adenosine Monophosphate Protein KinaseACC- Acetyl Co A Carboxylase
35
C

36. 36
Fig. 4. CGA ameliorates hepatic lipid accumulation by inhibition of fatty acid synthesis

37. AMPK
37
CGA
Adiponectin
AMPK Phosphorylation
ACC
Muscle glucose transport Gluconeogenesis Fatty acid synthesis
Fasting glucose, glucose tolerance, Insulin Sensitivity
Triglyceride, & Cholesterol, Hepatic Steatosis
GLUT4
G6pase

38. Conclusion
• Administration of CGA inhibited hepatic G6Pase expression and
activity, reduces hepatic steatosis, improved lipid profiles and
skeletal muscle glucose uptake by increasing the GLUT 4
expression in the muscle.
• CGA up regulates AMPK (Adenosine Monophosphate Protein
Kinase) pathway by reducing ACC and Glucose 6 phosphate
enzyme and enhances insulin sensitivity.
38

39. To investigate the effects of high cholesterol diet in rats
with or without the supplementation of Chlorogenic acid.
Chlorogenic acid exhibits cholesterol lowering and fatty liver
attenuating properties in hypercholesterolemic rats induced
with a high-cholesterol diet.
Chun et al., 2012
Phytotherapy Research
Objective:
39

40. Material and Methods
40
for 28 days
Animals sacrificed: Blood samples and liver tissues
2 month old male rats
Control group (Standard chow diet)
HCD (1% Cholic acid, 2% pure cholesterol & 5.5% Canola oil)
Chlorogenic acid –Low :CA-L (1mg/kg/day)
Chlorogenic acid –High: CA-H (10mg/kg/day)
4 groups (n=10)
Atherogenic index Cardiac risk factors Lipid profile

41. Table 1. Plasma lipid levels of rats in the Control, HCD, CA-L and
CA-H groups
41
Animal group Control HCD CA-L CA-H
Total cholesterol
(mmol/L)
Before 1.89 2.26 2.49 2.29
After 1.76 5.70 5.78 4.83
Triglyceride
(mmol/L)
Before 0.71 0.70 0.73 0.73
After 0.71 0.70 0.73 0.73
LDL
(mmol/L)
Before 0.69 0.83 0.85 0.95
After 0.40 9.91 8.74 6.93
HDL
(mmol/L)
Before 0.95 1.08 1.12 1.10
After 0.90 0.44 0.81 0.96
CA-L (1mg/kg/day) CA-H(10mg/kg/day)
NS

42. 42
Fig.1. The Atherogenic index and Cardiac risk factors of experimental animals
AGI= Total serum cholesterol- HDL/ HDL
CRF= Total serum cholesterol/ HDL

43. Fig .2. Gene expressions of HMGR, CYP51, ACAT, CYP7A1 and PPAR- α in
isolated livers. 43
GADPH- Glyceraldehyde 3 –phosphate dehydrogenase
PPAR- Peroxisome Proliferation Activator Receptor
HMGR- 3 Hydroxyl-3- Methylglutaryl co-enzyme A reductase
ACAT- Acyl-CoA cholesterol Acyltransferase
CYP7A1- Cytochrome P450 family 7 Subfamily A Member 1
CYP51- Cytochrome P450 family 5 member1 Enzyme

44. (A) The gross appearance of the entire liver
Fig. 3. Effect of Chlorogenic acid on the appearance and lipid contents of liver
(B) Total lipid content per gram of liver
44

45. Mechanism of PPAR
45

46. Conclusion
 CGA-significantly reduced the total cholesterol and LDL, but
alleviating HDL in hypercholesterolemic rats.
 Hypocholesterolemic effect of CGA leads to Atheroscleroprotective,
Cardioprotective and Hepatoprotective acticity by increasing the
Adiponectin and Fat oxidation.
 The Hypocholesterolemic effect of CGA are probably due to the
increase in fatty acids utilization in liver through the up regulation of
PPAR (Peroxisome proliferation Activator Receptor) gene expression.
46

47. Stimulation of postprandial fat utilization in healthy humans
by daily consumption of Chlorogenic acids.
To study the effect of CGA consumption on
energy expenditure in humans.
47
Objective
Satoko et al., 2013
Biosci. Biotech. & Biochem.

48. Material and Methods
48
Ethical committee approval
Written consent : 18 healthy male (Age 36 ±7) 2 groups (n=9)
Control group: (0 mg CGA /185 ml)
Test group: (329 mg/ 185 ml)
Instructed to consume 185ml in 2 intervals/ day
After 4 weeks the energy metabolism
Height, body weight and body fat ratio
Can
4 weeks
Same meal:
2500kcal/d

49. 49
Table 1. Composition of the Test Beverage
CGA beverage Control beverage
CGA (mg/can) 329 0
Caffeine (mg/can) 50 51
Nutritional facts
Energy (kcal/can) 20 22
Protein (g/can) 1.1 0.7
Fat (g/can) 0.6 0.4
Carbohydrates (g/can) 2.6 3.9
Total volume(ml/can) 185 185

50. 50
Table 2. Changes in Anthropometric variables and Blood glucose
Initial 4 weeks
Body weight (kg)
Control group 66.4 66.4
CGA group 66.2 66.2
BMI(kg/m2)
Control group 22.0 22.0
CGA group 21.9 22.0
Body fat ratio (%)
Control group 16.9 16.7
CGA group 16.6 16.7
Glucose (ml/dL)
Control group 104.6 97.8
CGA group 107.6 99.0
NS
NS
NS
6.8
8.6

51. 51
Fig. 1. Changes in the Energy Expenditure in control and test group

52. 52
Table 3. Average Carbohydrate and Fat Utilization
Initial 4 weeks
Carbohydrate utilization (mg/min/kg)
Control group 2.56 2.55
CGA group 2.60 2.59
Fat utilization (mg/min/kg)
Control group 0.914 0.912
CGA group 0.903 0.958
NS

53. SREBP Mechanism
Cholesterol synthesis: >30gene
Adiponectin: Regulate glucose, Fat oxidation, Ghrelin
AMPK Phosphorylation
HMGR- 3 Hydroxyl-3- Methyl glutaryl reductase
Cholesterol, Liver Steatosis and Insulin resistance
53
Sterol Regulatory Element Binding Protein

54. Conclusion
 Beverage containing CGA lead to a significant increase in the
postprandial fat utilization and energy expenditure of healthy
individuals.
 These effects are mediated by the suppression of SREBP (Sterol
Regulatory Element Binding Protein) gene, which regulates the
Cholesterol synthesis in the liver.
 CGA proves to decrease the HMGR- 3 Hydroxyl-3- Methylglutaryl co-
enzyme A reductase and thus in turn reduces the storage of excess fat
by increasing the Insulin sensitivity.
54

55. 55
Effects of ingestion of Chlorogenic acids on sleep architecture
and energy metabolism : a randomized, placebo-controlled,
double-blinded cross-over trial
To determine the effects of CGA ingestion over 5
days on energy metabolism and sleep quality in humans.
Objective
Insung et al., 2017
Bri. J. of Nutri.

56. Material and Methods
56
9 healthy subjects (4 male and 5 female) (Age25year)
Placebo control (n=4)
Test beverage containing 600 mg of CGA for 5 days
On the fifth night, subjects stayed in a whole-room metabolic chamber
to measure energy metabolism
Evaluated the sleep by using Polysomnographic recording
100ml CGA was consumed 10 min before bed time
Subjects ingested specified meals for breakfast, lunch and dinner
15 E% protein, 25 E% fat and 60 E% carbohydrates
Energy distribution was 30 E% for breakfast, 30 E% for lunch and 40 E% for dinner

57. 57

58. 58
Table 1. Anthropometric variables before and after ingestion of CGA and
placebo beverage
Initial After 5 days
Body weight (kg)
Placebo group 63.90 64.00
CGA group 62.90 63.30
BMI (kg/m2)
Placebo group 21.80 22.10
CGA group 21.70 21.90
Body fat (%)
Placebo group 24.60 25.10
CGA group 23.80 24.60

