We thank the reviewers for all their insightful comments, which have helped us greatly improve the manuscript. Our responses to all the reviewers’ comments are detailed below. We have reformatted the manuscript to meet PLOS ONE style requirements.

Comment 1: Following the suggestion raised by the reviewer, it could be also interesting to analyze the relation between digestive enzymes and protein efficiency ratio.

Response: In previous studies, we found that dietary A. senticosus supplementation increased the activity of intestinal digestive enzymes (amylase, trypsin, lipase) of hybrid yellow catfish. The organic substances (protein, fat, carbohydrate) in the diet are digested in the digestive tract, and then hydrolyzed into smaller molecules that are easily absorbed and used in the fish body. The digestive enzymes play important roles in this process. Previous studies have shown that, in fish, the digestion and absorption of dietary protein can be improved by increasing trypsin activity, thereby promoting the synthesis of fish protein and promoting its growth [1, 2].

We have added the protein efficiency ratio data (PER) in Table 3, and discussed the difference of PER at dietary A. senticosus supplementation in the results section (page 8, lines 154-155), and discussed the results in the discussion section (page 17, lines 369-373).

Comment 2: Is this fish a kind of low fat fish which can be expressed by aquaculture activities to be high fat content? Market always prefers original taste.

Response: Yellow catfish is an important freshwater economic fish in China. It has delicious meat and high nutritional value, and is loved by consumers. Because of the high demand for yellow catfish, the natural catch cannot meet the needs of consumers, so farmers are pursuing a higher-yield aquaculture model for profit. (According to statistics from the China Fisheries Yearbook, the total yield of yellow catfish in China in 2018 and 2019 was 509,610 and 536,964 tons, respectively, an increase of 5.37%[3].) Feeding large amounts of formulated feed can easily lead to excessive energy intake and fat deposition, and the excess fat may accumulates on muscle, but mainly in the liver and abdominal cavity. Fat deposition in the liver can increase the pressure on the liver, damage the cell structure, and affect liver metabolism, leading to slow growth and weakened immunity of farmed fish [4-6] and causing huge economic losses.

Siberian ginseng (Acanthopanax senticosus) is rich in nutrients such as trace elements and amino acids, which are required by animals, as well as a variety of other active ingredients [7, 8], and A. senticosus also plays a role in regulating lipid metabolism [9, 10]. Therefore, to tackle some of the various problems caused by intensive aquaculture, we explored the mechanism by which dietary A. senticosus supplementation affects lipid metabolism in the liver of hybrid yellow catfish.

Comment 3: The authors said that they measured glycogen (page 6, line 139), but no data is available in this parameter?

Response: We have shown the glycogen data in Fig 3 and discussed liver glycogen content in the discussion section (page 18, lines 401-403).

Comment 4: The present of some antinutrients in Chinese ginseng could probably affect the results and this can be considered for more discussion.

Response: We have addressed this concern in our detailed response to comment 22 below.

Comment 5: Abstract- Give the duration of the experiment here.

Response: We have included this information in the revised abstract (line 16).

Comment 6: Abstract- Also some numerical data should be given in summary.

Response: We have included some numerical data in the revised abstract (lines 17–21 and 24–27).

Comment 7: Keywords- 4 of 7 exactly repeated in the title and should be moderately changed.

Response: We have changed the keywords to avoid repetition (line 34–35).

Comment 8: Introduction- Just some explanation on the measured parameters in this study could mature the introduction.

Response: We have added explanations about the triglyceride (TG), total cholesterol (TC), triiodothyronine (T3), thyroxine (T4), and catabolic enzymes lipoprotein lipase (LPL) and hepatic lipase (HL) indicators in the introduction section (page 5, lines 88-105). Because we analyzed and screened the enrichment pathways and differentially expressed genes based on the results of transcriptome sequencing, and selected five differentially expressed genes related to lipid metabolism, we discussed these five genes in the discussion section.

Comment 9: Introduction- The culture importance and problems in the examined fish should be given.

Response: We mentioned current aquaculture problems in the introduction section (page 4, lines 46–51) and added relevant information about yellow catfish farming (page 4, lines 69–72).

Comment 10: Page 4, line 90- use the same unit for g/kg throughout the text.

Response: We have used the same unit throughout the revised manuscript (page 6, line 113).

Comment 11: Page 4, line 95-97- the preparation of the diets is not complete in terms of the amount of added water and oil, time for drying and so on.

Response: The content of each component in the feed is given in Table 1. We added relevant content information to the methods section under ‘Experimental diets’ (page 6, lines 118, 120–121).

Comment 12: Page 4, line 108-109- give the other water physio-chemical parameters. The tank dimension, source of water and flow rate is not given!

Response: We have added this information to the revised manuscript (page 7, lines 130, 133–135).

Comment 13: Page 8, line 196- the company info for this version of SPSS in not correct.

Response: We have included this information as “SPSS ver. 22.0 (IBM Corp., Armonk, NY, USA)” (page 10, lines 223–224).

Comment 14: Results- Give the final weight of fish for better comparison by readers.

Response: We have included the initial and final weights in Table 3.

