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AB0195 THE IMPACT OF KETOGENIC DIET AND HIGH-FAT-HIGH-GLUCOSE DIET IN PRISTANE INDUCED LUPUS-LIKE NEPHRITIS MURINE MODEL
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  1. Chao-Yi Wu1,
  2. Huang-Yu Yang2,
  3. Jing-Long Haung1
  1. 1Linkou Chang Gung Memorial Hospital Hospital, Department of Pediatrics. Division of Allergy, Asthma, and Rheumatology, Taoyuan city, Taiwan, Republic of China
  2. 2Linkou Chang Gung Memorial Hospital Hospital, Department of Nephrology, Taoyuan city, Taiwan, Republic of China

Abstract

Background Systemic lupus erythematous is a chronic systemic inflammatory disease which commonly involes kidneys[1]. Aside from the use of conventional immunosuppressants, dietary components and metabolites may likely affect our immune system.

Objectives An interest in the anti-inflammatory property of ketogenic diet (KD) has recently come to attention.

It not only alters the balance between Th17 and Treg cells[2], its metabolite, beta-hydroxybutyrate was known to block NLRP3 inflammasome-mediated inflammation[3-6]. High-fat-high-glucose diet (HFGD), on the other hand, was known for a proinflammatory property. Aim to understand the immune modulatory effect of KD and HFGD in cases with systemic lupus erythematous, a chronic systemic inflammatory disease with glomerulonephritis, pristane induce lupus like nephritis murine model was used.

Methods Pristane induced lupus nephritis mice were divided in to groups fed with regular chow (CD), KD and HFGD along with healthy controls. The diets were kept for 6 months with regular body weight and urine protein monitoring. Serum samples were collected for metabolic evaluation and immune survey bimonthly. The mice were sacrificed 6 months after diet change. Kidneys, lymph nodes, spleen, blood and guts were collected for evaluation.

Results KD and HFGD were both well tolerated by experimental mice. Two months after diet change, higher level of beta-hydroxybutyrate and triglyceride but lower sugar level was noted in mice fed on KD when compared to those fed on CD and HFGD (all p<0.05). Mice fed on KD and HFGD have a much lower RBC and platelet count than those fed on CD in the experimental mice group (both p<0.05). Although global lymphocyte counts were much lower in those pristine treated mice, Th17 lymphocytes were significantly higher in the blood as well as kidneys among those fed on HFGD (all p<0.05). This is compatible with their high serum concentration of anti-dsDNA, anti-nRNP and anti-Sm and the rapid progressing proteinuria. Renal, hepatic and intestinal histopathology was still under analysis at present.

Conclusion In conclusion, food plays a critical role in immune modification. Despite the reported anti-inflammatory effect of KD, it does not mitigate lupus nephritis progression. HFGD formula, however, accelerated the autoimmune phenotype for cases with lupus like glomerulonephritis.

References [1] Borchers AT, Leibushor N, Naguwa SM, Cheema GS, Shoenfeld Y, Gershwin ME (2012) Lupus nephritis: a critical review. Autoimmun Rev12:174-194.

[2] Ni FF, Li CR, Liao JX, Wang GB, Lin SF, Xia Y, Wen JL (2016) The effects of ketogenic diet on the Th17/Treg cells imbalance in patients with intractable childhood epilepsy. Seizure38:17-22.

[3] Goldberg EL, Asher JL, Molony RD, Shaw AC, Zeiss CJ, Wang C, Morozova-Roche LA, Herzog RI, Iwasaki A, Dixit VD (2017) beta-Hydroxybutyrate Deactivates Neutrophil NLRP3 Inflammasome to Relieve Gout Flares. Cell Rep18:2077-2087.

[4] Choi IY, Piccio L, Childress P, Bollman B, Ghosh A, Brandhorst S, Suarez J, Michalsen A, Cross AH, Morgan TE, Wei M, Paul F, Bock M, Longo VD (2016) A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms. Cell Rep15:2136-2146.

[5] Storoni M, Plant GT (2015) The Therapeutic Potential of the Ketogenic Diet in Treating Progressive Multiple Sclerosis. Mult Scler Int2015:681289.

[6] Choi IY, Lee C, Longo VD (2017) Nutrition and fasting mimicking diets in the prevention and treatment of autoimmune diseases and immunosenescence. Mol Cell Endocrinol455:4-12.

Disclosure of Interests None declared

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