The Tilapia collagen peptide mixture TY001 protects against LPS-induced inflammation, disruption of glucose metabolism, and aberrant expression of circadian clock genes in mice

ABSTRACT

The Tilapia collagen peptide mixture TY001 has been shown to accelerate wound healing in streptozotocin-induced diabetic mice and to protect against streptozotocin-induced inflammation and elevation in blood glucose. The goals of the present study are to further study TY001 effects on lipopolysaccharide (LPS)-induced inflammation and metabolic syndrome. LPS is known to disrupt circadian clock to produce toxic effects, the effects of TY001 on rhythmic alterations of serum cytokines and hepatic clock gene expressions were examined. Mice were given TY001 (30 g/L, ≈ 40 g/kg) through the drinking water for 30 days, and on the 21^st day of TY001 supplementation, LPS (0.25 mg/kg, ip, daily) was given for 9 days to establish the inflammation model. Repeated LPS injections produced inflammation, impaired glucose metabolism, and suppressed the expression of circadian clock core genes Bmal1 and Clock; clock feedback gene Cry1, Cry2, Per1, and Per2; clock target gene Rev-erbα and RORα. TY001 prevented LPS-induced elevations of TNFα, IL-1β, IL-6, and IL-10 in the liver, along with improved histopathology. TY001 reduced LPS-elevated fasting blood glucose and increased LPS-reduced serum insulin levels, probably via increased glucose transporter GLUT2, enhanced insulin signaling p-Akt and p-IRS-1^Try612. Importantly, LPS-induced circadian elevations of serum TNFα and IL-1β and aberrant expression of circadian clock genes in the liver were ameliorated by TY001. Immunohistochemistry revealed that the LPS decreased Bmal1 and Clock protein in the liver, which was recovered by TY001. Taken together, TY001 is effective against LPS-induced inflammation, disruption of glucose metabolism and disruption of circadian clock gene expressions.

Abbreviations: TY001: Tilapia collagen peptide mixture; LPS: Lipopolysaccharide; TNFα: Tumor necrosis factor-α; IL-1β: Interleukin-1β; GLUT2: Glucose transporter 2

KEYWORDS:

• The collagen-peptide mixture TY001
• LPS
• inflammation
• glucose metabolism
• circadian rhythm
• circadian clock gene expression

Acknowledgements

The samples of TY001 are provided by Yabao Pharmaceutical Group Co, Ltd. (Shanxi, China).

Author Contributions

X-Y.X., and Y.L. conceived and designed the experiments; X-Y.X., J.L, and Y.X. performed the experiments; X-Y.X., J.L. and Y.L. analyzed the data; X-Y.X. and Y.L. wrote the paper.

Conflicts of Interest

The authors declare no conflict of interest.

Supplementary material

supplemental data for this article can be accessed here

Additional information

Funding

This work was supported by the National Key Research and Development Program of China [2016YFD0400602].