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Dietary Conjugated Linoleic Acid-c9t11 Prevents Collagen-Induced Arthritis, Whereas Conjugated Linoleic Acid-t10c12 Increases Arthritic Severity

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Lipids

Abstract

Two conjugated linoleic acid (CLA) isomers, cis-9, trans-11 (CLAc9t11) and trans-10, cis-12 (CLAt10c12), reduce inflammation in a number of animal models, including collagen-induced arthritis (CA). However, little is known about the ability of individual CLA isomers to prevent autoimmune disease onset. Evidence that mixed isomer CLA drives T helper cell (Th) 1 responses suggests that CLA, or a specific isomer, exacerbates onset of Th1 autoimmune diseases. In two experiments, we examined if prior dietary exposure to CLAt10c12 (experiment 1) or CLAc9t11 (experiment 2) affected the incidence or severity of CA. DBA/1 mice were fed a semi purified diet with either 6% corn oil (CO, w/w), 5.75% CO plus 0.25% CLAt10c12, or 5.5% CO plus 0.5% CLAc9t11 prior to arthritis development. Arthritis incidence and severity, anti-collagen antibodies, paw cytokines, and hepatic fatty acids were measured. CLAt10c12 had no effect on arthritis incidence but increased arthritic severity (42%, P = 0.02); however, CLAc9t11 decreased arthritis incidence 39% compared to CO fed mice (P = 0.01), but had no effect on disease severity. CLAt10c12-induced increase in anti-collagen type II IgG antibodies may be a mechanism by which this isomer increased arthritic severity, and CLAc9t11-induced increase in Th2 paw cytokines (IL-4 and IL-10, P ≤ 0.04) may explain how CLAc9t11 reduced the arthritis incidence. While both isomers are well known to reduce inflammation in arthritic mice, these new data suggest isomer differences when fed prior to autoimmune disease.

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Abbreviations

CLA:

Conjugated linoleic acid

CLAt10c12:

Conjugated linoleic acid trans-10, cis-12

Th:

T helper cell type

CLAc9t11:

Conjugated linoleic acid cis-9, trans-11

CA:

Collagen-induced arthritis

CO:

Corn oil

NF-κB:

Nuclear factor-kappa B

TNF:

Tumor necrosis factor

CII:

Collagen type II

Ig:

Immunoglobulin

2°:

Secondary

AD:

Days post arthritis development

ND:

Chick CII injected but no arthritis development

CAS:

Clinical arthritic score

IL:

Interleukin

IFN:

Interferon

FAME:

Fatty acid methyl esters

NZB/W F1:

F1 hybrid of New Zealand Black and White cross

SCD:

Stearoyl-CoA desaturase

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Acknowledgements

The authors thank Dawn Irish, Angel Guterriez-Velin, and Terry Jobsis for their assistance with animal husbandry. The authors would like to thank Peter Crump for his assistance with statistical analyses. This research was partially supported by a USDA Hatch Project Grant (MSN130802), patent royalties from the Wisconsin Alumni Research Foundation (WARF), unrestricted gifts from BASF, the Natural Health Research Institute Scholarship for Arthritis from the American Oil Chemists Society, and the College of Agricultural and Life Sciences at the University of Wisconsin-Madison.

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Authors and Affiliations

  1. Molecular and Environmental Toxicology Center, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Jessica A. Muhlenbeck & Mark E. Cook

  2. Department of Animal Sciences, University of Wisconsin-Madison, Madison, WI, 53706, USA

    Daniel E. Butz, Jake M. Olson, Daniela Uribe-Cano & Mark E. Cook

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  1. Jessica A. Muhlenbeck
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  2. Daniel E. Butz
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Correspondence to Mark E. Cook.

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Muhlenbeck, J.A., Butz, D.E., Olson, J.M. et al. Dietary Conjugated Linoleic Acid-c9t11 Prevents Collagen-Induced Arthritis, Whereas Conjugated Linoleic Acid-t10c12 Increases Arthritic Severity. Lipids 52, 303–314 (2017). https://doi.org/10.1007/s11745-017-4241-6

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