Effect of Alpha-Lipoic Acid as a Metabolic and Antioxidant Modulator in Organisms of Interest for Aquaculture
Author: Juan Rafael Buitrago Ramírez (Currículo Lattes)
Adviser: Dr. Jose Maria Monsserat
Abstract
One of the research areas that has recently garnered significant attention is the use of bioactive substances in aquaculture nutrition. Alpha-lipoic acid (LA) has been suggested as a potential candidate to modulate desirable metabolic and antioxidant responses for animal production. Although the exact mechanisms by which LA affects animal metabolism are not fully understood, substantial evidence suggests that this supplement promotes catabolic metabolism and antioxidant status through the activation of pathways involved in mitochondrial biogenesis, β-oxidation, and the assimilation of circulating glucose via redox regulation of the insulin–insulin receptor interaction and the production of antioxidant defenses. However, for the application of LA in aquaculture, it is necessary to evaluate the effects of this compound considering the specific production characteristics and species diversity cultivated in this activity. Therefore, the objective of this thesis is to provide bibliographic, biochemical, physiological, zootechnical, and statistical data regarding the importance of biological knowledge of species for optimizing their productive metabolism. The thesis primarily assessed the effects of LA in animal models relevant to aquaculture. Initially, within a general overview (Chapter 1), it was theorized how nutritional compounds can interact through various biochemical approaches to promote physiological processes that affect phenotypic traits favorable to production. Subsequently, different concentrations of LA (0.05, 0.1, 0.5, 1, 5, 10 µM) were tested on Artemia sp. nauplii. The effects of LA on protein, triglyceride, glucose, and lactate levels in the nauplii were evaluated. Similarly, the concentration of total ammonia nitrogen (TAN) in the water was measured. To assess changes induced by LA on antioxidant defenses in parallel with energy metabolism, the activity of the electron transport system (ETS) and the production of reactive oxygen species (ROS) were evaluated. The experimental period was set at 24 hours post-hatching, with samples of animals and water collected every 6 hours to evaluate time-dependent effects of LA on the aforementioned variables. Among the results, a reduction in TAN production was observed as an effect of LA; moreover, LA was able to influence protein, glucose, and lactate levels. The results showed increases in ETS activity both in vivo and in vitro, as well as a decrease in ROS production (Chapter 2). Observing the increase in ETS activity induced by LA, an increase in dietary caloric content was evaluated as a mechanism to compensate for the extra energy expenditure induced by LA. Thus, in Chapter 3, sodium acetate (SA) was evaluated as an additional energy source and metabolic modulator. Newly hatched Artemia were supplemented with combinations of different concentrations of LA (0, 0.05, 0.5, and 5 µM) and SA (0, 2, 4, and 8 mM). Every 6 hours over 24 hours, Artemia samples were collected to assess protein, triglyceride, and glucose content, while water samples were collected to evaluate TAN production at each time point. Supplementation caused a decrease in the energy content of animals receiving LA, whereas higher energy levels were observed in animals treated with SA. Notably, animals co-administered with 0.05 µM LA and 8 mM SA exhibited the highest energy content. This points to effective energy conservation with SA supplementation and the potential for integrated use of LA and SA (Chapter 3). Finally, available scientific data were gathered to determine, through a meta-analysis, the zootechnical, biochemical, and physiological effects of LA supplementation. A systematic search of peer-reviewed scientific literature was conducted in the Scopus database. Articles were selected that met criteria of being original publications where LA was tested as the sole supplement in aquatic organisms. From this selection, results of evaluated parameters in each study were extracted. Meta-analyses revealed high levels of heterogeneity (I²), which could not be explained by established covariates. Consequently, data were quantitatively evaluated using generalized linear models, where effects of LA on zootechnical performance were identified. Energy production metabolic pathways appeared to be activated via mediation of the AMPK protein, which in turn seems to promote increased activity of proteins linked to β-oxidation (Chapter 4).