AB0195 THE IMPACT OF KETOGENIC DIET AND HIGH-FAT-HIGH-GLUCOSE DIET IN PRISTANE INDUCED LUPUS-LIKE NEPHRITIS MURINE MODEL
Authors: Chao-Yi Wu, Huang-Yu Yang, Jing-Long Haung
Journal: Annals of the Rheumatic Diseases (2019)

<h3>Background</h3> 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. <h3>Objectives</h3> 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. <h3>Methods</h3> 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. <h3>Results</h3> 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&lt;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&lt;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&lt;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. <h3>Conclusion</h3> 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. <h3>References</h3> [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. <h3>Disclosure of Interests</h3> None declared