Taurine, or 2-aminoethanesulfonic acid, is the major component of bile and is present in many types of animal tissues, including in the gall bladder, blood vessels, eyes, and lower intestine. Although taurine is less known as an amino acid, it is commonly used as a functional component of various types of health drinks. It plays a vital role in adjusting physiological pathways in antioxidation and detoxification. Recent studies indicated that taurine deficiency is associated with persistent obesity, which can be prevented by dietary taurine supplementation [¹,²]. This study tested taurine’s anti-obesity potential with C. elegans, which are frequently used as a tractable system in current biomedical researches [³,⁴].

C. elegans is a very useful animal system in unearthing crucial biological mechanisms that are readily applicable to many higher-level organisms, including humans [⁵,⁶]. Indeed, many recently discovered biological pathways of C. elegans have been proven analogous to those of mammals, despite its relatively simple body structure [^7-9]. Its short generation period of three days enables researchers to perform a drug screen with a time advantage over other test systems, including rodents. Unlike mammals, though, C. elegans lacks leptin-like molecules and their receptor, which participate in regulating fat storage. This makes C. elegans attractive to many researchers who are mass-screening taurine’s potential as an anti-obesity agent, since C. elegans should provide genuine biochemical information on fat storage and utilization that is independent of the hormonal inhibition of food intake. Under certain circumstances, C. elegans serves as a tractable system of studying taurine’s effect on obesity and fat accumulation, and thus, its anti-obesity potential.

Lipid accumulation involves complex processes of lipid biosynthesis, transport, and storage [^10-13]. Lipid biosynthesis is mainly controlled by sterol regulatory element-binding proteins (SREBPs). In mammals, stored fat is consumed according to various transcriptional, translational, and post-translational regulation processes, as in mammals. The SREBP cleavage-activating proteins (SCAPs) are believed to play an important role in activating SREBPs before the SREBPs’ transport into the nucleus. The majority of mammalian lipases are homologous to those in C. elegans. In C. elegans, SBP-1, an SREBP homologue, regulates fatty acid homeostasis by modulating the expression of various lipogenic enzymes.

In C. elegans, the gene products of tub-1 are believed to manage lipid accumulation in cooperation with those of kat-1, which govern fatty acid beta-oxidation [^14-17]. The tub-1 mutants show an excessive obese phenotype especially under an impaired kat-1 gene. The level of fatty acyl-CoA is very important in controlling the rate of beta-oxidation. Its level is rigorously controlled by carnitine acyltranferase, which transports acyl-CoA and its derivatives into the mitochondrion [^18-20]. The enzymatic activity is governed by malonyl-CoA. With increased levels of acetyl-CoA and citrate, however, beta-oxidation decreases in a negative feedback.

This study characterized taurine as an anti-obesity agent in C. elegans that were fed a high-fat diet. The strains of N2, both the normal and RB1600, that mutated in the tub-1 gene were tested under four classes of experiments. The worms were analyzed using Sudan black B staining, food intake assay, triglyceride measurement, and mobility assessment.

Several experiments were performed to examine the effect of taurine on fat accumulation in the normal and tubby strains of C. elegans. Throughout the various taurine treatments, differences in the lipid accumulation were evident both qualitatively and quantitatively under Sudan black staining, food consumption assay, fatty acid quantification, and mobility comparison analysis.

Using C. elegans systems, this study tested taurine’s potential as an anti-obesity agent by helping reduce lipid accumulation in cells. Taurine significantly decreased fat storage depending on its concentration. Without negatively affecting food intake, taurine showed substantially reduced fat accumulation and increased activity, which matched the reduction of lipid storage under its treatment.

Complex cellular mechanisms coordinate the equilibrium between lipid utilization and accumulation [^21-23]. Being critical for the utilization of stored lipids, beta-oxidation converts fatty acids to acetyl co-A and requires the release of fatty acids from triacylglycerides by lipases [^24-27]. The increased activity of the worms after the taurine treatment strongly suggests that the lesser accumulation of fat was due to the higher level of beta-oxidation from the taurine-enhanced activities of the C. elegans.

One of the findings in this study is that taurine had only a minor anti-obesity effect on the tub-1 mutant, unlike on the normal strain. Unlike the wild type, the tubby mutants are known to store more fat due to their inability to control excessive transport to fat storage tissues or to react properly to metabolic signals from ciliated neurons [²⁸,²⁹]. Thus, taurine’s potential anti-obesity effect is not applicable to the lipid accumulation stage or is independent of the pathways where tub-1 is involved.

The Sudan black B staining and triglyceride assays showed inconsistent results concerning the tub-1 mutants in response to taurine. That is, the Sudan black B staining did not show noticeable sensitivity to taurine application, but the triglyceride content measurements showed a significant difference between the taurine-free and the taurine-treated worms. These inconsistent results strongly indicate that the taurine had a more immediate impact on lipid deposition than on fat synthesis.

As in mammals, C. elegans accumulates fat both from its diet and via de novo biosynthesis, and stores lipids in subcellular compartments. Not enough information is available, however, on how C. elegans acquires, synthesizes, uses, and stores lipids, but the consistent results of this study indicate that taurine diminishes lipid storage by enhancing physical activities, rather than by reducing food uptake. Despite these data, the mechanism behind the subcellular targeting and sequestration that dictate the magnitude and numbers of these deposits remains to be determined.

In summary, this study showed that taurine affects lipid deposition in a dose-dependent manner. Reduced lipid storage was evident in the wild-type worms but not in the tub-1 mutants. Unlike tub-1, N2 positively responded to taurine according to its triglyceride content assay. The increased mobility with the taurine treatment may contribute to reduced lipid deposition via enhanced lipid consumption. An additional study is necessary to clarify the potential mechanisms for the fat storage reduction. A new study may be rewarding in finding a definite agent that would modulate tub-1/kat-1 and sbp-1 molecules. Collective treatment of these molecules with taurine is a good way to generally cope with obesity.

SREBP: sterol regulatory element-binding protein; TAB: triglyceride assay buffer; kat-1: 3-ketoacyl-CoA thiolase-1; NGM: nematode growth media

The authors declare that they have no competing interests.

HMK maintained C. elegans and carried out the various taurine treatments and data collection. CHD participated in the design of the study and performed the statistical analysis. DHL participated in obtaining worm strains and coordination and helped to draft the manuscript. All authors read and approved the final manuscript.

This article has been published as part of Journal of Biomedical Science Volume 17 Supplement 1, 2010: Proceedings of the 17th International Meeting of Taurine. The full contents of the supplement are available online at http://www.jbiomedsci.com/supplements/17/S1.

We appreciate Dong-A Pharmaceutical Company for providing materials including taurine. We also thank the Molecular Biology Lab students for confirming the data by repeating the experiments in this study.