1. Conjugated linoleic acid (CLA): A good fat? Yeonhwa Park Department of Food Science University of Massachusetts, Amherst

2. Yeonhwa Park Dept. Food Science University of Massachusetts Discovery of CLA

3. Yeonhwa Park Dept. Food Science University of Massachusetts c9, t11 CLA t10, c12 CLA Linoleic Acid (c9,c12) Reprinted with permission from the Journal of Chemical Education 73(12):A302–A303 (1996). Copyright Division of Chemical Education, Inc. cis-9,cis-11 cis-9,trans-11 trans-9,cis-11 trans-9,trans-11 cis-10,cis-12 cis-10,trans-12 trans-10,cis-12 trans-10,trans-12

4. Yeonhwa Park Dept. Food Science University of Massachusetts CLA reduces cancer incidences reduces severity of atherosclerosis regulates signal transduction enhances immune function reduces asthma in animal models is a growth factor in rats reduces body fat while increases lean body mass

5. Yeonhwa Park Dept. Food Science University of Massachusetts Control CLA % Water 66.29 70.88* % Protein 17.76 18.58* % Fat 10.13 4.34* % Ash 3.08 3.24* ECW (g) 32.4 32.2 ControlCLA Body Composition

6. Yeonhwa Park Dept. Food Science University of Massachusetts Control CLA 3T3-L1 adipocytes

7. Yeonhwa Park Dept. Food Science University of Massachusetts Effects of c9,t11 and t10,c12 isomers on intracellular triacylglycerol 3T3-L1 Adipocytes 0 50 100 150 200 a Control b t-10,c -12 a t-9,t -11 b CLA-Mix a c-9,t -11 TG in cell (  g/mg protein)

8. Yeonhwa Park Dept. Food Science University of Massachusetts CLA reduces adipocyte cell size Xu et al. J. Nutr. (2003) 133: 663-667 Cells were prepared from parametrial adipose tissue of mice after 4 day feeding with either control or CLA supplemented diet.

9. Yeonhwa Park Dept. Food Science University of Massachusetts lipid filling lipolysis differentiation LPL SCD Lipogenesis Cell death apoptosis Adipocytes and Preadipocytes PreadipocyteAdipocyte Hormone Sensitive Lipase Increase in cell numberIncrease in cell size FAS aP2 PPAR 

10. Yeonhwa Park Dept. Food Science University of Massachusetts lipid filling lipolysis differentiation LPL SCD lipogenesis Cell death apoptosis CLA Effects Evidence Strong evidence Evidence ? A model for the effects of CLA on adipocytes and preadipocytes Preadipocyte Adipocyte Hormone Sensitive lipase FAS aP2 PPAR 

11. Yeonhwa Park Dept. Food Science University of Massachusetts CLA’s effects on lipid metabolism Liver Adipose tissue CLA increases fat use as an energy source and improves immune response resulting in less muscle wasting CLA decreases fat deposit, increases fat release, decreases preadipocyte differentiation, and increases apoptosis of preadipocytes and/or adipocytes CLA decreases ApoB secretion CLA increases energy expenditure

12. Yeonhwa Park Dept. Food Science University of Massachusetts Pathogen BRAIN Tumor necrosis factor-  Muscle wasting Lymphocyte proliferation Macrophage Gut Peptides GUT Cachexia CLA’s effects on immune function IL-1 AA ↑PGE 2 CLA reduces TNF-  secretion and its adverse effect

13. Yeonhwa Park Dept. Food Science University of Massachusetts Correlation between CLA and calcium on total ash 0.5% Calcium as CaHPO 4 0.5% Calcium as CaHPO 4 and 0.16% as CaCO 3

14. Yeonhwa Park Dept. Food Science University of Massachusetts CLA and calcium interaction n=9 Park Y, Park Y, Rhee S, Park GK (2006) FASEB J 20, A570. CaCO 3

15. Yeonhwa Park Dept. Food Science University of Massachusetts CLA’s effect on calcium deposition Mouse mesenchymal stem cell line, differentiated into osteoblasts 100  M CLA-mix and 50  M c9,t11 and t10,c12 CLA

16. Yeonhwa Park Dept. Food Science University of Massachusetts Molecular mechanism of CLA’s control on bone marrow adipogenesis and osteoblastogenesis

17. Yeonhwa Park Dept. Food Science University of Massachusetts Interaction of CLA isomers cis-9,trans-11 and trans-10,cis-12 isomers Synergistic or additive 1 –certain cancer model synergistic or additive Independent effects 2 –trans-10,cis-12 isomer: body fat reduction, inhibition of stearoyl-CoA desaturase, reduction of Hepatic ApoB secretion –cis-9,trans-11 isomer: improves growth performance Antagonistic effects 3 –trans-10,cis-12 isomer increases insulin resistance but cis-9,trans-11 isomer corrects this 1 Ip et al. (2002) Nutr. Cancer 43: 52-58/ Masso-Welch et al. (2004) J. Nutr. 134: 299-307 Masso-Welch et al. (2002) Cancer Res. 62: 4383-4389 2 Chin et al. (1994) J. Nutr. 124: 694-701/ Park et al. (1999) Lipids 34: 235-241 Storkson et al (2005) Nutr. Res. 25: 387-399/ Valeille et al. (2004) Br. J. Nutr. 91: 191-199 Cook et al. (1999) FASEB J. 13:A1023/ Park et al. (2000) BBA 1486: 285-292 3 Pariza et al. (2003) Adv. CLA Res Vol. 2, pp251-258

18. Yeonhwa Park Dept. Food Science University of Massachusetts Human studies >20 human trials 0.7g to 6.8g CLA /day 70-80% reported significant reduction of BF, BW, BMI, FM, or SAD, or enhancement of fat free mass 2 year trials without side effects (Gaullier et al. J. Nutr. 2005, 135: 778-784) Reported adverse effects –Metabolic syndrome: increased plasma glucose and insulin resistance –Correlated only with trans-10,cis-12 CLA isomer, not with CLA mixture

19. Yeonhwa Park Dept. Food Science University of Massachusetts Current/Possible Applications Dietary supplement –Reduces body fat –Improves immune responses –Cancer prevention Food fortification Animal Feed Overall saturation in fat increased because CLA increased saturated fatty acid, and reduced monounsaturated fatty acids. However, CLA also reduced severity of atherosclerosis. Courtesy of Dr. Mark Cook, University of Wisconsin-Madison

20. Yeonhwa Park Dept. Food Science University of Massachusetts Summary CLA reduces body fat by various mechanisms CLA improves immune response caused by immune stimulation CLA mixed isomer may be safe for human use

21. Yeonhwa Park Dept. Food Science University of Massachusetts Acknowledgements University of Massachusetts, Amherst Dr. Yooheon Park Dr. Kyuho Han Dr. Daehyun Noh Si-Yeon Rhee Faith Whitcomb Michael Terk