Abstract
Lipid metabolism disorders are found ubiquitously in farmed fish and occur as a result of excessive fat accumulation. Previous studies have found that miR-33 is involved in lipid metabolism; however, its role in fish lipid metabolism is unclear. We sought to clarify this relationship in grass carp in vivo and in vitro. Our findings revealed the length of miR-33 to be 65 bp. Phylogenetic tree analysis showed that grass carp miR-33 was most closely related to fish miR-33 (Siganus canaliculatus). Hepatocytes transfected with miR-33 mimic displayed markedly raised TG content (P < 0.05) as well as increased levels of lipid synthesis-related transcription factors (P < 0.05). Compared with blank and saline groups, total serum cholesterol, AST, and LDL levels were suppressed in groups treated with the miR-33 antagomir (P < 0.05). Moreover, the expression levels of PPARγ and SREBP-1c mRNA were significantly decreased in contrast to those found in the control group (P < 0.05). Similar findings were noted in the expression of immune-related proinflammatory molecules (TNFα, IL-1β, IL-6, and NF-κB), which also demonstrated decreased levels (P < 0.05). Conversely, high expressions of anti-inflammatory factors (TGF-β1 and IL-10) were noted (P < 0.05). This investigation strongly supports the role of miR-33 in hepatopancreas-based lipid metabolism and immunity. miR-33 may have been highly conserved in early vertebrates in order to facilitate liver-specific metabolic and immunomodulatory functions. Our findings provide a basis for further investigations exploring the mechanisms surrounding fish lipid metabolism and may aid in preventing and treating immunocompromised fish as well as fish with fatty hepatopancreas, and other metabolic diseases.
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The data that support the findings of this study are available from the corresponding author, upon reasonable request.
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Abbreviations
- TG:
-
Triglyceride
- TP:
-
Total protein
- HDL:
-
High-density lipoprotein
- LDL:
-
Low-density lipoprotein
- Glu:
-
Glucose
- ALT:
-
Alanine aminotransferase
- AST:
-
Aspartate aminotransferase
- CHOL:
-
Cholesterol
- TGF-β1:
-
Transforming growth factor-1
- NF-κB:
-
Nuclear factor-κB
- TNF-α:
-
Tumor necrosis factor-α
- miRNA:
-
MicroRNA
- CPT1:
-
Carnitine palmitoyltransferase 1
- ATGL:
-
Adipose triglyceride lipase
- FAS:
-
Fatty acid synthase
- ACC:
-
Acetyl CoA carboxylase
- SCD-1:
-
Stearoyl-coenzyme A desaturase 1
- PPAR:
-
Peroxisome proliferator-activated receptor
- SREBP-1:
-
Sterol regulatory element-binding proteins-1
- IL-1β:
-
Interleukin-1β
- IL-6:
-
Interleukin-6
- IL-10:
-
Interleukin-10
- AMPK:
-
AMP-activated protein kinase
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Funding
This work was supported by Joint Fund of Natural Science Foundation of China and Henan Province (U1704109), National Natural Science Foundation of China (31402311, 31673671, and 31872581), Science and Technology Breakthrough Major Project in Henan Province (182102410031), and Zhongyuan thousand talents plan-leading talents of Zhongyuan Science and Technology of Henan Province (204200510025).
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Ronghua Lu, Mengjun Lin, and Feng Yang designed the research study and interpreted the data; Ronghua Lu performed the experiments, analyzed the data, and wrote the manuscript; Shenzong Jia collected the literature; Guoxing Nie, Xiaolin Meng, Yuru Zhang, and Chaobin Qin revised the manuscript. All authors have read and approved the final manuscript.
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Lu, RH., Lin, MJ., Yang, F. et al. Anti-miR33 therapy improved hepatopancreatic lipid and immune metabolism disorders in grass carp, Ctenopharyngodon idella. Fish Physiol Biochem 47, 1611–1622 (2021). https://doi.org/10.1007/s10695-021-00956-3
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DOI: https://doi.org/10.1007/s10695-021-00956-3