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- Title
Liraglutide Lowers Body Weight Set Point in DIO Rats and its Relationship with Hypothalamic Microglia Activation.
- Authors
Liao, Ting; Zhang, Shan‐Lei; Yuan, Xue; Mo, Wen‐Qing; Wei, Fang; Zhao, Sheng‐Nan; Yang, Wei; Liu, Hong; Rong, Xi; Zhang, Shan-Lei; Mo, Wen-Qing; Zhao, Sheng-Nan
- Abstract
<bold>Objective: </bold>This study aimed to investigate the effects of liraglutide on the body weight set point (BWSP) in diet-induced obese rats and to determine the relationship between BWSP and hypothalamic arcuate nucleus (ARC) microglial activation.<bold>Methods: </bold>Diet-induced obesity (DIO) rats were divided into three groups: continuous high-fat diet (HFD) plus saline, HFD with liraglutide, and HFD with liraglutide pair feeding. Body weight, BWSP, inflammatory cytokines, suppressor of cytokine signaling 3, orexigenic/anorexigenic proteins, apoptosis, and microglia in the ARC were assessed. The effect of liraglutide on the Notch-1 signaling pathway and its relationships with nuclear factor-κB and p38 mitogen-activated protein kinase were also investigated in a lipopolysaccharide (LPS)-induced microglia activation model.<bold>Results: </bold>Liraglutide reduced BWSP; reversed adverse changes in hypothalamic inflammation, suppressor of cytokine signaling 3, and apoptosis; and diminished microgliosis in DIO rats. The BWSP showed a linear correlation with ARC microglial density. Liraglutide inhibited LPS-induced M1 microglial polarization and promoted microglial polarization to the M2 phenotype, diminishing inflammatory cytokine expression. Liraglutide inhibited Notch-1 signaling pathway activation and decreased nuclear factor-κB and p38 mitogen-activated protein kinase pathway activation in LPS-stimulated microglia.<bold>Conclusions: </bold>Liraglutide can reduce BWSP in DIO rats. There is a linear correlation between hypothalamic microgliosis and BWSP. Liraglutide reduces excessive microglial activation and inflammation, which may contribute to BWSP reduction.
- Subjects
BODY weight; POINT set theory; MICROGLIA; CONTINUOUS groups; RATS; APPETITE stimulants; MITOGEN-activated protein kinases
- Publication
Obesity (19307381), 2020, Vol 28, Issue 1, p122
- ISSN
1930-7381
- Publication type
journal article
- DOI
10.1002/oby.22666