The Role of LCPUFA in Obesity. M.Tom Clandinin. The Alberta Institute for Human Nutrition The University of Alberta Edmonton, Alberta, Canada

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1 The Role of LCPUFA in Obesity by M.Tom Clandinin The Alberta Institute for Human Nutrition The University of Alberta Edmonton, Alberta, Canada

2 How big is the Conceptual Problem? Some assumptions: 150lb teenager Gain is 10 lbs of body fat each decade 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

3 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??

4 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?

5 Fat Intakes of Children in Regions of Canada years (FFQ) Vancouver Area Innis et al (2004) (% Energy Intake) AGE Fat PUFA P/S n :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) Guelph (3 day weighted) Holub (2008, in press)

6 Average Daily Nutrient Intake 1 for Children (n=78) Aged 4-7 Nutrients per Day X ± SD Range Calories (kcal) 1760 ± Protein (% of total calories) 14 ± Carbohydrate (% of total kcal) 56 ± Fat (% of total kcal) 33 ± Saturated Fat 12 ± Monounsaturated Fat 12 ± Polyunsaturated Fat 5.1 ± As assessed by 3 day food records

7 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 ± Linoleic Acid 18:3 (% of total kcal) 0.36 ± Arachadonic acid 20:4 (mg) 57 ± Eicosapentaenoic acid 20:5 (mg) 17 ± Docosahexaenoic acid 22:6 (mg) 1 37 ± N-3 (g) 0.75 ± N 6 (g) 7.4 ± Median = 16.5

8 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.

9 Estimated Fatty Acid Intake of Americans ( ) Both sexes/all ages 1 16:0 18:0 18: Men 20-39y y y Women 20-39y y y Values represent means as % of energy, assuming fat intake at 33% % of energy. 1 Excludes nursing infants and children. Data from NHANES for U.S. population based on 24h recall and coded to USDA s s Survey Nutrient Database (versions and 1998). (Ervin et al., Advance data, 2004)

10 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)

11 Coefficients of Absorption for Individual Fatty Acids Coefficients of Absorption (%, mean ± SD) C16:0 C18:0 C18:1 C18:2 Chappell et al., J of Pediatrics, 1986

12 Absorption of fatty acid by young adults Dietary Fatty Acid X + SD % absorbed / ingested Stearic Acid Oleic Acid * Linoleic Acid * TOTAL FAT * Significantly different from stearic acid (p < 0.01) Jones et. al., AJCN, 1985

13 Effect of dietary fatty acids on mitochondrial structure and function Diet Fat ADP/O Rat Chick Low 18:2 High 18: a a High 18:2 Low 18: b b Clandinin, J Nutr, 1978

14 Energy, consumption and energy utilization of chicks pair-fed experimental diets for 23 days Diet Energy Consumption 1 (kcal) Fat Gain (g) Protein Gain (g) Kcal gain / Kcal consumed 2 Low 18:2 High 18:1 3, a a a a High 18:2 Low 18:1 3, a b a b 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

15 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

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

17 Relationship between insulin bound and glucose transported by rat at adipocyte 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 Clandinin et. al. Biomembranes et Nutrition, 1989

18 Percent of absorbed 13 C excreted in breath CO 2 after oral feeding of [1-13 C] stearic, [1-13 C] oleic and [1-13 C] linoleic acids by young adults Oleate and linoleate preferred substrates for oxidation Jones et. al. AJCN 1985

19 Cumulative percent absorbed 13 C excreted in breath CO 2 after feeding of [1-13 C] stearic, [1-13 C] oleic and [1-13 C] linoleic acids Oleate and linoleate preferred substrates for oxidation Jones et. al. AJCN 1985

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

21 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.

22 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

23 Can we quantitate the efficiencies to account for 10 kcal/day?

24 Impact of Fatty Acid Absorption Current Fat Intake (g) Diet Change Saturated PUFA 7 7 Monene Estimated net fat absorption = ( ) ( ) Net difference of conservatively 0.9g of fat / day

25 Impact of PUFA intake on ATP synthesis Rat Increasing 18:2 vs monoene: 20% in ATP produced per O 2 vs saturate: (P/S of 1.0 vs 0.4) 12% in ATPase activity low vs high fat: >50% in ATPase activity Growing Chick Increasing 18:2 vs monoene: 25% in ATP produced per O 2 energetic Efficiency: by ~ 6% (Kcal gain / Kcal consumed) fat gain: by ~ 5%, 4.5g fat over 3 weeks

26 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

27 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

28 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

29 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)?

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