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Diallyl trisulfide improves kidney function through alteration of fatty acid receptor expression in diabetic mice
Author(s) -
Weber Gregory,
Pushpakumar Sathnur,
Sen Utpal
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.567.17
Subject(s) - diallyl trisulfide , diabetic nephropathy , kidney , endocrinology , renal function , medicine , receptor , chemistry , diabetes mellitus , population , pharmacology , biology , biochemistry , apoptosis , environmental health
Approximately 10% of the United States population suffers from diabetes causing diabetic nephropathy (DN) and eventually leading to renal failure. Fatty acids (FAs) are byproducts of gut microbiota and can regulate physiological process such as metabolism and inflammation as well as influenced through dietary supplements. Certain FA receptors have been shown to exert anti‐inflammatory effects in diabetes and other diseases; however, the role of these receptors in the kidney is not well defined. Diallyl trisulfide (DATS) is a major organosulfur component of garlic and is metabolized into hydrogen sulfide, an important gasotransmitter with noted cardiovascular and renal benefits. Whether DATS regulates FAs and their receptors in the kidney is unclear. In this study, we sought to determine if dietary supplementation with DATS improves kidney function by reducing inflammation through FA receptors in a Type‐II diabetic mouse model. Initial results showed improved kidney function of diabetic mice supplemented with DATS, as evidenced by an increase in glomerular filtration rate (GFR) as well as a lower resistive index (RI) of the renal artery compared to diabetic mice on a normal diet. The expression of short chain fatty acid receptor Gpr43 and long chain fatty acid receptor Gpr120 was altered in kidney of mice given DATS compared to untreated animals. In addition, Ptgs2, an enzyme implicated in the inflammatory response and can be inhibited by some naturally occurring FAs, was reduced in the kidney of diabetic mice supplemented with DATS. 16S sequencing showed DATS supplementation affected host gut microbiome composition, showing an enrichment in Verrucomicrobia and increased alpha diversity in diabetic mice on DATS diet. In conclusion, our data suggests FA receptors may play a role in the diabetic kidney by reducing inflammation with DATS supplementation, influencing the expression of these receptors, and improving kidney function. Further, a shift in the gut microbiome of diabetic mice toward that of non‐diabetic mice suggests a role for gut microbiota in DN and DATS supplementation may help delay or prevent the onset of this disease. Support or Funding Information This study was supported in part by U.S. National Institutes of Health (NIH) Grant DK104653 (U.S.) and American Heart Association Scientist Development Grant 15SDG25840013 (S.P.). This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .