(OR18-03-23) Maternal Methyl Donor Nutrients Supplementation to a High-Fat High-Sucrose Diet Modulates Systemic Vitamin D Signaling and Renal Inflammation Among Adult Offspring

Objectives: Systemic activation of vitamin D receptor (VDR) has shown to lower inflammatory status in chronic kidney disease patients. Obesogenic maternal diet may increase risks of renal and metabolic injury in adult offspring. Previously, we found that methyl-donor nutrients (MS) supplementation normalized vitamin D (VD) status and attenuated systemic inflammation induced by maternal high-fat high-sugar (HFS) diet among offspring. Here, we investigate if MS-supplemented HFS diet during pregnancy and lactation can modulate renal VDR signaling and inflammation in adult offspring rats.

Methods: During pregnancy and lactation, 10-week-old Sprague-Dawley rats (n = 10/group) were randomly assigned to either control (CON), CON supplemented with MS (CON-MS), HFS, or HFS supplemented with MS (HFS-MS). At weaning (21 days), offspring (n = 6/group/sex) were randomized to receive either CON (P-CON) or HFS (P-HFS) diet until sacrifice (15 weeks). Serum and kidneys were collected for analysis.<

Results: Serum 1,25-dihydroxyvitamin D (1,25D) levels in pups born to HFS and HFS-MS dams were 39% (P < 0.01) and 50% (P < 0.01) higher, respectively, than CON offspring, with no effect from postnatal diet. Compared to CON offspring, mRNA levels of renal vdr were 50% lower (P < 0.01) in HFS offspring, but did not differ from HFS-MS offspring. Unlike VDR signaling, both pre- and postnatal diets significantly impacted pro-inflammatory signaling, specifically with P-HFS pups, in which mRNA expressions of tlr4, Il-1β, and Il-6 were downregulated by 2.4-, 2.3-, and 3-fold, respectively, when compared to P-CON pups born to HFS-MS dams. A negative correlation was found between renal vdr and tlr4 mRNA expressions (r = -0.231; P = 0.046).

Conclusions: Renal activation of VDR in offspring was driven by prenatal diets and was not modified by MS supplementation. Prenatal MS supplementation to a HFS diet, however, may alleviate renal inflammation in offspring, a phenotype that could be dependent on postnatal diets. Further research will focus on mechanisms underlying the role of MS in regulating systemic VD signaling, also the interactions between VDR and TLR4 during progression of renal inflammation under an obesogenic condition.

Funding Sources: Texas State University startup funds to Dr. Gar Yee Koh and Dr. Jie Zhu, and indirect cost return fund to Dr. Michelle Lane.