59. 59
Table 2. Sleep Architecture
Parameters Control CGA
Total bedtime (min) 480.00 480.00
Total sleep time (min) 436.00 444.20
Wakefulness (min) 27.90 26.70
Sleep latency (min) 15.60 08.70
Sleep efficiency (%) 90.90 92.50
Stage 1 (min) 58.40 56.70
Stage 2 (min) 274.10 279.80
SWS (min) 15.70 19.20
REM sleep (min) 87.80 88.30
8hr
44min
14 min
94min
4.4hr
32 min
1.47hr
1.54hr
7.4hr

60. 60
Fig. 1. Sympathetic (a) and Parasympathetic (b) nervous system activities
during calorimetry after 5 d of ingestion of the chlorogenic acids and placebo beverage
Chlorogenic acids beverage (●)
Placebo beverage (○)

61. 61
Fig. 2. Energy expenditure and substrate oxidation during sleep after 5 d of
ingestion of the chlorogenic acids and placebo beverage.
Chlorogenic acids beverage (■)
Placebo beverage (□)
Energy metabolism was measured for 16 h (from 3 h before
bedtime on the 5th day to 5 h after waking the next morning)

62. 62
Consumption of CGA significantly increased the fat
oxidation during sleep.
Ingestion of CGA proved to increase parasympathetic
activity during sleep.
CGA stimulated fat oxidation without an adverse effect
on sleep architecture; rather, it shortened sleep latency.
Conclusion

63. Fatemeh et al., 2017
Asia. Pac. J. Clin. Nutr.
63
Energy restriction combined with Green coffee bean extract affects
serum adipocytokines and the body composition in obese women
To evaluate the efficacy of green coffee bean extract combined with
an energy-restricted diet on the body composition and serum adipocytokines
in obese women.
Objective

64. Material and Methods
64
8 weeks
64 obese women (20–45 years )
2 groups
Intervention group (400 mg GCBE capsule)
Control group (Placebo 400mg of Starch)
All participants were on an energy-restricted diet
Body composition, Leptin, Adiponectin, Lipid profile,
Free fatty acids (FFAs) and fasting blood sugar
25% Energy restriction
15% Protein
55% CHO
30% Fat

65. 65
Table 1. Anthropometric characteristics of the study population
Parameters Placebo group Green coffee group
Weight (kg)
Week 0 12.43 11.98
Week 8 12.16 10.40
BMI (kg/m2)
Week 0 4.96 4.37
Week 8 4.84 3.89
Fat mass (kg)
Week 0 4.07 4.27
Week 8 4.74 3.75
FMI (kg/m2)
Week 0 3.69 3.23
Week 8 3.23 3.23
WHR
Week 0 0.20 0.08
Week 8 0.04 0.02
Visceral fat
Week 0 0.50 0.30
Week 8 0.33 0.13
NS

66. 66
Table 2. Effect of GCBE on FBS, Fasting insulin and lipid profile in the study population
Parameters Placebo group Green coffee group
FBS (mg/dL)
Week 0 5.63 5.83
Week 8 5.08 5.56
Fasting Insulin(µm/mL)
Week 0 0.71 0.68
Week 8 0.70 0.67
Total cholesterol (mg/dL)
Week 0 13.50 14.06
Week 8 12.58 10.53
LDL (mg/dL)
Week 0 9.24 10.71
Week 8 7.79 03.62
HDL (mg/dL)
Week 0 1.47 1.61
Week 8 1.02 1.45
TG (mg/dL)
Week 0 26.52 33.99
Week 8 25.73 31.25

67. 67
Table 3. Effect of Green coffee bean extract on Leptin and Adiponectin
Variable Placebo group Green coffee group
Leptin (ng/mL)
Week 0 9.05 8.06
Week 8 7.32 8.31
Adiponectin(µg/mL)
Week 0 1.05 1.07
Week 8 2.03 1.03

68. Conclusion
 Energy restriction combined with GCBE may effectively reduce the
BMI, FMI, total cholesterol and LDL and also alter serum
adipocytokines.
 The presence of Chlorogenic acid in green coffee bean extract reduced
the weight effectively in obese people.
68

69. 69
Abdulrahim , 2017
J.of Chem. & Pharma. Res.
Objective
Effect of Orlistat Drug and Green Coffee in Body Weight of
Hypercholesterolemia Male Albino Rats
To determine the effect of Orlistat drug and Green
coffee in the body weight and lipid profiles in
hypercholesterolemia rats.

