Systemic lupus erythematosus (SLE) is an autoimmune disease affecting over 1 million Americans, mostly women, which is influenced by both genetic and environmental risk factors and shortens the life span. Its clinical features include glomerulonephritis, cardiovascular disease (CVD), skin rashes, serositis, hemolytic anemia, impairment of the central nervous system and bone loss. Several animal models are in use to study SLE including NZB x NZW F1 (B/W) and MRL/lpr mice. We have demonstrated that ad libitum (AL) food intake with n-6 fatty acids (corn oil) enriched in 18:2 linoleic acid (LA) promotes rapid development of SLE in both strains of mice including bone loss in MRL/lpr mice. Although feeding AL a regular fish oil containing 22- 30% EPA/DHA (20:5 + 22:6) n-3 fatty acids provides some benefit, calorie restriction (CR) alone significantly delayed the onset of the disease. We recently noted, however, that concentrated fish oil (EPA/DHA 50%) when fed AL protects against kidney disease similar to CR. Concentrated n-3 fatty acid (FA) supplementation was able to inhibit the increase in NF-kB, and co-stimulatory molecules, and increase antioxidant enzymes in target tissues resulting in a decrease of proinflammatory IL-18 cytokine. We now hypothesize that recently available through prescription, OMACOR fish oil (EPA/DHA 90%), to treat hyperglyceridemic patients, will reduce pro-inflammatory cytokines from macrophages and T cells, thereby preventing or delaying the onset of autoimmune disease. The proposed new studies in specific aim 1 is to establish the minimal dose of OMACOR fish oil required to suppress renal disease and prolong maximal lifespan in B/W and MRL/lpr mice;
Specific aim 2 is to determine the changes in anti- and pro-inflammatory cytokines, NF-kB expression and other signaling pathways in macrophages and T cells of B/W and MRL/lpr mice fed OMACOR fish oil;
Specific aim 3 is to determine the interaction of OMACOR n-3 fatty acids along with immunosuppressive cyclophosphamide and methylprednisolone drug therapy after the onset of SLE in controlling renal disease and bone loss in MRL/lpr mice. These new studies with FDA approved OMACOR n-3 FA will establish its efficacy against renal disease and bone loss alone, or in combination with immunosuppressive drugs. The proposed studies will also help to gain insight to undertake clinical studies to prevent renal and CVD as well as bone loss in SLE patients.

Agency
National Institute of Health (NIH)
Institute
National Center for Complementary & Alternative Medicine (NCCAM)
Type
Research Project (R01)
Project #
5R01AT004259-05
Application #
8214697
Study Section
Special Emphasis Panel (ZRG1-BDA-C (03))
Program Officer
Pontzer, Carol H
Project Start
2008-01-01
Project End
2014-05-31
Budget Start
2011-12-01
Budget End
2014-05-31
Support Year
5
Fiscal Year
2012
Total Cost
$323,433
Indirect Cost
$105,633
Name
University of Texas Health Science Center San Antonio
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
800772162
City
San Antonio
State
TX
Country
United States
Zip Code
78229
Halade, Ganesh V; Williams, Paul J; Veigas, Jyothi M et al. (2013) Concentrated fish oil (Lovaza(R)) extends lifespan and attenuates kidney disease in lupus-prone short-lived (NZBxNZW)F1 mice. Exp Biol Med (Maywood) 238:610-22
Banu, Jameela; Varela, Erika; Guerra, Juan M et al. (2012) Dietary coral calcium and zeolite protects bone in a mouse model for postmenopausal bone loss. Nutr Res 32:965-75
Veigas, Jyothi M; Williams, Paul J; Halade, Ganesh et al. (2011) Fish oil concentrate delays sensitivity to thermal nociception in mice. Pharmacol Res 63:377-82
Halade, Ganesh V; El Jamali, Amina; Williams, Paul J et al. (2011) Obesity-mediated inflammatory microenvironment stimulates osteoclastogenesis and bone loss in mice. Exp Gerontol 46:43-52
Halade, Ganesh V; Rahman, Md M; Williams, Paul J et al. (2011) Combination of conjugated linoleic acid with fish oil prevents age-associated bone marrow adiposity in C57Bl/6J mice. J Nutr Biochem 22:459-69
Halade, Ganesh V; Williams, Paul J; Lindsey, Merry L et al. (2011) Fish oil decreases inflammation and reduces cardiac remodeling in rosiglitazone treated aging mice. Pharmacol Res 63:300-7
Halade, Ganesh V; Rahman, Md M; Fernandes, Gabriel (2010) Differential effects of conjugated linoleic acid isomers in insulin-resistant female C57Bl/6J mice. J Nutr Biochem 21:332-7
Banu, Jameela; Bhattacharya, Arunabh; Rahman, Mizanur et al. (2010) Endogenously produced n-3 fatty acids protect against ovariectomy induced bone loss in fat-1 transgenic mice. J Bone Miner Metab 28:617-26
Halade, Ganesh V; Rahman, Md Mizanur; Bhattacharya, Arunabh et al. (2010) Docosahexaenoic acid-enriched fish oil attenuates kidney disease and prolongs median and maximal life span of autoimmune lupus-prone mice. J Immunol 184:5280-6
Halade, Ganesh V; Rahman, Md M; Williams, Paul J et al. (2010) High fat diet-induced animal model of age-associated obesity and osteoporosis. J Nutr Biochem 21:1162-9

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