An atherogenic diet decreases liver FXR gene expression and causes severe hepatic steatosis and hepatic cholesterol accumulation: effect of endurance training.
| Intervention | Direction | Endpoint | Population | Dosage | Impact | Claim # |
|---|---|---|---|---|---|---|
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | increase | liver TAG | Sprague-Dawley rats | 4× | resulted in a large accumulation | #1 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | increase | liver cholesterol | Sprague-Dawley rats | - | elevated | #2 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | increase | plasma cholesterol | Sprague-Dawley rats | - | elevated | #3 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | no change | peripheral fat mass | Sprague-Dawley rats | - | without any gain | #4 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | decrease | FXR transcripts | Sprague-Dawley rats | 60% | associated with an important reduction | #5 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | no change | LXR transcripts | Sprague-Dawley rats | - | no change | #6 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | increase | SREBP-1c mRNAs | Sprague-Dawley rats | - | found an increase | #7 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | decrease | MTP mRNAs | Sprague-Dawley rats | - | found a decrease | #8 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | decrease | HMG-CoA-r transcripts | Sprague-Dawley rats | - | associated with lower | #9 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | decrease | squalene synthase transcripts | Sprague-Dawley rats | - | associated with lower | #10 |
atherogenic diet (AD; 40% lipid, 1.25% cholesterol, kcal) | decrease | ABCG8 transcripts | Sprague-Dawley rats | - | associated with lower | #11 |
exercise training | increase | NPC1L1 | SD-fed animals | - | resulted in higher | #12 |
exercise training | increase | ABCG5 | SD-fed animals | - | resulted in higher | #13 |
exercise training | increase | ABCG8 | SD-fed animals | - | resulted in higher | #14 |
exercise training | no change | NPC1L1, ABCG5, and ABCG8 | AD-fed animals | - | all these increases were suppressed | #15 |
PURPOSE: The aim of this study was to determine the effects of an atherogenic diet (AD; 40 % lipid, 1.25 % cholesterol, kcal) on triglyceride (TAG) and cholesterol accumulation in liver and on gene expression of liver X receptor (LXR) and farnesoid X receptor (FXR) and their target genes and to observe if these responses are affected by endurance training. METHODS: Sprague-Dawley rats (n = 32) were divided into two groups and randomly assigned to an AD or a standard diet (SD) for 7 weeks. Half of the rats in each group were assigned to an exercise training program for 5 days/week. RESULTS: The AD resulted in a large (P < 0.01) accumulation in liver TAG (4×) along with elevated liver and plasma cholesterol without any gain in peripheral fat mass. The liver TAG and cholesterol accumulations were associated with an important reduction (P < 0.01; 60 %) in FXR, but no change in LXR transcripts. Accompanying the reduction in FXR gene expression, we found an increase (P < 0.001) in SREBP-1c and a decrease (P < 0.01) in MTP mRNAs suggesting an increased lipogenesis and a reduced VLDL production, respectively. The AD was also associated with lower HMG-CoA-r, squalene synthase, and ABCG8 transcripts (P < 0.001). In the intestine, exercise training resulted in higher NPC1L1, ABCG5, and ABCG8 in SD-fed animals, while all these increases were suppressed under the AD feeding. CONCLUSIONS: It is concluded that dietary cholesterol favors liver TAG and cholesterol accumulations associated with an important reduction in FXR transcripts.