Lanthanum nitrate inhibits adipogenesis in 3T3-L1 preadipocytes with a disorder of mitotic clonal expansion process.

Lanthanum (La) as a rare earth element is widely used in agriculture, industry, and medicine. It has been suggested in several studies that La might influence glycolipid metabolism in vivo. In this study, we used 3T3-L1 preadipocytes as in vitro cell model to elucidate the effects of La(NO3 )3 on adipogenesis and the underlying mechanisms. The results showed that La(NO3 )3 could inhibit the adipogenic differentiation of 3T3-L1 preadipocytes, which showed a decrease in lipid accumulation and the downregulation of specific adipogenic transcription factors. La(NO3 )3 exerted its inhibitory effect mainly at the early differentiation stage. Furthermore, La(NO3 )3 influenced the S-phase entry and cell cycle process during the mitotic clonal expansion and regulated the phosphorylation of signal transducer and activator of transcription 3 (STAT3) and expressions of the proteins in phosphatidylinositol 3-kinase (PI3K)/Akt pathway at the early stage of differentiation. Besides, La(NO3 )3 upregulated the expressions of wnt10b mRNA and ß-catenin protein and promoted the nucleus translocation of ß-catenin. Additionally, we found that La(NO3 )3 could promote the growth of 3T3-L1 preadipocytes both with and without MDI (3-isobutyl-1-methylxanthine [IBMX], dexamethasone [Dex], and insulin) stimulation. Collectively, these results indicated that La(NO3 )3 could inhibit adipogenesis in 3T3-L1 preadipocytes and influence cell proliferation.

Chlorocholine chloride induced testosterone secretion inhibition mediated by endoplasmic reticulum stress in primary rat Leydig cells.

Chlorocholine chloride (CCC) is well acknowledged as a plant growth regulator and may be considered as a potential environmental endocrine disrupting chemical. In our previous studies, it was found that CCC exposure at a pubertal stage reduced the serum and testicular levels of testosterone, decreased the sperm motility and delayed the puberty onset. However, the molecular mechanisms of CCC-induced testosterone secretion disorders remain unclear. In this study, we found that CCC exposure above 20 µg/mL inhibited the secretion of testosterone in Sprague-Dawley rats Leydig cells. Proteomic and pathway enrichment analysis indicated that CCC might induce endoplasmic reticulum (ER) stress. Western blot detection showed CCC exposure at 100, 200 µg/mL increased the protein level of glucose-regulated protein 78 (GPR78), C/EBP-homologous protein (CHOP), the ubiquitin-conjugating enzyme E2 D1 (UBE2D1) and the ring finger protein (RNF185) in the Leydig cells. The Leydig cells treated with 4-phenyl butyric acid (4-PBA), an ER stress inhibitor, rescued the testosterone secretion disorders and alleviated CCC-induced increase in the ER stress related protein levels at 200 µg/mL CCC treatment. Overall, CCC in vitro exposure might disturb testosterone production of Leydig cells and endoplasmic reticulum stress was involved in it.