THE ROLE OF SALVIA HISPANICA L AS IMMUNONUTRITONAL MODULATOR OF HEPATIC LIPID HOMEOSTASIS

Background and objectives: Chia (Salvia hispanica L.) has been regarded as an important source of nutrients as well as several different bioactive compounds. This study aims to evaluate the potential of Salvia hispanica L (Chia) to selectively modulate innate immune TLR4-mediated signaling restraining the growth of hepatoblastoma cells and metabolic programming of macrophages. Methods: A preclinical diet-induced innate immune toll-like receptor (TLR)-4 conditioned model was used to identify innate immune potential of Chia. Mechanistic studies were further performed using hepatoblastoma (HepG2, HB-8965®) cells and the humanized macrophage-like HB-8902® cell line to prove the TLR4 activation potential of the salt-soluble fraction (SSFch) from Chia seeds (defatted). Results: Feeding an innovative Chia-containing bread formulation to a preclinical model with dietary iron-conditioned TLR4 signaling was shown effective to upregulate the hepatic expression of peroxisome proliferator-activated receptor-gamma (PPARγ), which has been shown to suppress inflammation and limit tumor progression in vivo. This observation was accompanied of a restrained production of hepatic hepcidin associated to TLR4 activation. HepG2 cells revealed that upregulation of TLR4 expression (mRNA) was not reflected on IL-6 production that can explain the in vivo hamp levels. Thus, salt-soluble proteins from chia prevent the impairment of hepatic fatty acid oxidation. Measurements of the oxygen consumption rate by HB-8902 cells in presence of SSFch clearly showed increased oxygen consumption by non-mitochondrial enzymes. Lipid mediator profiles (epoxyoctadecenoic acids known as leukotoxins) change with macrophage phenotype. Conclusions: It is concluded that Chia, as ingredient in bread-making, and particularly SSFch promoted beneficial innate immune TLR4-mediated metabolic changes for the regulation of lipid mediators under inflammatory circumstances.