Elsevier

Fish & Shellfish Immunology

Volume 109, February 2021, Pages 1-11
Fish & Shellfish Immunology

Full length article
Dietary taurine modulates hepatic oxidative status, ER stress and inflammation in juvenile turbot (Scophthalmus maximus L.) fed high carbohydrate diets

https://doi.org/10.1016/j.fsi.2020.11.029Get rights and content

Highlights

  • High dietary carbohydrate (21%) accounts for oxidative stress, inflammation and endoplasmic reticulum stress in turbot.

  • Taurine improves the anti-oxidative properties regardless of the dietary carbohydrate levels.

  • Taurine alleviates the stress of oxidation, endoplasmic reticulum and inflammation in turbot fed high dietary carbohydrate.

  • The optimal dietary taurine content is 1.40% for turbot based on the growth data.

Abstract

This study was conducted to explore the beneficial role of taurine against chronic high carbohydrate diet-induced oxidative stress, endoplasmic reticulum (ER) stress and inflammation, and to understand the underlying molecular mechanisms in turbot. Two 10-week feeding trials were simultaneously conducted. For the one, six experimental diets with graded levels of taurine supplementation (0, 0.4%, 0.8%, 1.2%, 1.6% and, 2.0%, respectively) and 15% of carbohydrate were used. For the other one, three graded levels of dietary taurine supplementation (0.4%, 1.2% and 2.0%, respectively) with 21% of carbohydrate were used. The results showed that higher expression level of inflammation cytokines and ER stress related genes were detected in higher dietary carbohydrate group. In both feeding trials, 1.2% of dietary taurine supplementation improved anti-oxidative status by decreasing the content of malondialdehyde, increasing the catalase activity and total anti-oxidative capacities. In feeding trial 1, appropriate taurine supplementation lowered contents of tumour necrosis factor-a, interleukin-6, aspartate aminotransferase and alkaline phosphatase in plasma, and decreased the expressions of pro-inflammatory cytokines, such as interleukin-8 (il-8) and interferon‐γ (ifn-γ). Furthermore, dietary taurine reduced ER stress by decreasing the mRNA levels of activating transcription factor 6, protein kinase R-like endoplasmic reticulum kinase and G protein-coupled receptor 78. The optimal dietary taurine content was estimated as 1.40% based on the analysis of specific growth rate. In feeding trial 2, dietary taurine supplementation attenuated liver inflammation partly referring to significantly down-regulated mRNA levels of nuclear transcription factor‐κB p65, ifn-γ, interleukin1β and up-regulate the transcript of ribosomal protein S6 kinase 1. Dietary taurine supplementation in feeding trial 2 significantly increased the Nrf2-related factor 2 protein level and decreased the NFκB p65 protein level only at 21% of dietary carbohydrate level. Taurine can alleviate the oxidative damage and inflammation caused by 21% of dietary carbohydrate to a certain degree. Overall, the present study confirmed that dietary taurine supplementation improved growth performance and anti-oxidative response, and reduced liver inflammatory and ER stress processes induced by high dietary carbohydrate in turbot.

Introduction

Carbohydrates are regarded as the most economical class of energy yielding nutrients for aquatic animals due to its abundance and relatively low cost [1]. It also has a protein-sparing effect, thus reducing protein catabolism for energy and decreasing the ammonia emission into the environment [2]. However, unlike mammals, most fish species have a relatively low capacity to utilize dietary carbohydrates and showed persistent postprandial hyperglycaemia after a glucose load or a carbohydrate-enriched meal [3]. In addition, when administrated with excessive carbohydrate levels, fish especially the carnivorous species showed high mortality, reduced growth performance, low nutrient utilization and poor immunity, etc. [4,5].

