The Role of LCPUFA in Obesity - Sickkids · The Role of LCPUFA in Obesity. ... Edmonton, Alberta, Canada . ... Data from NHANES 1999-2000 for U.S. population based on 24h recall and

by

M.Tom Clandinin

The Role of LCPUFA in Obesity

The Alberta Institute for Human NutritionThe University of AlbertaEdmonton, Alberta, Canada

How big is the Conceptual Problem?

•

Some assumptions:–

150lb teenager–

Gain is 10 lbs of body fat each decade

↓

190-200 lbs by age 60

–

~1 lb per year (adipose)

↓

400 grams of triglyceride/year

(~380 grams of fatty acid/year)

–

~1 gram of fatty acid/day

•

Approximately–

9 cal/day in excess → 1 lb/year–

18 cal/day in excess → 2 lbs/year<0.5% of energy intake

What’s the Concept to be Understood?

•

Very small imbalance in intake versus expenditure results in fat accumulation

•

“Small”

metabolic efficiencies matter to the whole body composition

•

What are some of these “small”

expenditures or efficiencies??

Has advice to increase PUFA intake contributed to obesity?

•

Notion that PUFA healthy Saturates not healthy

•

Affects food selection and fat sources

•

What is the PUFA intake of children?

Fat Intakes of Children in Regions of Canada

(% Energy Intake)AGE Fat PUFA P/S n-3

1.5-5 years (FFQ)

Vancouver Area

Innis et al (2004)

32.7 3.6 0.3 0.7 18:3

Grade School Students (FFQ)

Nova Scotia Veugelers et al (2005)

30.3 (26% Prevalence of inadequacy)

Grade 6-8 Students (24 hr)

Ontario

Hanning et al (2007)

29 3 0.3

Guelph (3 day weighted)

Holub (2008, in press)

Average Daily Nutrient Intake1

for

Children (n=78)

Aged 4-7

Nutrients per Day X ± SD RangeCalories (kcal) 1760 ± 440 1060 –

3370Protein (% of total calories) 14 ± 2.4 7.0 -

20.0Carbohydrate (% of total kcal) 56 ± 6.0 42 –

70Fat (% of total kcal) 33 ± 4.5 22 –

43Saturated Fat 12 ± 2.4 5.6 –

17Monounsaturated Fat 12 ± 2.3 6.1 –

17Polyunsaturated Fat

1 As assessed by 3 day food records

5.1 ± 1.6 2 –

10

Average Daily PUFA Intake for Children (n=78)

Aged 4-7

Assessed by 3 day Food Records

Fatty Acids X ± SD RangeLinoleic acid 18:2 (% of total kcal) 3.9 ± 1.6 1.0 –

8.2Linoleic Acid 18:3 (% of total kcal) 0.36

± 0.2 0.067 –

1.32Arachadonic acid 20:4 (mg) 57

± 35 1.2 –

180Eicosapentaenoic acid 20:5 (mg) 17 ± 36 0.0 –

200Docosahexaenoic acid 22:6 (mg)1 37

± 63 0.0 –

350N-3 (g) 0.75 ± 0.5 0.18 –

3.1N–6 (g)

1 Median = 16.5

7.4 ± 3.3 2.6 -

19

Average Daily DHA Intake for Children (n=78) Aged 4-7

DHA intake (mg/day) was expressed in 10mg/day increments and the

number of children in each 10mg/day increment displayed. Approximately 35% had intakes of <10mg/day.

Estimated Fatty Acid Intake of Americans (1999-2000)

16:016:0 18:018:0 18:218:2

6.26.2 2.82.8 6.06.0

MenMen 2020--39y39y 6.26.2 2.82.8 5.85.8

4040--59y59y 6.06.0 2.82.8 5.95.9

60+y60+y 6.06.0 2.82.8 6.16.1

WomenWomen 2020--39y39y 6.16.1 2.82.8 6.26.2

4040--59y59y 6.06.0 2.82.8 6.36.3

60+y60+y 6.06.0 2.72.7 6.56.5

Both sexes/All agesBoth sexes/All ages11

Values represent means as % of energy, assuming fat intake at 33Values represent means as % of energy, assuming fat intake at 33% of energy.% of energy.11Excludes nursing infants and children.Excludes nursing infants and children.

Data from NHANES 1999Data from NHANES 1999--2000 for U.S. population based on 24h recall and coded to 2000 for U.S. population based on 24h recall and coded to USDAUSDA’’s Survey Nutrient Database (versions 1994s Survey Nutrient Database (versions 1994--96 and 1998).96 and 1998).

(Ervin et al., (Ervin et al., Advance data,Advance data, 2004)2004)

What are the ‘efficiencies’

contributed by dietary PUFA?

