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European Journal of Nutrition

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01-10-2009 | Original Contribution

Effect of CLA isomers and their mixture on aging C57Bl/6J mice

Authors: Ganesh V. Halade, Md. M. Rahman, Gabriel Fernandes

Published in: European Journal of Nutrition | Issue 7/2009

Abstract

Background

Dietary supplements containing conjugated linoleic acid (CLA) are widely promoted for weight loss management over the counter. Recently, FDA approved the CLA as Generally Recognized as Safe category so that it can be used in various food and beverages. The combined effect of CLA isomers have been studied extensively in animals and humans, however, the role of individual isomers remains unraveled.

Aim

The present investigation addresses the effects of CLA isomers on body composition and body weight as well as safety using female C57Bl/6J aging mice.

Methods

Two main CLA isomers and their mixture were fed to 12-months-old female C57Bl/6J mice. Ten percent corn oil (CO) based fat diet supplemented with 0.5% purified cis 9 trans 11 (c9,t11) CLA or trans 10 cis 12 (t10,c12) CLA or their mixture (CLA mix, 50:50) for 6 months. The lean mass, fat mass, glucose, non-esterified fatty acids, and insulin were examined at the end of study.

Results

As a result of 6 months dietary intervention, both t10,c12 CLA and CLA mix groups showed increased lean mass and reduced fat mass compared to that of c9,t11 CLA and CO group. However, insulin resistance and liver hypertrophy were observed in t10,c12 CLA and CLA mix groups based on the results of homeostasis model assessment, revised quantitative insulin-sensitivity check index (R-QUICKI), intravenous glucose tolerance test, and liver histology. Liver histology revealed that increased liver weight was due to hypertrophy.

Conclusion

In conclusion, the major CLA isomers have a distinct effect on fat mass, glucose, and insulin metabolism. The t10,c12 isomer was found to reduce the fat mass and to increase the lean mass but significantly contributed to increase insulin resistance and liver hypertrophy, whereas c9,t11 isomer prevented the insulin resistance. Between the two major CLA isomers, the t10,c12 was attributed to reduce fat mass whereas, c9,t11 improves the insulin sensitivity.

Akahoshi A, Goto Y, Murao K, Miyazaki T, Yamasaki M, Nonaka M, Yamada K, Sugano M (2002) Conjugated linoleic acid reduces body fats and cytokine levels of mice. Biosci Biotechnol Biochem 66:916–920CrossRef

Azain MJ, Hausman DB, Sisk MB, Flatt WP, Jewell DE (2000) Dietary conjugated linoleic acid reduces rat adipose tissue cell size rather than cell number. J Nutr 130:1548–1554

Bhattacharya A, Banu J, Rahman M, Causey J, Fernandes G (2006) Biological effects of conjugated linoleic acids in health and disease. J Nutr Biochem 17:789–810CrossRef

Bhattacharya A, Rahman MM, McCarter R, O’Shea M, Fernandes G (2006) Conjugated linoleic acid and chromium lower body weight and visceral fat mass in high-fat-diet-fed mice. Lipids 41:437–444CrossRef

Bhattacharya A, Rahman MM, Sun D, Lawrence R, Mejia W, McCarter R, O’Shea M, Fernandes G (2005) The combination of dietary conjugated linoleic acid and treadmill exercise lowers gain in body fat mass and enhances lean body mass in high fat-fed male Balb/C mice. J Nutr 135:1124–1130

Brodie AE, Manning VA, Ferguson KR, Jewell DE, Hu CY (1999) Conjugated linoleic acid inhibits differentiation of pre- and post- confluent 3T3–L1 preadipocytes but inhibits cell proliferation only in preconfluent cells. J Nutr 129:602–606

Cesari M, Kritchevsky SB, Baumgartner RN, Atkinson HH, Penninx BW, Lenchik L, Palla SL, Ambrosius WT, Tracy RP, Pahor M (2005) Sarcopenia, obesity, and inflammation—results from the trial of angiotensin converting enzyme inhibition and novel cardiovascular risk factors study. Am J Clin Nutr 82:428–434

DeLany JP, Blohm F, Truett AA, Scimeca JA, West DB (1999) Conjugated linoleic acid rapidly reduces body fat content in mice without affecting energy intake. Am J Physiol 276:R1172–R1179

Despres JP, Nadeau A, Tremblay A, Ferland M, Moorjani S, Lupien PJ, Theriault G, Pinault S, Bouchard C (1989) Role of deep abdominal fat in the association between regional adipose tissue distribution and glucose tolerance in obese women. Diabetes 38:304–309CrossRef

10.