In mammals, accumulating evidence indicates that hyperglycemia, inflammation and glucose intolerance are inter-related and are reciprocal causation [6]. Many studies have demonstrated that chronic high carbohydrate intake related to the immune response of animals, such as anti-oxidative capacity and inflammation [7,8]. Acute hyperglycaemia induced by a high carbohydrate diet has been demonstrated to cause inflammation and oxidative stress by generating reactive oxygen species (ROS) [9,10]. Overproduction of ROS causes tissue damage through several major mechanisms, such as increasing intracellular formation of advanced glycation end products (AGEs) and activating the protein kinase C pathway [10,11]. High glucose levels result in increased protein glycation and subsequent formation of advanced glycation end products (AGE), thus accelerating the Maillard reaction [12]. Receptor for AGE (RAGE) binding induces the production of ROS, which in turn activates the pleiotropic transcription factor nuclear factor (NF)- κB, causing multiple pathological changes in gene expression, thus inflammation [13]. Substantial evidences showed that endoplasmic reticulum (ER) stress played a pivotal role in tissue dysfunction and death. Furthermore, persistent hyperglycemia could induce accumulation of unfolded proteins in the ER, a cellular condition termed ER stress, and then activate all three ER stress signaling pathways [14]. At the same time, both ROS generation and ER stress could activate intracellular nuclear factor κB (NF-κB) translocates to the nucleus and promote the transcription of pro-inflammatory cytokines, such as tumour necrosis factor-a (TNF-α) and interleukin-6 (IL-6), and thus inflammation [9,15]. In short, high carbohydrate diet may trigger ER stress and inflammation which in turn results in the damage of liver function.

However, such information in aquatic species is still quite limited. In fish, previous studies demonstrated that excessive carbohydrate intake could increase the oxidative stress, induce chronic inflammation and even produce direct hepatocyte injury, which is associated with the decreased expression of anti-oxidative enzymes and increased expression of related cytokines [[16], [17], [18], [19]]. The gene expressions of cytokines were regulated by intracellular NF-κB and target of rapamycin (TOR) signaling pathway in some fish species, such as grass carp and turbot [[20], [21], [22]]. In addition, excessive carbohydrate intake could activate some major pro-inflammatory transcription factors, such as NF-κBs, leading to the increased transcriptions of the pro-inflammatory genes tnfα, interleukin 1β (il1β) and interleukin 8 (il-8)) and thus inflammation in Japanese flounde, hybrid grouper and Megalobrama amblycephala [16,23,24]. However, the underlying mechanisms that how high carbohydrate diet induced the inflammatory response still remain obscure, as warrants further studies. Moreover, to our knowledge, few studies were conducted to examine whether high carbohydrate diet induced the ER stress in fish species. So, systematic studies to investigate the relationship between high carbohydrate diet and inflammation response and ER stress in fish are quite necessary.

Taurine is the most abundant free amino acid in animal tissues, and is involved in a wide variety of functions in fish physiology, including growth promotion, constituent of bile, and anti-oxidative action [[25], [26], [27]]. In mammals and humans, evidence designates taurine as a potent regulator of the pro-inflammatory and immune response [28,29]. Literature suggests that taurine treatment can mitigate the ROS production [30], alleviate the overexpression of NF-κB, and inhibit the elevation of pro-inflammatory cytokines [31,32]. Taurine performs as a scavenging element against glycation and protects intracellular production of AGEs and carbonyl compounds, thus alleviates the tissue damage induced by hyperglycemia [33]. As a tripeptide, glutathione (GSH) can serve as an endogenous antioxidant that protects cells against ROS. Since cysteine is a precursor of taurine and GSH, taurine supplementation may cause increase in GSH levels by directing cysteine into the GSH synthesis pathway [34]. Previous studies supported that taurine played a protective role in cells via suppressing apoptosis or ER stress [29,35,36].

