Rxivist logo

Leptin Receptors in RIP-Cre25Mgn neurons Mediate Anti-Dyslipidemia Effects of Leptin in Insulin-Deficient Male Mice

By Ashish Singha, Juan Pablo Palavicini, Meixia Pan, Darleen Sandoval, Xianlin Han, Teppei Fujikawa

Posted 14 Mar 2020
bioRxiv DOI: 10.1101/2020.03.13.989442 (published DOI: 10.3389/fendo.2020.588447)

Leptin is a potent endocrine hormone produced by adipose tissue and regulates a broad range of metabolism including glucose and lipid metabolism, with and without insulin. It is evident that central leptin signaling can lower hyperglycemia in insulin-deficient rodents via multiple mechanisms including restoration of dyslipidemia. However, the specific neurons that regulate these glucose-lowering and 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-Cre25Mgn neurons) are required for central leptin signaling to reverse hyperglycemia and dyslipidemia in insulin-deficient mice. Ablation of LEPRs in RIP-Cre25Mgn neurons completely blocks glucose-lowering effects of leptin in insulin-deficient mice. Further investigations reveal that insulin-deficient mice lacking LEPRs in RIP-Cre25Mgn 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 insulin-deficient RIP-Cre∆LEPR mice. Collectively, our data demonstrate that LEPRs in RIP-Cre25Mgn neurons significantly contribute to glucose-lowering effects of leptin in an insulin-independent manner by suppression of dyslipidemia.

Download data

  • Downloaded 120 times
  • Download rankings, all-time:
    • Site-wide: 110,913
    • In neuroscience: 17,220
  • Year to date:
    • Site-wide: None
  • Since beginning of last month:
    • Site-wide: 108,060

Altmetric data

Downloads over time

Distribution of downloads per paper, site-wide


Sign up for the Rxivist weekly newsletter! (Click here for more details.)