FXR, a Key Regulator of Lipid Metabolism, Is Inhibited by ER Stress-Mediated Activation of JNK and p38 MAPK in Large Yellow Croakers (Larimichthys crocea) Fed High Fat Diets

High-fat diets induced abnormal lipid accumulation in the liver of cultured fish that caused body damage and diseases. The purpose of this research was to investigate the role and mechanism of farnesoid X receptor (FXR) in regulating lipid metabolism and to determine how high-fat diets affect FXR expression in large yellow croakers. The results showed that ligand-meditated FXR-activation could prevent abnormal lipid accumulation in the liver and hepatocytes of large yellow croakers. FXR activation increased the expression of lipid catabolism-related genes while decreasing the expression of lipogenesis-related genes. Further investigation found that the promoter activity of proliferator-activated receptor α (PPARα) could be increased by croaker FXR. Through the influence of SHP on LXR, FXR indirectly decreased the promoter activity of sterol regulatory element binding protein 1 (SREBP1) in large yellow croakers. Furthermore, the findings revealed that endoplasmic reticulum (ER)-stress-induced-activation of JNK and P38 MAPK participated in the reduction of FXR induced by high-fat diets. Then, hepatocyte nuclear factor 1α (HNF1α) was confirmed to be an FXR regulator in large yellow croaker, and it was reduced by high-fat diets and ER stress. In addition, co-expression of c-Jun with HNF1α inhibited the effect of HNF1α on FXR promoter, and suppression of P38 MAPK could relieve the HNF1α expression reduction caused by ER stress activation. In summary, the present study showed that FXR mediated lipid metabolism can prevent abnormal lipid accumulation through regulating PPARα and SREBP1 in large yellow croakers, while high-fat diets can suppress FXR expression by ER stress mediated-activation of JNK and P38 MAPK pathways. This research could benefit the study of FXR functions in vertebrate evolution and the development of therapy or preventative methods for nutrition-related disorders.

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Age-dependent effect of high-fructose and high-fat diets on lipid metabolism and lipid accumulation in liver and kidney of rats

Lipids in Health and Disease ◽

10.1186/1476-511x-12-136 ◽

2013 ◽

Vol 12 (1) ◽

pp. 136 ◽

Cited By ~ 46

Author(s):

Uberdan Guilherme Mendes de Castro ◽

Robson Augusto Souza dos Santos ◽

Marcelo Silva ◽

Wanderson de Lima ◽

Maria Campagnole-Santos ◽

...

Keyword(s):

Lipid Metabolism ◽

Lipid Accumulation ◽

High Fat ◽

Dependent Effect ◽

High Fructose ◽

High Fat Diets ◽

Age Dependent ◽

Liver And Kidney ◽

Fat Diets

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Development of leptin resistance in rat soleus muscle in response to high-fat diets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.6.e1374 ◽

2000 ◽

Vol 279 (6) ◽

pp. E1374-E1382 ◽

Cited By ~ 81

Author(s):

Greg R. Steinberg ◽

David J. Dyck

Keyword(s):

Skeletal Muscle ◽

Lipid Metabolism ◽

Soleus Muscle ◽

Leptin Resistance ◽

Safflower Oil ◽

High Fat ◽

Muscle Lipid ◽

High Fat Diets ◽

Rat Soleus Muscle ◽

Fat Diets

Direct evidence for leptin resistance in peripheral tissues such as skeletal muscle does not exist. Therefore, we investigated the effects of different high-fat diets on lipid metabolism in isolated rat soleus muscle and specifically explored whether leptin's stimulatory effects on muscle lipid metabolism would be reduced after exposure to high-fat diets. Control (Cont, 12% kcal fat) and high-fat [60% kcal safflower oil (n-6) (HF-Saff); 48% kcal safflower oil plus 12% fish oil (n-3)] diets were fed to rats for 4 wk. After the dietary treatments, muscle lipid turnover and oxidation in the presence and absence of leptin was measured using pulse-chase procedures in incubated resting soleus muscle. In the absence of leptin, phospholipid, diacylglycerol, and triacylglycerol (TG) turnover were unaffected by the high-fat diets, but exogenous palmitate oxidation was significantly increased in the HF-Saff group. In Cont rats, leptin increased exogenous palmitate oxidation (21.4 ± 5.7 vs. 11.9 ± 1.61 nmol/g, P = 0.019) and TG breakdown (39.8 ± 5.6 vs. 27.0 ± 5.2 nmol/g, P = 0.043) and decreased TG esterification (132.5 ± 14.6 vs. 177.7 ± 29.6 nmol/g, P = 0.043). However, in both high-fat groups, the stimulatory effect of leptin on muscle lipid oxidation and hydrolysis was eliminated. Partial substitution of fish oil resulted only in the restoration of leptin's inhibition of TG esterification. Thus we hypothesize that, during the development of obesity, skeletal muscle becomes resistant to the effects of leptin, resulting in the accumulation of intramuscular TG. This may be an important initiating step in the development of insulin resistance common in obesity.

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