.png){kind=icon}
.png){kind=icon}
Return
The anti-obesity and hepatoprotective effects of bacterial cyclodipeptides in a rat obesity model involve aquaporins, inflammatory factors, and GAB1 modulation
.png){kind=icon}
PRE
AI
C
R
M
L
J
DOI：10.1007/s13105-026-01223-w.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Obesity is a major risk factor for Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) and its progressive form, Metabolic Dysfunction-Associated Steatohepatitis (MASH). Bacterial cyclodipeptides (CDPs) have previously been shown to modulate PI3K/Akt/mTOR signaling and transcriptional programs involved in lipid and cholesterol metabolism, highlighting their potential to regulate metabolic homeostasis. Given the central role of the PI3K/Akt/FoxO1 pathway in regulating aquaporins, inflammatory cytokines, and metabolic homeostasis during obesity and MASLD, the therapeutic potential of CDPs was evaluated in a rat model of MASLD. Treatment of obese animals with CDPs decreased body weight and abdominal and thoracic circumferences. The obesogenic diet induced liver damage after the 34th week, which was alleviated by ten weeks of CDP treatment administered three times a week. This reduced the number and size of lipid droplets and inflammatory infiltrates. Additionally, CDPs improved parameters associated with atherogenic dyslipidemia and metabolic dysfunction, including triglycerides and cholesterol, as well as hepatic injury markers. These changes were accompanied by restoration of mitochondrial membrane potential and a significant reduction in mitochondrial ROS generation. CDP treatment in obese animals restored protein expression levels of aquaporins AQP1, AQP5, AQP8, and AQP9 and downregulated the expression of the inflammatory markers NF-κB and IL-1β. Interestingly, the downstream cellular mediator GAB1 from the PI3K/Akt/FoxO1 pathway was also downregulated. These findings demonstrate that CDP treatment restored the expression of glycerol/water transporting aquaporins altered during obesity and MASLD. Overall, CDPs ameliorated MASLD in obese animals through coordinated modulation of lipid metabolism, mitochondrial function, aquaporin expression, and PI3K/Akt/FoxO1 signaling associated with inflammation, supporting their potential as therapeutic candidates for metabolic liver disease. Anti-obesity and hepatoprotective effects of CDPs. Anti-obesity mechanism of CDPs involves the expression of aquaporins. CDPs modulate the expression of the NF-κB, IL-1β factors, and GAB1 factor.
Keywords:
Anti-obesity drugs
MASLD
Hepatoprotection
Cyclodipeptides
Aquaporins
GAB1
Journal
IF:
4.3
Papers:
1.7K
Citations:
2.7K