Leptin is a potent endocrine hormone produced by adipose tissue and regulates a broad range of whole-body metabolism such as glucose and lipid metabolism, even without insulin. Central leptin signaling can lower hyperglycemia in insulin-deficient rodents via multiple mechanisms, including improvements of dyslipidemia. However, the specific neurons that regulate anti-dyslipidemia effects of leptin remain unidentified. Here we report that leptin receptors (LEPRs) in neurons expressing Cre recombinase driven by a short fragment of a promoter region of Ins2 gene (RIP-Cre 25Mgn neurons) are required for central leptin signaling to reverse dyslipidemia, thereby hyperglycemia in insulin-deficient mice. Ablation of LEPRs in RIP-Cre 25Mgn neurons completely blocks glucose-lowering effects of leptin in insulin-deficient mice. Further investigations reveal that insulin-deficient mice lacking LEPRs in RIP-Cre 25Mgn neurons (RIP-Cre LEPR mice) exhibit greater lipid levels in blood and liver compared to wild-type controls, and that leptin injection into the brain does not suppress dyslipidemia in insulin-deficient RIP-Cre LEPR mice. Leptin administration into the brain combined with acipimox, which lowers blood lipids by suppressing triglyceride lipase activity, can restore normal glycemia in insulin-deficient RIP-Cre LEPR mice, suggesting that excess circulating lipids are a driving-force of hyperglycemia in these mice. Collectively, our data demonstrate that LEPRs in RIP-Cre 25Mgn neurons significantly contribute to glucose-lowering effects of leptin in an insulin-independent manner by improving dyslipidemia.
Melanoma is a predominant cause of skin cancer-related deaths. It was reported that, the methanolic extract of Pouzolzia Indica (P. indica) on chromatography gave five compounds (1-hentriacontanyl palmitate, myricyl alcohol, 6,7-dimethoxycoumarin, trichadonic acid and friedelane), which inhibited the acute promyelocytic leukemia cell lines, NB4, and HT93A. Friedelane was extracted as active compound from methanolic extract of P. indica. In this study, friedelane was tested on murine metastatic B16F10 and B16BL6 melanoma cell lines. To achieve the target, the cell viability using trypan blue exclusion, acridine orange/EtBr staining and cell cytotoxicity were tested using MTT assay. Caspase-3, caspase-9, Cyt-c, BAD and Bax protein were assayed to evidence the apoptosis induction. The compound friedelane shows potent cytotoxic effect against metastatic melanoma mouse cell lines in 10 µg/ml concentration.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.