Dietary Supplementation of Lauric Acid Alleviates the Irregular Estrous Cycle and the Impaired Metabolism and Thermogenesis in Female Mice Fed with High-Fat Diet (HFD).

Lauric acid (LA) has been implicated in the prevention/treatment of obesity. However, the role of LA in modulating an obesity-related female reproductive disorder remains largely unknown. Here, female mice were fed a control diet, high-fat diet (HFD), or HFD supplemented with 1% LA. The results demonstrated that the HFD-induced estrous cycle irregularity and the reduction of serum follicle-stimulating hormone (FSH) were alleviated by LA supplementation. In possible mechanisms, LA supplementation led to significant increase in serum lipid metabolites such as sphingomyelin and lysophosphatidylcholine containing LA (C12:0) and the improvement of glucose metabolism in mice fed HFD. Moreover, impaired body energy metabolism and weakened brown adipose tissue (BAT) thermogenesis of HFD-fed mice were improved by LA supplementation. Together, these findings showed that LA supplementation alleviated HFD-induced estrous cycle irregularity, possibly associated with altered serum lipid metabolites, improved glucose metabolism, body energy metabolism, and BAT thermogenesis. These findings suggested the potential application of LA in alleviating obesity and its related reproductive disorders.

Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR-PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria.

Bile acids (BAs) have been implicated in regulation of intestinal epithelial signaling and function. This study aimed to investigate the effects of hyodeoxycholic acid (HDCA) on intestinal epithelial cell proliferation and explore the underlying mechanisms. IPEC-J2 cells and weaned piglets were treated with HDCA and the contributions of cellular signaling pathways, BAs metabolism profiles and gut bacteria were assessed. In vitro, HDCA suppressed IPEC-J2 proliferation via the BAs receptor FXR but not TGR5. In addition, HDCA inhibited the PI3K/AKT pathway, while knockdown of FXR or constitutive activation of AKT eliminated the inhibitory effects of HDCA, suggesting that FXR-dependent inhibition of PI3K/AKT pathway was involved in HDCA-suppressed IPEC-J2 proliferation. In vivo, dietary HDCA inhibited intestinal expression of proliferative markers and PI3K/AKT pathway in weaned piglets. Meanwhile, HDCA altered the BAs metabolism profiles, with decrease in primary BA and increase in total and secondary BAs in feces, and reduction of conjugated BAs in serum. Furthermore, HDCA increased abundance of the gut bacteria associated with BAs metabolism, and thereby induced BAs profiles alternation, which might indirectly contribute to HDCA-suppressed cell proliferation. Together, HDCA suppressed intestinal epithelial cell proliferation through FXR-PI3K/AKT signaling pathway, accompanied by alteration of BAs metabolism profiles induced by gut bacteria.

cis 9, trans 11, but not trans 10, cis 12 CLA isomer, impairs intestinal epithelial barrier function in IPEC-J2 cells and mice through activation of GPR120-[Ca2+]i and the MLCK signaling pathway.

This study aimed to investigate the effects of conjugated linoleic acid (CLA) on intestinal epithelial barrier function and explore the underlying mechanisms. IPEC-J2 cells and mice were treated with different CLA isomers. The intestinal epithelial barrier function determined by transepithelial electrical resistance (TEER), the expression of tight junction proteins, and the involvement of G-protein coupled receptor 120 (GPR120), intracellular calcium ([Ca2+]i) and myosin light chain kinase (MLCK) were assessed. In vitro, c9, t11-CLA, but not t10, c12-CLA isomer, impaired epithelial barrier function in IPEC-J2 by downregulating the expression of tight junction proteins. Meanwhile, c9, t11-CLA isomer enhanced GPR120 expression, while knockdown of GPR120 eliminated the impaired epithelial barrier function induced by c9, t11-CLA isomer. In addition, c9, t11-CLA isomer increased [Ca2+]i and activated the MLCK signaling pathway in a GPR120-dependent manner. However, chelation of [Ca2+]i reversed c9, t11-CLA isomer-induced MLCK activation and the epithelial barrier function impairment of IPEC-J2. Furthermore, inhibition of MLCK totally abolished the impairment of epithelial barrier function induced by c9, t11-CLA. In vivo, dietary supplementation of c9, t11-CLA rather than t10, c12-CLA isomer decreased the expression of intestinal tight junction proteins and GPR120, increased intestinal permeability, and activated the MLCK signaling pathway in mice. Taken together, our findings showed that c9, t11-CLA, but not t10, c12-CLA isomer, impaired intestinal epithelial barrier function in IPEC-J2 cells and mice through activation of GPR120-[Ca2+]i and the MLCK signaling pathway. These data provided new insight into the regulation of the intestinal epithelial barrier by different CLA isomers and more references for CLA application in humans and animals.