In fish, although most of the previous studies focused on the growth-promoting effect of taurine, there are some researchs reported on the antioxidant properties [[37], [38], [39]]. Studies demonstrated that taurine supplementation could increase the content of GSH and activity of superoxide dismutase (SOD), and down-regulate malondialdehyde (MDA) content, thus prevent against tissue damage caused by oxidative stress in fish, such as European seabass, yellow catfish, grass carp and pufferfish [26,[40], [41], [42]]. In addition, taurine attenuated apoptosis induced by CdCl2 in primary liver cells isolated from Atlantic salmon [43]. However, only some apparent parameters were considered, such as anti-oxidative enzymes, mortality and activity of the immune related enzymes. The underlying mechanisms on how taurine modulating inflammation and ER stress in fish were generally unknown.

Turbot (Scophthalmus maximus L.) is an economically valuable marine carnivorous fish species. Previous studies indicated that juvenile turbot fed diets with approximate 15% carbohydrate could obtain improved growth performance and feed efficiency. However higher dietary carbohydrate contents (>20%) suppressed the growth [44,45]. In our previous study, 21% of dietary carbohydrate diet significantly increased the plasma glucose level and decreased the feed efficiency of juvenile turbot. Meanwhile, 1.2% dietary taurine supplementation could significantly decreased the plasma glucose and AGEs level, and improve the dietary carbohydrate utilization mainly by increasing the glucose uptake and glycolysis [46]. The present study was conducted to investigate the potential effects of chronic taurine treatment on anti-oxidation, anti-inflammation, anti-ER stress and its possible molecular mechanisms in turbot fed lower (15%) and higher (21%) levels of dietary carbohydrate. This facilitates the discovery of effective approaches to improve the anti-oxidative function in fish as well as open up a new approach to promote its carbohydrate utilization.

Section snippets

Materials and methods

All animal care and handling procedures in this study were approved by the Animal Care Committee of Ocean University of China.

Experiment 1

The results of SGR of juvenile turbot are shown in Table 2. The SGR of fish fed the LT-0.0 diet was significantly lower than that in the LT-0.8, LT-1.2 and LT-1.6 groups (P < 0.05). As shown in Fig. 1, second‐order polynomial regression analysis between SGR and dietary taurine content levels estimated the dietary taurine requirement for juvenile turbot was 1.40%. There was no significant difference in survival rate (SR, 98–100%) among the six groups (P > 0.05).

Experiment 2

As can be seen from Table 2, there

Discussion

In carnivorous fish, the optimal levels of dietary carbohydrate were determined as less than 20% [[49], [50], [51]]. In the present study, 21% of dietary carbohydrate led to a decreased feed efficiency in juvenile turbot. In our previous study, compared with 15% of dietary carbohydrate, 21% of dietary carbohydrate resulted in decreased growth and increased plasma glucose and AGEs level in turbot [46]. This result is consistent with the previous studies in which high carbohydrate diet usually

Conclusion

In summary, the present study indicated that dietary supplementation of taurine could protect the turbot from oxidation, ER stress and inflammation induced by the high dietary carbohydrate level (21%). These protective effects were performed by improving Nrf2-mediated anti-oxidative enzyme activities, down-regulating pro-inflammation and ER stress associated gene expressions, up-regulating the anti-inflammation genes.

CRediT authorship contribution statement

Yue Zhang: Formal analysis, Investigation, Writing - original draft. Zehong Wei: Formal analysis, Investigation. Mengxi Yang: Formal analysis, Investigation. Danni Liu: Formal analysis, Investigation. Mingzhu Pan: Formal analysis, Investigation. Chenglong Wu: Formal analysis, Investigation. Wenbing Zhang: Conceptualization, Methodology, Writing - review & editing, Supervision, Funding acquisition. Kangsen Mai: Conceptualization, Methodology.

Declaration of competing interest

The authors declare that there are no conflicts of interest.

Acknowledgment

This study was financially supported by the National Key R & D Program of China (2018YFD0900400), and the Marine Economic Innovation and Development Regional Model City Project (2016) of Qingdao, China.

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