Dirks AJ, Leeuwenburgh C (2006) Tumor necrosis factor alpha signaling in skeletal muscle: effects of age and caloric restriction. J Nutr Biochem 17:501–508CrossRef

11.

Field CJ, Ryan EA, Thomson AB, Clandinin MT (1990) Diet fat composition alters membrane phospholipid composition, insulin binding, and glucose metabolism in adipocytes from control and diabetic animals. J Biol Chem 265:11143–11150

12.

Ha YL, Grimm NK, Pariza MW (1987) Anticarcinogens from fried ground beef: heat-altered derivatives of linoleic acid. Carcinogenesis 8:1881–1887CrossRef

13.

Ha YL, Storkson J, Pariza MW (1990) Inhibition of benzo(a)pyrene-induced mouse forestomach neoplasia by conjugated dienoic derivatives of linoleic acid. Cancer Res 50:1097–1101

14.

Hargrave KM, Meyer BJ, Li C, Azain MJ, Baile CA, Miner JL (2004) Influence of dietary conjugated linoleic acid and fat source on body fat and apoptosis in mice. Obes Res 12:1435–1444CrossRef

15.

http://www.nutraingredients-usa.com/Industry/CLA-achieves-US-approval-for-use-in-foods

16.

Inoue N, Nagao K, Hirata J, Wang YM, Yanagita T (2004) Conjugated linoleic acid prevents the development of essential hypertension in spontaneously hypertensive rats. Biochem Biophys Res Commun 323:679–684CrossRef

17.

Ip C, Singh M, Thompson HJ, Scimeca JA (1994) Conjugated linoleic acid suppresses mammary carcinogenesis and proliferative activity of the mammary gland in the rat. Cancer Res 54:1212–1215

18.

Kelley DS, Simon VA, Taylor PC, Rudolph IL, Benito P, Nelson GJ, Mackey BE, Erickson KL (2001) Dietary supplementation with conjugated linoleic acid increased its concentration in human peripheral blood mononuclear cells, but did not alter their function. Lipids 36:669–674CrossRef

19.

Kelley DS, Warren JM, Simon VA, Bartolini G, Mackey BE, Erickson KL (2002) Similar effects of c9, t11-CLA and t10, c12-CLA on immune cell functions in mice. Lipids 37:725–728CrossRef

20.

Kepler CR, Hirons KP, McNeill JJ, Tove SB (1966) Intermediates and products of the biohydrogenation of linoleic acid by Butyrinvibrio fibrisolvens. J Biol Chem 241:1350–1354

21.

Kissebah AH (1991) Insulin resistance in visceral obesity. Int J Obes 15(Suppl 2):109–115

22.

Larsen TM, Toubro S, Astrup A (2003) Efficacy and safety of dietary supplements containing CLA for the treatment of obesity: evidence from animal and human studies. J Lipid Res 44:2234–2241CrossRef

23.

Larsen TM, Toubro S, Gudmundsen O, Astrup A (2006) Conjugated linoleic acid supplementation for 1 y does not prevent weight or body fat regain. Am J Clin Nutr 83:606–612

24.

Lee KN, Kritchevsky D, Pariza MW (1994) Conjugated linoleic acid and atherosclerosis in rabbits. Atherosclerosis 108:19–25CrossRef

25.

Lin H, Boylston TD, Chang MJ, Luedecke LO, Shultz TD (1995) Survey of the conjugated linoleic acid contents of dairy products. J Dairy Sci 78:2358–2365CrossRef

26.

Liu S, Baracos VE, Quinney HA, Clandinin MT (1994) Dietary omega-3 and polyunsaturated fatty acids modify fatty acyl composition and insulin binding in skeletal-muscle sarcolemma. Biochem J 299(Pt 3):831–837

27.

