Effect of fructose overfeeding. hepatic de novo lipogenesis and insulin sensitivity in healthy males

Transcription

1 Effect of fructose overfeeding and fish oil administration on hepatic de novo lipogenesis and insulin sensitivity in healthy males David Faeh 1,2, Kaori Minehira 1, Jean-Marc Schwarz 3,4, Raj Periasami 4, Park Seongsu 3, Luc Tappy 1 1 Department of Physiology, University of Lausanne, 1005 Lausanne, Switzerland 2 University Institute of Social and Preventive Medicine, 1005 Lausanne, Switzerland 3 Department t of Medicine, i University it of California i at San Francisco, San Francisco, USA 4 Basic Science, Touro University, Mare lland, CA, USA

2 Introduction Estimated intakes of Bray et al, 2004 total fructose ( ), high-fructose corn syrup (HFCS, ) and free fructose ( ).

3 Introduction S u g a r c o n s u m p t i o n i n S w i t z e r l a n d person per year kilo / Time period (year) Sources: : 2., 3. & 4. CH Ernährungsbericht, : Schweizerischer Bauernverband

4 Introduction Annual per capita consumption of sugar sweetened drinks in Switzerland: 89.3 kilo* *Source: Schweizerischer Bauernverband ( )

5 Background Metabolic consequences of ffructose overfeeding 1. Hypertriglyceridemia (rodents & humans) 2. Increased hepatic de novo lipogenesis (DNL) (rodents & humans) 3. Hepatic, adipose tissue and whole body insulin resistance (rodents) Huang, et al., 1997; Bantle et al., 2000; Parks et al., 2000; Pagliassotti et al., 2004

6 Action of insulin David FAEH

7 Insulin resistance David FAEH

8 Insulin resistance David FAEH

9 Background Metabolic impact of fish oil supplementation. Fish oil 1. decreases triglycerides gy (rodents & humans) 2. may suppress hepatic lipogenic enzymes (FAS, ACC, SREBP-1, etc.) (in vitro and rodents) 3. may prevent development of insulin resistance (rodents) Podolin et al., 1998; Xu et al., 1999

10 Aims David FAEH To test the effect of fructose and fish oil on blood triglycerides, glucose, lactate hepatic DNL insulin resistance (hepatic, adipose tissue and whole body)

11 Subjects Seven healthy men Mean age: 24.7 ± years Mean BMI: 22.0 ± 075kg/m Mean body fat: 16.5 ± 07% 0.7 % Mean waist circ.: 80 ± 29cm 2.9

12 Study design Each subject was examined after every of the four conditions (randomized): Fish oil (7.2 g per day for 4 weeks) Fructose (3 g per kilo BW per day for 6 days = plus 30% of energy intake) Fish oil and Fructose Control

13 Study design Isocaloric diet for 6 days DIETARY INTERVENTION METABOLIC INVESTIGATION

14 Study design Isocaloric diet for 6 days ± Fish oil 2200 Day 0 Day 28 DIETARY INTERVENTION METABOLIC INVESTIGATION

15 Study design Isocaloric diet for 6 days ± Fish oil ± Fructose 2200 Day 0 Day 22 Day 28 DIETARY INTERVENTION METABOLIC INVESTIGATION

16 Study design Isocaloric diet for 6 days ±Fish oil ± Fructose [1-13 C] acetate Day 0 Day 22 Day 28 t= Day 29 DIETARY INTERVENTION METABOLIC INVESTIGATION

17 Study design Isocaloric diet for 6 days 6,6-2 H 2 glucose ±Fish oil ± Fructose 0500 [1-13 C] acetate Day 0 Day 22 Day 28 t= Day 29 DIETARY INTERVENTION METABOLIC INVESTIGATION

18 Study design Isocaloric diet for 6 days 6,6-2 H 2 glucose 0500 ±Fish oil ± Fructose [1-13 C] acetate Insulin (2 steps) Day 0 Day 22 Day 28 t=0 t=90 t= Day 29 DIETARY INTERVENTION METABOLIC INVESTIGATION

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23 Results (fasting) Control n-3 fish fatty oil acids Triglyce erides (m mmol/l) high-fructose diet n-3 fish fatty oil acids & high-fructose diet 0.2 0

24 Frac ctional DNL (%) Hepa atic 14% 12% 10% 8% 6% 4% 2% Results (fasting) Control n-3 fish fatty oil acids high-fructose diet n-3 fish fatty oil acids & highfructose diet 0%

25 Results (fasting) 5.2 Control 5.1 Fish oil administration Glucos se (mmo ol/l) High-fructose diet Fish oil administraton & high-fructose diet

26 Results (fasting) 75 Control Insu ulin (pmo ol/l) Fish oil administration High-fructose diet Fish oil administraton & high-fructose diet 45 40

27 Results (clamp) A * NE EFA (μmol/l) * * 0 B 100 initial value) NEFA (% of i * Time (min) * control n-3 fish fatty oil acids high-fructose diet n-3 fish fatty oil acids & high-fructose diet

28 Results (clamp) per min) Control n-3 fish fatty oil acids high-fructose diet n-3 fish fatty oil acids & high-fructose diet EGP (μmol/kg 6 * * * * 2 fasting basal Time (min)

29 Results (clamp) A 10 Glucose (mm mol/l) B 400 Insulin (pm mol/l) C GIR (mmol/kg p er min) Time (min) control n-3 fish fatty oil acids high-fructose diet n-3 fish fatty oil acids & high-fructose diet

30 Conclusion After 6 days of fructose overfeeding, mean fasting TG increased significantly by 79% mean DNL increased significantly 6-fold hepatic and adipose tissue insulin sensitivity decreased significantly whole body insulin sensitivity was not affected

31 Conclusion Fish oil supplementation significantly attenuated fructose induced increase of blood TG and tended to reduce fructose induced DNL (ns) did not affect impaired insulin sensitivity associated to fructose overfeeding

32 Perspectives Long term (weeks) Fructose supplementation might increase Intra Myocellular (IMCL) and Intra Hepatocellular Lipids (IHCL) impair i muscle insulin sensitivity and cause hyperinsulinemia (as in rodents: Podolin et al., 1998)

33 Further aspects of fructose Fructose can lead to increased food intake because unlike glucose, it 1. does not cross the blood-brain b barrier 2. does not increase insulin and leptin concentrations and decreases ghrelin Havel, 2001; Teff, et al., 2004

34 Further aspects of fructose Subjects consuming fructose or sucrosesweetened beverages did not compensate additional energy intake by those drinks by reducing their energy intake from other sources Tordoff, et al., 1990; Anderson et al., 1989; Raben et al., 2002

35 Further aspects of fructose Prolonged ad libitum consumption of fructose can increase body weight Nurses Health Study: consumption of larger amounts of soft drinks was associated with greater weight gain and increased risk for diabetes Tordoff, et al., 1990; Anderson et al., 1989; Schulze et al., 2004

36 Further aspects of fructose Children, who consume more than 265ml of soda /day had a 15% higher energy intake than those who did not consume soft drinks For each soda beverage BMI and frequency of Obesity increased in children Harnack, et al., 1999; Ludwig, et al. 2001

37 Further aspects of fructose Education program aimed to reduce soda intake prevented further weight gain in school children A 3-year intervention aimed at reducing soft drink intake lowered fasting insulin levels in students James, et al., 2004; Ritenbaugh et al., 2003

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39 Thanks to Christine Cayeux Françoise Secrétan Rodrigue Stettler Eunika Rossi Nathalie Stefanoni Valentine Rey Philippe Schneiter

40 David FAEH