Abstract
Our previous study has demonstrated that long-term stress, known as chronic stress (CS), can aggravate nonalcoholic fatty liver disease in high-fat diet (HFD)-fed rat. In this study, we tried to figure out which lipid metabolic pathways were impacted by CS in the HFD-fed rat. Male Sprague–Dawley rats (6 weeks of age, n = 8 per group) were fed with either standard diet or HFD with or without CS exposure for 8 weeks. Hepatic lipidosis, biochemical, hormonal, and lipid profile markers in serum and liver, and enzymes involved in de novo lipogenesis (DNL) of fatty acids (FAs) and cholesterol, β-oxidation, FAs uptake, triglycerides synthesis, and very low-density lipoprotein (VLDL) assembly in the liver were detected. CS exposure reduced hepatic lipidosis but further elevated hepatic VLDL content with aggravated dyslipidemia in the HFD-fed rats. There was a synergism between CS and HFD on VLDL production and dyslipidemia. PCR and western blot assays showed that CS exposure significantly promoted hepatic VLDL assembly in rats, especially in the HFD-fed rats, while it had little impact on DNL, β-oxidation, FAs uptake, and triglycerides synthesis in the HFD-fed rats. This phenomenon was in accordance with elevated serum glucocorticoid level. The critical influence of CS exposure on hepatic lipid metabolism in the HFD-fed rats is VLDL assembly which might be regulated by glucocorticoid.
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Abbreviations
- NAFLD:
-
Nonalcoholic fatty liver disease
- IR:
-
Insulin resistance
- CS:
-
Chronic stress
- HFD:
-
High-fat diet
- HPA:
-
Hypothalamic–pituitary–adrenal
- FAs:
-
Fatty acids
- TGs:
-
Triglycerides
- VLDL:
-
Very low-density lipoprotein
- FFAs:
-
Free fatty acids
- CH:
-
Cholesterol
- DNL:
-
De novo lipogenesis
- HI:
-
Hepatic index
- VOI:
-
Visceral obesity index
- TC:
-
Total cholesterol
- ALT:
-
Alanine aminotransferase
- AST:
-
Alanine aminotransferase
- FFA:
-
Free fatty acids
- MDA:
-
Melondialdehyde
- SOD:
-
Superoxide dismutase
- HDL:
-
High density lipoprotein
- LDL:
-
Low-density lipoprotein
- TNF-α:
-
Tumor necrosis factor-α
- HOMA-IR:
-
Homeostasis Model of Assessment–Insulin Resistance
- PCR:
-
Polymerase chain reaction
- RT-PCR:
-
Reverse transcription-PCR
- FATP5:
-
Fatty acid transport protein 5
- HMGCR:
-
β-hydroxy-β-methylglutaryl-coa reductase
- ACCase:
-
Acetyl-CoA carboxylase
- GPAT:
-
Glycerin-3-phosphate acyltransferase
- ACOX-1:
-
Acyl-CoA oxidase-1
- CPT-1:
-
Carnitine palmitoyltransferases-1
- ApoB100:
-
Apolipoprotein B 100
- ACAT2:
-
Acyl coenzyme A-cholesterol acyltransferase-2
- MTTP:
-
Microsomal triglyceride transfer protein
- HE:
-
Hematoxylin-eosin
- SD:
-
Standard deviation
- ANOVA:
-
Analysis of variance
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Acknowledgments
The authors are grateful to Wenxia Bai, an associate researcher (Jiangsu center for safety evaluation of drugs, China) for her contribution in histopathological examination, and professor Rong Hu for her contribution in manuscript revision.
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None of the authors had a conflict of interest.
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Han, Y., Lin, M., Wang, X. et al. Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat. Endocrine 48, 483–492 (2015). https://doi.org/10.1007/s12020-014-0307-x
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DOI: https://doi.org/10.1007/s12020-014-0307-x