70. Material and Methods
70
40 male Albino rats (190-210g)
 Control - normal diet
 Control rats fed with high fat diet
 Rats fed with high fat diet - 4 mg/kg bw/day Orlistat
 Rats fed with high fat diet - 2.5 g/kg bw/day Green Coffee (powder)
Blood was collected from all groups at zero time
and after 4 weeks
After 4 weeks.
n=10
Plasma glucose and lipid profile levels and Body weight was measured

71. 71
Table 1: Initial and final body weight in study groups
Study groups Body weight (kg) Percentage
At zero time After 4 weeks
Control rats (Normal diet) 172 225 24%
Control rats (HFD) 193 320 40%
Green coffee (HFD) 184 233 22%
Orlistat (HFD) 190 213 11%

72. 72
Table 2: Plasma glucose and lipid profile levels of different high fat
diet groups
Parameters
Control rats
(Normal diet)
At zero time
Orlistat
after 4
weeks
Percentage
Green coffee
after 4
weeks
Percentage
Cholesterol
(mg/dl)
183 133 28% 148 20%
Triglyceride
(mg/dl)
196 155 21% 139 30%
LDL
(mg/dl)
64 46 29% 53 18%
HDL
(mg/dl)
26 39 34% 41 37%
Glucose
(mg/dl)
316 285 10% 263 17%

73.  Both the Green Coffee and Orlistat drug reduced the body
weight and lipid profile in Hypercholesterolemic rats.
 Ingestion of GCBE significantly reduced the HDL content
due to the presence of polyphenolic substance called CGA
than in Orlistat drug.
73
Conclusion

74. Summary
 Obesity has been emerged as a most epidemic health problem, which causes other
health complexes such as Diabetes, Cardiovascular diseases, Hypertension and
Cancer etc.
 In this context a natural phytochemical present highly in Green coffee called
Chlorogenic acid (CGA), belongs to the family Caffeoylic Acid has got considerable
media attention as an effective antiobesity agent.
 The different scientific evidences on CGA proves its anti-inflammation, antioxidant,
anti hypertensive, anti diabetic and antimicrobial properties.
 Administration of CGA inhibited hepatic G6Pase expression and activity, reduces
hepatic steatosis, improved lipid profiles and skeletal muscle glucose uptake.
 CGA up regulates AMPK (Adenosine Monophosphate Protein Kinase) pathway and
suppress the hepatic glucose production and fatty acid synthesis, thereby reduces
body weight.
74

75. Cont ….
 Hypocholesterolemic effect of CGA leads to Atheroscleroprotective,
Cardioprotective and Hepatoprotective acticity by increasing the Adiponectin
and Fat oxidation.
 The Hypocholesterolemic effect of CGA are probably due to the increase in fatty
acids unitization in liver through the up regulation of PPAR (Peroxisome
proliferation Activator Receptor) gene expression.
 CGA oxidizes more fat by supressing SREBP (Sterol Regulatory Element
Binding Protein) gene, which regulates the Cholesterol synthesis in the liver.
 Ingestion of CGA stimulated fat oxidation without an adverse effect on sleep
quality; rather, it shortened sleep latency.
 Both the Green Coffee and Orlistat drug reduced the body weight and lipid
profile in Hypercholesterolemic rats.
 The presence of Chlorogenic acid in green coffee bean extract reduced the weight
effectively in obese people.
75

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lowering and fatty liver attenuating properties in Hypercholesterolemic rats induced with a high-
cholesterol diet. Phytotherapy Research. 3(3): 1-7.
ERNEST, S., 2013, Distribution of Chlorogenic Acid in Plants. Archives of Biochemistry and
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body composition in obese women. Asia. Pac. J. Clin. Nutr. 26(6):1048-1054.
INSUNG, P., RYUJI, O., HITOMI, O., MOMOKO, K., SAYAKA, H. AND KUMPEI, T., 2017, Effects
of sub acute ingestion of chlorogenic acids on sleep architecture and energy metabolism through
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78
Cont ….

79. 79
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