Molecular mechanisms of decidualization have been studied

Molecular mechanisms of decidualization have been studied for years, revealing numerous signaling pathways and transcriptional factors participated in the regulation [37,38]. As a central controller of deicdualization, FOXO1 regulates the transcription of a large number of target genes, which are involved in differentiation, proliferation and carry around [39,40]. Although the mutual regulation between FOXO1 and metabolism has been mentioned [41,42], the concrete roles and mechanisms remain to be further explored. In the current study, we found that ERK1/2-AMPK pathway was activated by GPR120 signaling and upregulated the expression of FOXO1. Moreover, GLUT1 was positively regulated by FOXO1, indicating that the effect of GPR120 on glucose uptake and thereby decidualization was mediated by ERK1/2-AMPK-FOXO1 signaling pathway. However, how GPR120 activation drives G6PD and PPP remains to be elucidated in future study. Immunomodulation is one of the important functions of decidua [21]. Considering its anti-inflammatory effect, GPR120 can be expected to augment decidualization via its immunomodulatory function. DSCs express high level of chemokines to recruit dNK cells. Moreover, peripheral NK (pNK) cells could be educated by TGF-β and IL-15 of DSC-origin into dNK cell phenotype, which is the dominant DICs in decidua [7]. CXCL12 is the main chemokine that recruits immuno-resistant dNK cells [43]. In the current study, while CXCL12, together with IL-15 and TGF-β, was decreased by LPS, GPR120 activation could restore the levels of CXCL12, IL-15 and TGF-β and simultaneously inhibited inflammatory cytokines TNF-α and IL-1β, thereby reduce pro-inflammaroty reactions induced by LPS in DSCs. Altogether, we demonstrate a positive role of GPR120 in decidualization possibly via regulating the immunomodulatory function of DSCs, which needed to be elucidated in future study.
Despite the fact that ischemia reperfusion injury and its effect on liver surgery have long been recognized, there are currently no available therapies to reliably prevent or reduce hepatic ischemia reperfusion injury (HIRI). Thus, HIRI continues to be a major barrier to liver surgery and transplantation , , , , particularly in steatotic livers , , , , . Intravenous (IV) fish oil (FO) is an injectable lipid emulsion rich in omega-3 fatty acids (O3FA) and the antioxidant α-tocopherol (vitamin E). The administration of a single dose of IV FO one hour before surgically-induced hepatic ischemia has been shown to reduce HIRI in a mouse model , . O3FA, particularly the biochemically active downstream fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are metabolized to anti-inflammatory and proresolving mediators , , . EPA and DHA also directly activate free fatty acid receptors, including the G-protein coupled receptor 120 (GPR120) (also known as free fatty acid receptor 4) , . Activation of GPR120 on macrophages, including hepatic Kupffer cells, inhibits proinflammatory signaling through the nuclear factor kappa-B (NFκB) and c-Jun N-terminal kinase (JNK) pathways , . A study by Raptis et al. suggested that activation of GPR120 on hepatic Kupffer cells is the mechanism that mediates FO's ability to reduce HIRI . However, this study used a synthetic, nonspecific free fatty acid receptor agonist (GW9508) and also used clodronate to deplete Kupffer cells to come to this conclusion . Kupffer cells are critical in initiating HIRI, so their depletion may have additional, GPR120-independent, effects . Thus, experiments using congenic GPR120 knockout (KO) mice are needed to fully examine its role.
Introduction Obesity is at record levels [1], and therefore, any advancement in understanding the relationship between physical activity and balanced nutrition beyond simple energy expenditure or calorie restriction could provide huge benefits in this area. Studies have shown, for example, the ability of nutrients, such as omega-3 (ω3), and physical exercise to reduce inflammation and endoplasmic reticulum stress in hypothalamus, partially restoring food intake control [2], [3] and modulating the peripheral inflammatory state [4], which contributes to the improvement of insulin resistance and glucose clearance.