Comment 15: Page 13, line 292- change rate to level.

Response: We changed “rate” to “level” (page 16, line 361).

Comment 16: Page 13, line 296-298- but no changes were observed in FCR.

Response: We found that A. senticosus supplementation significantly enhanced intestinal digestive enzyme activities. Feed conversion rates (FCRs) were not significantly different, but they showed a downward trend with A. senticosus supplementation and the FCR was lowest with 4 g/kg A. senticosus. Jang et al. [11] found that dietary A. senticosus reduced the FCR of broiler chicks. Therefore, we considered that A. senticosus promoted the digestion and absorption of nutrients, but this result was not significant, likely because of differences between fish and chicken.

Comment 17: Page 13, line 299- should be present as strongest effect on…

Response: We changed the wording as suggested (page 17, line 368).

Comment 18: Page 13, line 300-302- not related to the changes of enzymes. Some ingredients and the levels should be an effective reason.

Response: The original statement was incorrect and has been deleted. A. senticosus contains a variety of nutrients and active ingredients, and has been shown to promote the development of animal intestines and promote secretion from digestive glands [12].

Comment 19: Page 13, line 306-308- but the authors did not measure the catabolic enzymes.

Response: To supplement the data about the catabolic enzymes, we measured the activities of lipoprotein lipase (LPL) and hepatic lipase (HL) in the liver homogenate using an ELISA kit according to the manufacturer’s instructions (Table 5). We also added information about LPL and HL in the introduction section (page 5, lines 94–98), included the enzyme activity test in the result section (page 13, lines 271–276), and discussed the results in the discussion section (page 17, lines 386–394).

Comment 20: Page 13, line 309-310- this sentence is repeated in introduction.

Response: We deleted the repeated sentence.

Comment 21: Page 14, line 336- change to HSI.

Response: This was changed (page 18, line 415).

Comment 22: Page 15, line 369-370- I'm not agree with this as those are antinutrients and many studies showed the negative impacts of these on growth and metabolism of animals.

Response: The A. senticosus samples were tested by the ZKGX Research Institute of Chemical Technology (Chemical Lab, Beijing, China) and were found to contain active ingredients such as polysaccharides, flavonoids, and saponins, whereas the content of lignans and other ingredients was low or undetectable. These active ingredients have been found to positively affect animal growth [13], enhance immunity [14], improve antioxidant capacity [15], treat inflammation [16, 17], and regulate lipid metabolism [9, 10].

Sui et al. [18] injected A. senticosus saponins into experimental hyperlipidemia rats and found that after 21 days, serum TG and TC levels decreased significantly and liver fat deposition was significantly reduced. Related studies have shown that plant active polysaccharides have a lipid-lowering function; for example, Astragalus membranaceus polysaccharides [19, 20] and Lycium barbarum polysaccharides [21] all show similar effects. Meng et al. [22] showed that A. senticosus polysaccharides have a positive effect on the inhibition of lipid peroxidation of the erythrocyte membrane. Wen et al. [23] found that the total flavonoids of A. senticosus increased erythrocyte membrane fluidity, reduced blood viscosity, and improved hemorheology factors.

On the basis of these results, we considered that the positive effects of A. senticosus supplementation on lipid-lowering and growth may be related to the polysaccharide, flavonoid, and saponin contents of A. senticosus.

Comment 23: Reference- There are many mistakes in references in terms of format, journal abbreviations, scientific names, etc. such as lines 394-395, 411,414-415,417, 421-422, and so on.

Response: We have reformatted the references to remove errors.

Comment 24: Table 1- give the unit in parenthesis in front of the ginseng. Correct middling with small letter. Put all proximate analyses of the diets in terms of ash, dry matter and other items.

Response: We modified Table 1 to include all the suggested changes.

Comment 25: Table 3- insert the initial and final fish weights.

Response: The initial and final fish weights have been included in Table 3.

Comment 26: Table 4- why no data on T3, T3 and the ratio of T3:T4 are available in this table!? Those should be given here. The unit of TP is generally g/dL.

Response: We have added the T3, T4, and T3/T4 data to Table 4, and plotted their levels in Fig 2. Serum total protein (TP) content was measured using a fully automatic biochemical analyzer (bs-400, MINDRAY, Shenzhen, China) according to the manufacturer’s instructions; the TP unit is given as g/L, so we did not change the unit. Qiang et al. [24, 25] and Bao et al. [26] also reported TP content in g/L.

Comment 27: Figures- The quality of all figures is low in the reviewers' file.

Response: We changed the figure mode to sRGB and increased the resolution to 600 dpi to improve the quality of the figures.

Comment 28: Figure 1: no data are available to how the broken-line was analyzed.

Response: We calculated the specific growth rate (SGR) of the hybrid yellow catfish and included the data in Table 3. We used a two-slope broken-line model to analyze the relationship between SGR and dietary supplementation with A. senticosus according to the method of Qiang et al. [27]. This information has been added to the legend for Fig 2.

Comment 29: Figure 2: change value to ratio.

Response: We changed “value” to “ratio” in Fig 2.

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