•

Absorption (infant / adult) •

Mitochondrial ATP (rat / chick)

•

Insulin Action (rat) •

Selective Oxidation (young adults)

•

Lipogenesis (adult) •

Synthesis of individual fatty acids (adult)

Coefficients of Absorption for Individual Fatty Acids

60

65

70

75

80

85

90

95

100

C16:0 C18:0 C18:1 C18:2

Coe

ffici

ents

of A

bsor

ptio

n (%

, mea

n ±

SD)

Chappell et al., J of Pediatrics, 1986

_________________________________Dietary Fatty Acid

X + SD% absorbed / ingested

Stearic Acid 91.87 + 5.5

Oleic Acid 97.42 +

2.7 *

Linoleic Acid

TOTAL FAT

99.43 +

0.2 *

97.00 +

2.0

* Significantly different from stearic acid (p < 0.01)

Absorption of fatty acid by young adults

Jones et. al., AJCN, 1985

Effect of dietary fatty acids on mitochondrial structure and function

Diet Fat ADP/O

Rat Chick

Low 18:2High 18:1

High 18:2Low 18:1

Clandinin, J Nutr, 1978

1.61 +

0.23a 1.93 +

0.09a

2.01 +

0.05b 2.53 +

0.09b

Energy, consumption and energy utilization of chicks pair-fed experimental diets for 23 days

DietEnergy

Consumption1

(kcal)

Fat Gain (g) Protein Gain (g)

Kcal gain / Kcal consumed2

3,360 +

42a

3,285 + 39a

78.0 +4.0a

82.5 +

2.7b

123.2 + 3.2a

125.8 +

2.4a

0.426 +

0.012a

0.454 +

0.007b

1 Calculated using determined metabolizable energy values for the diets. 2 Kilocalories of energy gained per kilocalorie of metabolizable energy consumed.

Clandinin et al.,

J. Nutr, 1979

Low 18:2High 18:1

High 18:2Low 18:1

Relationship between the dietary P/S and insulin binding to rat adipocytes

Regression lines were constructed for the dietary P/S ratio vs the mean amount of insulin bound at the five insulin concentrations measured.

Field et. al. J. Nutr 1989

(----) Saturated fatty acid and content of PE;

( ) monounsaturated fatty acid

content of PE; ( ) polyunsaturated fatty acid content of PE

Field et. al. J. Nutr 1989

Relationship between dietary P/S ratio, fatty acid composition of phospholipids and insulin binding

Relationship between insulin bound and glucose transported by rat at adipocyte

Clandinin et. al. Biomembranes et Nutrition, 1989

Values illustrated are group means for control animals fed the high P/S diet ; control animals fed the low P/S diet ; diabetic animals fed the high P/S diet ; diabetic animals fed the low P/S diet

Percent of absorbed 13C excreted in breath CO2 after oral feeding of [1-13C] stearic, [1-13C] oleic and

[1-13C] linoleic acids by young adults

•Oleate and linoleate preferred substrates for oxidation

Jones et. al. AJCN 1985

Cumulative percent absorbed 13C excreted in breath CO2

after feeding of [1-13C] stearic, [1-13C] oleic and [1-13C] linoleic acids

•Oleate and linoleate preferred substrates for oxidation

Jones et. al. AJCN 1985

Fasting total fatty acid synthesis in VLDL- triglyceride

Net de novo fatty acids was measured in control and diabetes subjects following 3 days of lower (LF) and higher (HF) fat intake.

Fasting VLDL-triglyceride fatty acid synthesis

Net synthesis of individual fatty acids in VLDL-TG of control and diabetes subjects following lower or higher fat intake for 3 days.

Individual variation in net de novo fatty acids in VLDL-TG for control subjects following 3 days of lower fat (left bar) and higher fat (right bar) diets at

12h fasting

Increased fractional synthesis rate was associated with BMI

Can we quantitate

the ‘efficiencies’

to account for 10 kcal/day?

Impact of Fatty Acid Absorption

Current Fat Intake (g) Diet Change

Saturated 22 11

PUFA 7 7

Monene 20 31

Estimated net fat absorption = (19.8 + 7 + 19.6) (9.9 + 7 + 30.4)

46.4 47.3

Net difference of conservatively 0.9g of fat / day

Impact of PUFA intake on ATP synthesisRatIncreasing 18:2

vs monoene:

20% ↑

in ATP produced per O2

vs saturate: 12% ↑

in ATPase activity (P/S of 1.0 vs 0.4)

low vs high fat:

>50% ↑

in ATPase activity

Growing ChickIncreasing 18:2

vs monoene:

25% ↑

in ATP produced per O2

energetic Efficiency: ↑

by ~ 6%(Kcal gain / Kcal consumed)

fat gain:

↑

by ~ 5%, 4.5g fat over 3 weeks

Impact of PUFA intake on insulin action

Rat Adipocytes

Increase in PUFA to saturates (0.2 to 1.0)

•

↑

insulin binding up to 3 fold at low insulin concentrations

•

Continue to transport glucose as more insulin is bound

•

Favors more lipogenesis from glucose

Preferential oxidation of individual fatty acids

•

Switching from saturated to polyunsaturated fat intake favors oxidation of unsaturated fatty acid intake

•

This may be most energetically efficient

•

Dietary fatty acid composition modulates the proportion of carbohydrate and fat oxidized

Impact of fat level on lipogenesis and synthesis of individual fatty acids

•

High fat intake downregulates synthesis of 16:0

•

Downregulation is likely fast, perhaps meal to meal

•

In Type 2 diabetes the low fat upregulation does not work the same

•

Very large subject to subject variation in responsiveness

•

If we are encouraging children to eat more PUFA then we best empower them to run it off playing outside!

•

Can we expect to resolve this overall imbalance in intake vs expenditure with a background of other nutrient inadequacies (ex. N-3 fatty acids)?