High Fat Diet With Normal Salt Feeding Does Not Change Renal m-TORC Signaling Activities In Male And Female Dahl Salt Sensitive Rats.

We have previously reported that high fat diet (HFD) with normal salt feeding strongly promotes hypertension in both male and female Dahl salt sensitive (SS) rats. Only males, however, exhibit hypertension-associated renal inflammation/injury. The underlying mechanisms responsible for sex differences in HFD associated renal inflammation/injury are undetermined. It has been reported that increased activity of Mammalian Target of Rapamycin Complex 1/2 (mTORC) contribute to high salt diet associated hypertension and renal inflammation/injury in Dahl SS male rats. In this study, we determined whether HFD increases renal mTORC signaling in Dahl SS rats and if there are sex differences in signaling. Renal cortex and medulla were collected from rats fed a control diet (CD, 10% kcal fat) or a HFD (60% kcal fat) with 0.3% NaCl for 10, 17 or 24 weeks (WKs, starting at weaning, the time points correspond to pre-hypertension, developing hypertension and established hypertension phases of the model. Ratio (%) of expression of phospho-S6 ribosomal protein Ser235/236 (pS6)/S6 (a marker for mTORC1), and phospho-AKT Ser473 (pAKT)/AKT (a marker for mTORC2) were used to evaluate mTORC activity. The activity of mTORC1 in CD male cortex and female medulla were slightly increased at 17 and 24WKs of feeding compared to 10 WKs (22±4 and 16±7 vs 2±2, P<0.05), but HFD did not change the activity in cortex and medulla significantly in males (cortex,10±5, 14±5, 20±5; medulla 9±2, 18±6, 25±12) or females (cortex, 4±1, 12±3, 13±2; medulla 13±8, 22±8, 24±16) (P>0.5). The overall activity of mTORC2 in CD males and females were very low and mostly unchanged during 24WKs feeding, except for a slight increase in CD male cortex at 17WKs of feeding compared to 10WKs (4±1 vs 0.1±0.02, P<0.05). HFD caused only a slight increase of mTORC2 in medulla from males (4±1 vs 1±0.5) and a decrease in medulla from females (8±2 vs 0.9±0.3) (P<0.05) at 24WKs compared with 10WKs of feeding. Overall HFD did not cause marked changes in renal mTORC1/2 signaling activities. In addition, there were no significant differences in mTORC signaling activities between males and females. Therefore mTORC signaling pathways are not likely to contribute to the sex differences in HFD associated renal inflammation/injury in Dahl SS rats.