The Role of LCPUFA in Obesity by M.Tom Clandinin The Alberta - - PowerPoint PPT Presentation

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M.Tom Clandinin The Role of LCPUFA in Obesity

The Alberta Institute for Human Nutrition The University of Alberta Edmonton, 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

• besity?
• 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 Range Calories (kcal) 1760 ± 440 1060 – 3370 Protein (% of total calories) 14 ± 2.4 7.0 - 20.0 Carbohydrate (% of total kcal) 56 ± 6.0 42 – 70 Fat (% of total kcal) 33 ± 4.5 22 – 43 Saturated Fat 12 ± 2.4 5.6 – 17 Monounsaturated Fat 12 ± 2.3 6.1 – 17 Polyunsaturated 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 Range Linoleic acid 18:2 (% of total kcal) 3.9 ± 1.6 1.0 – 8.2 Linoleic Acid 18:3 (% of total kcal) 0.36 ± 0.2 0.067 – 1.32 Arachadonic acid 20:4 (mg) 57 ± 35 1.2 – 180 Eicosapentaenoic acid 20:5 (mg) 17 ± 36 0.0 – 200 Docosahexaenoic acid 22:6 (mg)1 37 ± 63 0.0 – 350 N-3 (g) 0.75 ± 0.5 0.18 – 3.1 N–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)

16:0 16:0 18:0 18:0 18:2 18:2 6.2 6.2 2.8 2.8 6.0 6.0 Men Men 20 20-

• 39y

39y 6.2 6.2 2.8 2.8 5.8 5.8 40 40-

• 59y

59y 6.0 6.0 2.8 2.8 5.9 5.9 60+y 60+y 6.0 6.0 2.8 2.8 6.1 6.1 Women Women 20 20-

• 39y

39y 6.1 6.1 2.8 2.8 6.2 6.2 40 40-

• 59y

59y 6.0 6.0 2.8 2.8 6.3 6.3 60+y 60+y 6.0 6.0 2.7 2.7 6.5 6.5 Both sexes/All ages Both sexes/All ages1

1

Values represent means as % of energy, assuming fat intake at 33 Values represent means as % of energy, assuming fat intake at 33% of energy. % of energy.

1 1Excludes nursing infants and children.

Excludes nursing infants and children. Data from NHANES 1999 Data 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 USDA USDA’ ’s Survey Nutrient Database (versions 1994 s 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

Coefficients of Absorption (%, mean ± 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 18:2 High 18:1 High 18:2 Low 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

Diet Energy 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 18:2 High 18:1 High 18:2 Low 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

• ral 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 synthesis

Rat Increasing 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 Chick Increasing 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)?