Abstract
We investigated the presence of inflammatory signs in the progression of fatty liver disease induced by fasting. Sixty standard black American mink (Neovison vison) were fasted for 0, 1, 3, 5, or 7 days and one group for 7 days followed by re-feeding for 28 days. Liver sections were evaluated histologically and liver mRNA levels indicating endoplasmic reticulum (ER) stress, adipogenic transformation, and inflammation were assessed by quantitative real-time PCR. After 3 days of fasting, the mink had developed moderate liver steatosis. Increased hyaluronan reactivity in lymphocytic foci but no Mallory–Denk bodies were seen in livers of the mink fasted for 5–7 days. Up-regulation of glucose-regulated protein, 78 kDa was observed on day 7 indicating ER stress, especially in the females. Liver lipoprotein lipase and monocyte chemoattractant protein 1 mRNA levels increased in response to 5–7 days of food deprivation, while tumor necrosis factor α (TNF-α) was the highest in the mink fasted for 5 days. The expression of the genes of interest, except for TNF-α, correlated with each other and with the liver fat content. The mRNA levels were found to change more rapidly below n-3/n-6 polyunsaturated fatty acid ratio threshold of 0.15. Following re-feeding, hepatocyte morphology and mRNA abundance returned to pre-fasting levels. Within the studied timeframe, evidence for ER stress, adipogenic transformation, and liver inflammation suggested incipient transition from steatosis to steatohepatitis with potential for development of more severe liver disease. This may present a possibility to influence disease progression before histologically observable steatohepatitis.
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Abbreviations
- ER:
-
Endoplasmic reticulum
- GAPDH:
-
Glyceraldehyde-3-phosphate dehydrogenase
- GRP78:
-
Glucose-regulated protein, 78 kDa
- HA:
-
Hyaluronan
- LPL:
-
Lipoprotein lipase
- MCP-1:
-
Monocyte chemoattractant protein 1
- MDB:
-
Mallory–Denk body
- MUFA:
-
Monounsaturated fatty acid
- NAFLD:
-
Non-alcoholic fatty liver disease
- NAI:
-
Non-alcoholic steatohepatitis activity index
- NASH:
-
Non-alcoholic steatohepatitis
- NEFA:
-
Non-esterified fatty acid
- PUFA:
-
Polyunsaturated fatty acid
- qPCR:
-
Quantitative real-time polymerase chain reaction
- TAG:
-
Triacylglycerols
- TNF-α:
-
Tumor necrosis factor α
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Acknowledgments
We thank the staff of the Canadian Centre for Fur Animal Research for their skillful technical assistance during the mink experiment. This study was supported by the Natural Sciences and Engineering Research Council of Canada (Discovery Grant to K. Rouvinen-Watt, Undergraduate Student Research Award to C. Pal and D. Kryzskaya), the Nova Scotia Department of Agriculture Technology Development Program (DEV26-001), the Canada Mink Breeders’ Association, and the Graduate Research Training Initiative (C. Pal). The authors declare no conflict of interest.
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Communicated by H.V. Carey.
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Rouvinen-Watt, K., Pal, C., Martin, T. et al. Evidence of endoplasmic reticulum stress and liver inflammation in the American mink Neovison vison with benign hepatic steatosis. J Comp Physiol B 184, 913–927 (2014). https://doi.org/10.1007/s00360-014-0845-9
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DOI: https://doi.org/10.1007/s00360-014-0845-9