Abstract

Regular aerobic exercise is effective for weight loss and reducing adiposity, but its effects on hepatic lipid metabolism and composition while consuming a high fat/high calorie diets are not well understood. Here we describe the effects of no exercise (Sed) or progressive treadmill exercise training (Ex) over 8 weeks (5 days/week up to 45 min/day, 25 m/min, 5% grade, on a motorized treadmill) in mice fed either low fat ((LF) 5 mg/g; 3.8 kcal/g) or high fat ((HF) 350 mg/g; 5.2 kcal/g) diet on hepatic markers of cholesterol (Chol) synthesis and absorption, de novo lipogenesis (DNL) and stearoyl‐CoA desaturase (SCD) activity. Hepatic Chol, lathosterol (LS), campesterol (CS), beta‐sitosterol (BS) and fatty acid composition were determined by gas chromatography. Differences were analyzed by 2‐way ANCOVA, with food intake as the covariate. Although total hepatic Chol and LS were not different across groups, both LF groups had higher hepatic CS (p=0.002) and BS (p=0.014) content. Irrespective of exercise, the LS/Chol ratio, an indicator of Chol synthesis, tended to be higher in the LF groups (p=0.051). Both LF groups had higher CS/Chol (p<0.0001) and BS/Chol (p=0.001), indicating higher Chol absorption. While there was no difference due to exercise alone, LF‐Ex mice had the highest Chol absorption (diet x Ex; CS/Chol, p=0.051 and BS/Chol, p=0.016). DNL (16:0/18:2n‐6) and SCD activity (16:1/16:0 and 18:1/18:0) were higher (16:1/16:0) in the LF (p<0.0001), but decreased in the Ex groups (p<0.0001) with the LF‐Ex having the largest decrease (diet x Ex; 16:1/16:0, p=0.016). In conclusion, our data show that 8 weeks of progressive treadmill exercise increases hepatic cholesterol absorption and decreases SCD activity.Grant Funding Source: Supported by King's College London and University at Buffalo

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