Dr Obeid Phosphorus Qatar (1) .pdf

The role of phosphorus in the
regulation of food intake.

Omar Obeid, PhD
Department of Nutrition & Food Science
American University of Beirut
Lebanon

Energy Balance Equation

Intake

Hunger
Satiety
Nutrient Absorption

Expenditure

Metabolic Rate
Physical Activity
Thermogenesis

Energy Balance
EI - EE = 100 kcal/day
40kg

12kg
8kg
4kg

Year 1

Year 2

Time

Year 3

Year 10

Daily Energy Intake

Inter-meal Interval

Meal Size

Meal Number

Satiety

Satiation

Factors affecting food intake

CNS
Factors
Circulating
Factors

Sensory
Stimulation

Digestive Factors
(GI Factors)
Hepatic
Factors

Food
Intake

Neurological
Factors

Eating
Environment
Hormonal
Factors

Metabolic
factors

Habits
Beliefs

Metabolism and Eating
A study involving long-term iv
alimentation
29 healthy patients over 8 months:
Stable body weight.
No or little hunger
(McCutcheon & Tennissen, 1989)

Rats: TPN
Food intake: 70-90% lower
(Walls et al, 1991, Beverly et al 1994)

Metabolism and Eating

Hunger
No change in
body weight

TPN
IV
Blood

Significance of metabolic factors in the control of
eating behavior
McCutcheon & Tennissen ( 1989), Walls et al (1991), Beverly et al (1994)

Metabolism and Food Intake
Human, Monkeys, Rat, Rabbits, Pigs

Food
FoodIntake
Intake


Not a direct
action !!
2 – DG (IV)
5 – TG (IV)
2,5 – AM

Glucose Oxidation

2-deoxyglucose
5-thioglucose
2,5-anhydro-mannitol

Hepatic Metabolic Sensors

Food Intake 


Glucose
Fructose
Glycerol
Pyruvate
Amino acid
DHB

Metabolism and Food Intake
Glucose (iv) or glucose plus amino acids in
rats Only during the feeding period Reduced
food intake by 70% of infused kcals
(Walls & Koopmans, 1989)

Intra-meal hepatic-portal infusion of
glucose reduces spontaneous meal size
in rats
(Langhans et al, 2001)

Metabolism and Food intake

Some general measure of energy
flow in metabolism, rather than Δ
in the utilization of a particular
fuel controls eating.
Hepatic Metabolic sensors

Nature of Hepatic Metabolic Sensors
2,5-anhydro-mannitol (2,5-AM), Fructose analogue
 Hyperphagic effect
Hepatic branch vagotomy blocked eating
response
Radioactive 2,5-AM: liver but not brain
Rapidly P-tion, trapping hepatic P and  ATP
Addition of P: attenuate action

Administration of L-ethionine
Bind adenine  low ATP
Stimulate feeding

Nature of Hepatic Metabolic Sensors
Food Intake
Intake


Pi
L-ethionine
2,5 - AM

L-ethionine + Adenine  No ATP

2,5-AMP  No ATP

Friedman 1999 (Rats)
(Methyl Palmoxirate)

a
a,b

4

a

b

2

b
a

1

4
a
a

3
b
2

a
b

c

0

1
0

Liver glycogen (%wet wt)

Phosphorylation potential

5

0

3

1

2
1

0

2

3

ATP/ADP

ATP (mmol/g)

3

5

a

c

4
Food intake (g/3h)

4

b

3
2

a

a

1
0

V
1
5
10
Methyl palmoxirate (mg/kg)

V
1
10
V
1
10
Methyl palmoxirate (mg/kg)
Friedman et al. 1999 Am. J. Physiol. 276, 45: R1046–R1053, 1999

Liver ATP of obese Zucker Rats
SerKova et al (2006) Journal of Hepatology 44: 956-962

3

Hepatic ATP stores in Lean and ob/ob mice
Chavin et al (1999) Journal of Biological Chemistry, 274 (9): 5692-5700

2.5
1.2

ATP/ADP

2

1.0

ATP/Std

1.5
1

0.5

0.8

0.6
0.4
0.2

0

0
Lean

Obese

Lean

Obese

Basal ATP spectra in each BMI group
Nair et al. The American Journal of Gastroenterology 2003; 98(2): 466-470

Amplitude of basal  ATP spectra

Correlation between BMI and fractional ATP recovery.
Cortez-Pinto et al. JAMA (1999) 282(17): 1659-1664.
36
33
30

r= 0.63, p= 0.02

27

24
21
18
15
12
9
6
15

17 19

21 23

25

27

29

31

BMI (kg/m2)

33

35

37

39

41

Phosphorus
Constant fractional absorption
Low cellular storage (liver)
Low ECF Pi
 cellular dysfunction

