Effects of high-fat vs. low-fat diets on mammalian target of rapamycin signaling and metabolic measures in spontaneously hypertensive rats

Preliminary studies in the Division of Nutrition’s Nutrition Sciences lab have shown that spontaneously hypertensive rats (SHRs) fed high-fat diets (HF; 60% kcals) have a reduction in cardiac mammalian target of rapamycin (mTOR) signaling, with no impairments in whole body insulin tolerance. Having previously demonstrated that suppression of mTOR decreased cardiac hypertrophy, it was hypothesized that an HF diet would decrease cardiac hypertrophy, without causing insulin resistance or altering insulin-stimulated mTOR signaling. Forty-eight 5-week-old rats (SHR n = 24; Wistar Kyoto (WKY; normotensive control) n = 24) were randomly assigned to consume an HF or low-fat (LF) diet (10% kcals). After 10 weeks, cardiac hypertrophy was similar in SHRHF vs. SHRLF. Insulin stimulation increased (p < 0.05) phosphorylation of heart and gastrocnemius Akt (Ser473) and S6 (Ser235/236) regardless of genotype or diet with SHRHF responding more robustly (p < 0.05) than WKYHF. Fat pad mass was 37% greater in WKYHF vs. WKYLF, but only 20% greater in SHRHF vs. SHRLF. Similarly, plasma leptin was ~70% greater in WKYHF vs. WKYLF, but unchanged in SHRHF vs. SHRLF. Plasma adiponectin was reduced (p < 0.05) in SHRHF vs. both WKY groups. In conclusion, while an HF diet did not prevent cardiac hypertrophy in SHRs, it also did not cause diet-induced insulin resistance, hyperleptinemia, or weight gain with only a modest increase in adiposity. In contrast to previous thinking, an HF diet may enhance insulin-stimulated mTOR signaling in SHRs.