PUBLICATION
The Hepatotoxicity of Palmitic Acid in Zebrafish Involves the Intestinal Microbiota
- Authors
- Ding, Q., Zhang, Z., Ran, C., He, S., Yang, Y., Du, Z., Zhang, J., Zhou, Z.
- ID
- ZDB-PUB-180710-7
- Date
- 2018
- Source
- The Journal of nutrition 148(8): 1217-1228 (Journal)
- Registered Authors
- Ding, Qianwen, He, Suxu, Ran, Chao, Yang, Yalin, Zhang, Jinxiong, Zhang, Zhen, Zhou, Zhigang
- Keywords
- none
- MeSH Terms
-
- Animal Feed
- Animals
- Caspase 12/metabolism
- Chemical and Drug Induced Liver Injury/metabolism
- Chemical and Drug Induced Liver Injury/microbiology*
- Dietary Fats/toxicity*
- Endoplasmic Reticulum Stress*
- Gastrointestinal Microbiome*
- Liver/drug effects*
- Liver/metabolism
- Palm Oil/chemistry
- Palm Oil/toxicity
- Palmitic Acid/toxicity*
- Zebrafish
- PubMed
- 29982798 Full text @ J. Nutr.
Citation
Ding, Q., Zhang, Z., Ran, C., He, S., Yang, Y., Du, Z., Zhang, J., Zhou, Z. (2018) The Hepatotoxicity of Palmitic Acid in Zebrafish Involves the Intestinal Microbiota. The Journal of nutrition. 148(8):1217-1228.
Abstract
Background Palmitic acid (PA) is the main saturated fatty acid naturally occurring in animal fats and vegetable oils. In recent decades, palm oil, an alternative lipid source containing high amounts of PA, has been widely used to replace fish oil in aquafeed.
Objective We investigated the hepatotoxicity of PA in zebrafish and the underlying mechanism.
Methods One-month-old zebrafish fed a high-fat diet (HFD) containing 16% soybean oil and 3 PA-incorporated HFDs [4%, 8%, and 12% PA (12PA)] for 2 wk (experiment 1) and 4 wk (experiment 2) were used to evaluate PA-induced liver damage and endoplasmic reticulum (ER) stress. Germ-free (GF) zebrafish fed low-fat, high-fat, or 12PA diets for 5 d were used to study the direct effects of PA on liver damage (experiment 3). GF zebrafish colonized with HFD or 12PA microbiota for 48 h were used to elucidate the indirect effects of PA-altered microbiota on liver damage (experiment 4). Last, GF zebrafish colonized with HFD or 12PA microbiota were used to evaluate the effects of different microbiotas on PA absorption (experiment 5).
Results In experiment 1, the proportion of PA in the liver linearly increased as its percentage in dietary lipid increased (r2 = 0.83, P < 0.05). In experiment 2, the expression of glucose-regulated protein 78 (Grp78) and C/EBP-homologous protein (Chop) was higher in the 12PA group than in the HFD group (2.2- and 2.7-fold, respectively; P < 0.05). The activity of caspase-12 was increased by 61.1% in the 12PA group compared with the HFD group (P < 0.05). In experiment 3, caspase-12 activity was higher in the 12PA group than in the HFD group (P < 0.05). In experiment 4, GF zebrafish colonized with PA-altered microbiota had higher caspase-12 activity (P < 0.05) than those colonized by HFD microbiota. In experiment 5, PA-altered microbiota promoted PA absorption (P < 0.05) and aggravated ER stress and liver damage in the context of high-PA feeding.
Conclusions The PA-altered microbiota indirectly induced ER stress and liver damage in zebrafish. Moreover, the PA microbiota promoted the absorption of PA, leading to enhanced PA overflow into the liver and aggravated hepatotoxicity of PA in zebrafish.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping