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Basis of aggravated hepatic lipid metabolism by chronic stress in high-fat diet-fed rat

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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.

Conflict of interest

None of the authors had a conflict of interest.

Author information

Authors and Affiliations

  1. Department of Physiology, China Pharmaceutical University, 639 Long Mian Road, Nanjing, 211198, Jiangsu Province, China

    Ying Han, Min Lin, Keke Guo, Shanshan Wang & Jihua Fu

  2. Laboratory Animal Center, Southeast University, Nanjing, China

    Xiaobin Wang

  3. Undergraduates of China Pharmaceutical University, Nanjing, China

    Mengfei Sun, Jiao Wang, Xiaoyu Han, Ting Fu & Yang Hu

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  1. Ying Han
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  2. Min Lin
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Correspondence to Jihua Fu.

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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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