Skip to main content
Log in

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

  • Original Contribution
  • Published:
European Journal of Nutrition Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. 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 66:916–920

    Article  CAS  Google Scholar 

  2. 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

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  4. 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 41:437–444

    Article  CAS  Google Scholar 

  5. 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

    CAS  Google Scholar 

  6. 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

    CAS  Google Scholar 

  7. 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

    CAS  Google Scholar 

  8. 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

    CAS  Google Scholar 

  9. 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 38:304–309

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

  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 12:1435–1444

    Article  CAS  Google Scholar 

  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 323:679–684

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

  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 36:669–674

    Article  CAS  Google Scholar 

  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 37:725–728

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  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 44:2234–2241

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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 78:2358–2365

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

  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 1:1155–1161

    Article  CAS  Google Scholar 

  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 28:412–419

    Article  CAS  Google Scholar 

  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 35:783–788

    Article  CAS  Google Scholar 

  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 198:1107–1112

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

  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

    CAS  Google Scholar 

  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 32:853–858

    Article  CAS  Google Scholar 

  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 34:235–241

    Article  CAS  Google Scholar 

  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 86:4776–4781

    Article  CAS  Google Scholar 

  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 18:467–474

    Article  CAS  Google Scholar 

  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 25:1516–1521

    Article  CAS  Google Scholar 

  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 106:1925–1929

    Article  CAS  Google Scholar 

  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 51:2037–2044

    Article  CAS  Google Scholar 

  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 50:1149–1157

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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 18:1206–1216

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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 49:1534–1542

    Article  CAS  Google Scholar 

  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 21:568–576

    Article  CAS  Google Scholar 

  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

    Google Scholar 

  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

    CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  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 42:1701–1709

    Article  CAS  Google Scholar 

  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–S219

    Article  Google Scholar 

  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 19:30–35

    Article  CAS  Google Scholar 

  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 7:941–946

    Article  CAS  Google Scholar 

  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

    CAS  Google Scholar 

  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 18:388–395

    Article  CAS  Google Scholar 

  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) 29:1011–1029

    Article  CAS  Google Scholar 

Download references

Acknowledgment

The authors would like to thank Paul J Williams for his critical review of this manuscript and to Nishu Kazi for her help in diet preparation, animal feeding, and care. This work was supported by NIH grant R21 AG027562.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gabriel Fernandes.

Additional information

G. V. Halade and Md. M. Rahman contributed equally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Halade, G.V., Rahman, M.M. & Fernandes, G. Effect of CLA isomers and their mixture on aging C57Bl/6J mice. Eur J Nutr 48, 409–418 (2009). https://doi.org/10.1007/s00394-009-0029-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00394-009-0029-7

Keywords

Navigation