The Effect of glucose ingestion (OGTT) on
Phosphorous status.
4.5

5.5

GP

G

G

P

4

Inorganic Phosphate (mg/dl)

5

Total phosphate (mg/dl)

GP

P

4.5

4

3.5

3

3.5

3

2.5

2

2.5

1.5
0

30

60

90

120

150

Time (min)

180

210

240

0

30

60

90

120

150

Time (min)

180

210

240

Relationship between the concentrations of Pi &
ATP of the intact rat
Direct & significant relationship between Pi and ATP (P <0.001)

 Liver .  Renal cortex .  Fructose loading alone at 20µmol/g.
 Fructose loading alone at 40µmol/g. a Higher dose of fructose combined with 2
µmol/g adenosine
Morris RC et al. 1978The Journal of Clinical Investigation, 61: 209 -220

Phosphorous: Preload

-P

+P

Preload

80 minutes

Increased Phosphorus content of preload suppresses
Ad libitum energy intake at subsequent meal

Preload

Gender (n)

Age (years)

BMI (kg/m2)

Water

M (12)

23.8±4.4

23.4±3.0

Sucrose

M (5), F (5)

21.7±4.0

22.2±1.3

Fructose

M (10), F (10)

26.6±5.5

27.2±1.4

Glucose

M (11)

20.7±1.4

24.7±1.2

Obeid et al. International Journal of Obesity. 2010; 1-3

Increased Phosphorus content of preload suppresses
Ad libitum energy intake at subsequent meal
Fructose

Sucrose

1000

750

31%

500

250

Energy Intake (Kcal)

Energy Intake (Kcal)

1250
1000

33%

750
500
250

0

0

-P

+P

-P: No added Phosphorus to preload
+P: with 500mg of added Phosphorus to preload

-P

+P

Increased Phosphorus content of preload suppresses
Ad libitum energy intake at subsequent meal
Water

Glucose

1000

1750

27%

27%

750

Energy Intake (Kcal)

Energy Intake (Kcal)

1500
1250
1000
750

500

250

500
250

0

0

-P

-P

+P

-P: No added Phosphorus to preload
+P: with 500mg of added Phosphorus to preload

+P

Increased Phosphorus content of preload suppresses
Ad libitum energy intake at subsequent meal

Energy Intake (Kcal)

2000

Water

Sucrose

Fructose

Glucose

1500
*
1000
*

*

500
0
-P

+P

-P: No added Phosphorus to preload
+P: with 500mg of added Phosphorus to preload
Obeid et al. International Journal of Obesity. 2010; 33, 1446-8

**

Increased Phosphorus content of preload suppresses
Ad libitum energy intake at subsequent meal

Addition of Phosphorus to the different
preloads was associated with a
decrease in subsequent energy
intake (~30%)

Phosphorus and body weight
Serum phosphate was reported to be
inversely related to body weight
Lindgärde et al. Acta Medica Scandinavic 1977a; 202(1-6): 307 – 311.
Lind et al Eur J Clin Invest. 1993; 23(5):307-10.
Haglin et al. European Journal of Clinical Nutrition 2001; 55: 493-498.
Kalaitzidis et al Am J Kidney Dis 2005; 45:851-858.
Haap et al. European Journal of Clinical Nutrition (2006) 60, 734–739.
Park et al. Diabetes Research and Clinical Practice 2009; 83: 119– 125.
Lippi et al Diabetes Research and Clinical Practice 2009; 84: e3-e5.

Energy (%) from low phosphorus containing foods
Food Balance Sheet (FAO)

Low phosphorous containing foods
100

Lebanon
Saudi Arabia

Percentage of energy (%)

90

Egypt

80

70

60

50

40
1961

1966

1971

1976

1981

1986

Year

1991

1996

2001

2006

Conclusion
Food intake
Mainly controlled by signals from the liver
Signals are mainly derived from
substrates oxidation or ATP production

The Effect of Phosphorous ingestion on OGTT
200

200

G
G

150

Glucose (mg/dl)

GP

P

P

Insulin (µIU/ml)

GP

100

150

100

50

50

0

0
0

30

60

90

120
Time (min)

150

180

210

240

0

30

60

90

120
Time (min)

150

180

210

240

The Effect of Phosphorous ingestion on OGTT

40
G

GP

P

35
30

HOMA

25
20
15
10
5
0
0

30

60

90

120
Time (min)

150

180

210

240

The Effect of Phosphorous ingestion on OGTT
4.5

5.5

GP

G

G

P

4

Inorganic Phosphate (mg/dl)

5

Total phosphate (mg/dl)

GP

P

4.5

4

3.5

3

3.5

3

2.5

2

2.5

1.5
0

30

60

90

120

150

Time (min)

180

210

240

0

30

60

90

120

150

Time (min)

180

210

240