Maffei M, Halaas J, Ravussin E, Pratley RE, Lee GH, Zhang Y, Fei H, Kim S, Lallone R, Ranganathan S et al (1995) Leptin levels in human and rodent: measurement of plasma leptin and ob RNA in obese and weight-reduced subjects. Nat Med 1:1155–1161CrossRef

28.

Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC (1985) Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 28:412–419CrossRef

29.

Medina EA, Horn WF, Keim NL, Havel PJ, Benito P, Kelley DS, Nelson GJ, Erickson KL (2000) Conjugated linoleic acid supplementation in humans: effects on circulating leptin concentrations and appetite. Lipids 35:783–788CrossRef

30.

Miller CC, Park Y, Pariza MW, Cook ME (1994) Feeding conjugated linoleic acid to animals partially overcomes catabolic responses due to endotoxin injection. Biochem Biophys Res Commun 198:1107–1112CrossRef

31.

Moulias R, Meaume S, Raynaud-Simon A (1999) Sarcopenia, hypermetabolism, and aging. Z Gerontol Geriatr 32:425–432CrossRef

32.

Ohashi A, Matsushita Y, Kimura K, Miyashita K, Saito M (2004) Conjugated linoleic acid deteriorates insulin resistance in obese/diabetic mice in association with decreased production of adiponectin and leptin. J Nutr Sci Vitaminol (Tokyo) 50:416–421

33.

Ostrowska E, Muralitharan M, Cross RF, Bauman DE, Dunshea FR (1999) Dietary conjugated linoleic acids increase lean tissue and decrease fat deposition in growing pigs. J Nutr 129:2037–2042

34.

Park Y, Albright KJ, Liu W, Storkson JM, Cook ME, Pariza MW (1997) Effect of conjugated linoleic acid on body composition in mice. Lipids 32:853–858CrossRef

35.

Park Y, Storkson JM, Albright KJ, Liu W, Pariza MW (1999) Evidence that the trans-10, cis-12 isomer of conjugated linoleic acid induces body composition changes in mice. Lipids 34:235–241CrossRef

36.

Perseghin G, Caumo A, Caloni M, Testolin G, Luzi L (2001) Incorporation of the fasting plasma FFA concentration into QUICKI improves its association with insulin sensitivity in nonobese individuals. J Clin Endocrinol Metab 86:4776–4781CrossRef

37.

Rahman MM, Bhattacharya A, Banu J, Fernandes G (2007) Conjugated linoleic acid protects against age-associated bone loss in C57BL/6 female mice. J Nutr Biochem 18:467–474CrossRef

38.

Riserus U, Arner P, Brismar K, Vessby B (2002) Treatment with dietary trans10cis12 conjugated linoleic acid causes isomer-specific insulin resistance in obese men with the metabolic syndrome. Diabetes Care 25:1516–1521CrossRef

39.

Riserus U, Basu S, Jovinge S, Fredrikson GN, Arnlov J, Vessby B (2002) Supplementation with conjugated linoleic acid causes isomer-dependent oxidative stress and elevated C-reactive protein: a potential link to fatty acid-induced insulin resistance. Circulation 106:1925–1929CrossRef

40.

Roche HM, Noone E, Sewter C, Mc Bennett S, Savage D, Gibney MJ, O’Rahilly S, Vidal-Puig AJ (2002) Isomer-dependent metabolic effects of conjugated linoleic acid: insights from molecular markers sterol regulatory element-binding protein-1c and LXRalpha. Diabetes 51:2037–2044CrossRef

41.

Ryder JW, Portocarrero CP, Song XM, Cui L, Yu M, Combatsiaris T, Galuska D, Bauman DE, Barbano DM, Charron MJ, Zierath JR, Houseknecht KL (2001) Isomer-specific antidiabetic properties of conjugated linoleic acid. Improved glucose tolerance, skeletal muscle insulin action, and UCP-2 gene expression. Diabetes 50:1149–1157CrossRef

42.

Shepherd PR, Kahn BB (1999) Glucose transporters and insulin action-implications for insulin resistance and diabetes mellitus. N Engl J Med 341:248–257CrossRef

43.

