## 4 Discussion
The role of the acyl transferase dgat-2 and acs-22 in _C. elegans_ is crucial for the loading stages of FAs onto the endoplasmic reticulum and both have been associated with a higher accumulation of TAGs [78]. Nevertheless, acs-22 is also involved in the modulation of intestinal permeability as described in other works [79], which could explain the fact that its upregulation is not associated with a higher lipid accumulation in the worms but is related to a better functioning of the intestine absorption. Thus, the reduction in fat content caused by _L. plantarum_ CNTA 628 could also be explained by the direct regulation of the de novo synthesis of the FA pathway in which fat-6, elo-2 and dgat-2 are involved. This effect appears to be more noticeable under high-glucose conditions due to the effect of the triacylglycerol-crych synthesis pathway in which dgat-2 plays a crucial role in the final steps. Interestingly, _mdt-15_ (the ortholog of human MED15) was upregulated in both NGM and NGMg conditions. The role of mdt-15, a co-activator of the nuclear hormone receptor nhr-49, has been previously associated with an increased lifespan in this animal model [80]. Besides being associated with lifespan, the complex mdt-15/nhr-49 also appears to be part of the regulatory system that ensures homeostasis regarding energy metabolism or the oxidative stress response [81]. Besides the mentioned implications, the mdt-15/nhr-49 system is parallel to the Peroxisome Proliferator-Activated Receptor (PPAR) family proteins in mammals, which are key regulators of fat, cholesterol, and glucose homeostasis [82]. The expression of _nhr-49_ has been associated with the fasting response in the worms [83] and with the positive regulation of some of the \(\beta\)-oxidation pathway genes through regulating the expression of acyl-CoA synthetase acs-2 [83]. Therefore, the overexpression of _mdt-15_ caused by _L. plantarum_ CNTA 628 in _C. elegans_ metabolism led to a more in-depth analysis of the expression levels of genes involved in the catabolic \(\beta\)-oxidation pathway. In these subsequent analyses, we observed that both peroxisomal and mitochondrial \(\beta\)-oxidation-related genes were upregulated in worms treated with _L. plantarum_ CNTA 628, in comparison with the corresponding controls. Interestingly, the expression of the nhr-49-regulated gene acyl-CoA synthetase catalyzing _acs-2_, which catalyzes the conversion of a fatty acid to acyl-CoA for further degradation, was upregulated both under normal and high-glucose conditions. This overexpression was also accompanied by the upregulation of the mitochondrial Carnitine Palmitoyl Transferase _cpt-1_ and the peroxisomal B-oxidation genes _acox-1_, _daf-22_ and _maoc-1_, in the glucose-loaded conditions. This gene expression profile is similar to other lactic bacteria described in previous studies. For example, [PERSON] et al. [71] described how _Lactobacillus_ pentosus MJM60383 is able to upregulate the expression of both _nhr-49_ and _acs-2_, therefore modulating the FA degradation pathways and justifying the observed reduction in the lipid content in the worms. Likewise, _L. sakei_ CNTA 173 supplementation effectively diminished fat storage by modulating the expression of _acox-1_ and _maoc-1_, both genes involved in fatty acid beta-oxidation [27]. Finally, it is worth noting that, despite the promising physiological effects observed with this probiotic, the primary limitation of our study lies in the simplicity of the _C. elegans_ model. Its distinct physiology, immune system, and microbiota differ significantly to those of mammals, which may limit the translational relevance of the results. Additionally, the probiotic dosage and administration route in this model often do not reflect physiologically meaningful exposures in humans or other animals. Although _C. elegans_ is a powerful tool for uncovering strain-specific molecular mechanisms, its short lifespan and biological simplicity constrain its ability to model the complex interactions seen in higher organisms.