Upload
dinhlien
View
215
Download
1
Embed Size (px)
Citation preview
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
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