Staiger H, Haring HU (2005) Adipocytokines: fat-derived humoral mediators of metabolic homeostasis. Exp Clin Endocrinol Diabetes 113:67–79CrossRef

44.

Sun D, Krishnan A, Zaman K, Lawrence R, Bhattacharya A, Fernandes G (2003) Dietary n-3 fatty acids decrease osteoclastogenesis and loss of bone mass in ovariectomized mice. J Bone Miner Res 18:1206–1216CrossRef

45.

Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN (1988) Diet-induced type II diabetes in C57BL/6 J mice. Diabetes 37:1163–1167CrossRef

46.

Tsuboyama-Kasaoka N, Takahashi M, Tanemura K, Kim HJ, Tange T, Okuyama H, Kasai M, Ikemoto S, Ezaki O (2000) Conjugated linoleic acid supplementation reduces adipose tissue by apoptosis and develops lipodystrophy in mice. Diabetes 49:1534–1542CrossRef

47.

Wallace TM, Levy JC, Matthews DR (2004) An increase in insulin sensitivity and basal beta-cell function in diabetic subjects treated with pioglitazone in a placebo-controlled randomized study. Diabet Med 21:568–576CrossRef

48.

Wang YC, Colditz GA, Kuntz KM (2007) Forecasting the obesity epidemic in the aging U.S. population. Obesity (Silver Spring) 15(285):5–2865

49.

West DB, Delany JP, Camet PM, Blohm F, Truett AA, Scimeca J (1998) Effects of conjugated linoleic acid on body fat and energy metabolism in the mouse. Am J Physiol 275:R667–R672

50.

Whigham LD, Cook ME, Atkinson RL (2000) Conjugated linoleic acid: implications for human health. Pharmacol Res 42:503–510CrossRef

51.

Whigham LD, O’Shea M, Mohede IC, Walaski HP, Atkinson RL (2004) Safety profile of conjugated linoleic acid in a 12-month trial in obese humans. Food Chem Toxicol 42:1701–1709CrossRef

52.

Winzell MS, Ahren B (2004) The high-fat diet-fed mouse: a model for studying mechanisms and treatment of impaired glucose tolerance and type 2 diabetes. Diabetes 53(Suppl 3):S215–S219CrossRef

53.

Yamasaki M, Ikeda A, Oji M, Tanaka Y, Hirao A, Kasai M, Iwata T, Tachibana H, Yamada K (2003) Modulation of body fat and serum leptin levels by dietary conjugated linoleic acid in Sprague-Dawley rats fed various fat-level diets. Nutrition 19:30–35CrossRef

54.

Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, Hara K, Mori Y, Ide T, Murakami K, Tsuboyama-Kasaoka N, Ezaki O, Akanuma Y, Gavrilova O, Vinson C, Reitman ML, Kagechika H, Shudo K, Yoda M, Nakano Y, Tobe K, Nagai R, Kimura S, Tomita M, Froguel P, Kadowaki T (2001) The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 7:941–946CrossRef

55.

Yu Y, Correll PH, Vanden Heuvel JP (2002) Conjugated linoleic acid decreases production of pro-inflammatory products in macrophages: evidence for a PPAR gamma-dependent mechanism. Biochim Biophys Acta 1581:89–99

56.

Zamboni M, Mazzali G, Fantin F, Rossi A, Di Francesco V (2008) Sarcopenic obesity: a new category of obesity in the elderly. Nutr Metab Cardiovasc Dis 18:388–395CrossRef

57.

Zamboni M, Mazzali G, Zoico E, Harris TB, Meigs JB, Di Francesco V, Fantin F, Bissoli L, Bosello O (2005) Health consequences of obesity in the elderly: a review of four unresolved questions. Int J Obes (Lond) 29:1011–1029CrossRef

Title: Effect of CLA isomers and their mixture on aging C57Bl/6J mice
Authors: Ganesh V. Halade
Md. M. Rahman
Gabriel Fernandes
Publication date: 01-10-2009
Publisher: D. Steinkopff-Verlag
Published in: European Journal of Nutrition / Issue 7/2009
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-009-0029-7

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