Introduction: Women are more likely than men to be obese, experience higher mortality due to elevated body mass index and are more susceptible to obesity-related Cardiovascular-Kidney-Metabolic Syndrome (CKMS) than men. Our previous studies have shown that high-fat (HF) loading leads to greater increases in blood pressure (BP) on a HF-high-salt (HS) diet in female Dahl rats compared to males. Hypothesis: Increased BP susceptibility to a Western diet in females is associated with altered lipid metabolism and renal mitochondrial dysfunction. Methods: 10-week-old Dahl rats were randomized to a 1) control normal-fat-normal-salt diet (NF-NS, 7.2% calories from lard, 0.4% NaCl, Bio-Serv), or 2) HF diet for 2 weeks (60% kcal lard), followed by HF-HS diet (60% kcal lard, 4% NaCl) for 4 weeks. Gonadal and perirenal adipose tissues were collected to measure triglycerides (TG) via triple quadrupole mass spectrometer. Serum free fatty acid (FFA) composition was measured using gas chromatography mass spectrometry. Renal mitochondria were isolated and loaded with fluorescent dyes to measure H 2 O 2 production (20μM Amplex Red dye) and membrane potential (300nM TMRM dye). Results: 38 TG species with 48–60 acyl carbon chains were identified and grouped by their carbon number for analysis and 7 FFA species identified. In the isolated adipose tissues, females on HF-HS had more long-chain TGs compared to NF-NS fed rats, specifically in the 52 and 54 acyl groups (n=3, p<0.05). There were no alterations in TGs with diet in males. Of the 7 FFAs, both sexes had fewer FFA 16:1 on HF-HS compared to NF-NS (n=3, p=0.003), and the effect was greater in males (n=3, p=0.011). Both sexes showed also had more FFA 18:2 on HF-HS vs. NF-NS (n=3, p=0.037). Spectrofluorimetry revealed mitochondrial H 2 O 2 production was higher in HF-HS fed females vs. males, independent of renal region (cortex: 19152±1158 vs 13441±676, medulla: 10596±876 vs 5446±285; p<0.001). ROS production was independent of membrane potential as measured with TMRM. In both cortex and medulla, mitochondria membrane potential was less in females vs. males (cortex: 183±12 vs 192±12, medulla: 238±8 vs 263±9; p<0.05). Conclusions: Females exhibit a unique lipid profile and greater mitochondrial H 2 O 2 production following a HF-HS diet relative to males. Further studies are needed to elucidate the implications of HF-HS diet-induced alterations in lipid metabolism, mitochondrial dynamics and OXPHOS function for CKMS development in females.
Godley-Boswell et al. (Mon,) studied this question.