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. 2025 May 16;17(10):1693.
doi: 10.3390/nu17101693.

A Novel Camel Milk-Derived Peptide LLPK Improves Glucose-Lipid Metabolism in db/ db Mice via PPAR Signaling Pathway

Binsong Han  1   2   3 , Yuhui Ye  1 , Cunzheng Zhang  1 , Lina Zhang  2   3 , Peng Zhou  2   3
Affiliations

A Novel Camel Milk-Derived Peptide LLPK Improves Glucose-Lipid Metabolism in db/ db Mice via PPAR Signaling Pathway

Binsong Han et al. Nutrients. .

Abstract

Background: Camel milk is considered to be an important source of bioactive peptides with potential anti-diabetic effects. However, the mechanism by which these active peptides exert their anti-diabetic effects is not clear. The aim of this study was to systematically evaluate the in vivo anti-diabetic effects of Leucine-Leucine-Proline-Lysine (LLPK), a novel dipeptidyl peptidase-4 (DPP-4) inhibitory peptide identified from the in vitro gastrointestinal digestion product of camel milk. Methods: A db/db diabetic mouse model was used, and LLPK was administered to mice at doses of 50 mg/kg BW and 100 mg/kg BW as a daily oral gavage for 30 days. The effects of LLPK on fasting blood glucose (FBG), oral glucose tolerance test (OGTT), insulin tolerance test (ITT), and serum lipid levels were monitored, and possible mechanisms of action were elucidated using proteomics. Results: The results demonstrated that LLPK significantly improved diabetic symptoms, including FBG, OGTT, ITT, and serum lipid levels in db/db diabetic mice. Furthermore, significantly increased levels of serum glucagon-like peptide 1 (GLP-1) and reduced serum DPP-4 activity were observed in the LLPK-treated group compared to the control group. Hepatic proteomics indicated that LLPK improved glucose and lipid metabolism via the PPAR signaling pathway, where the key targets were Scd1, Acox1, Acaa1b, Slc27a1, Acsl1, and Ehhadh. Conclusions: In summary, this study provided new insights into the anti-diabetic mechanisms of camel milk and supported the development of camel milk-based anti-diabetic functional foods or nutraceuticals.

Keywords: PPAR signaling pathway; camel milk-derived peptide; diabetes; hepatic proteome.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Effect of LLPK treatment on (A) body weight, (B) diet consumption, (C) water consumption, and (D) FBG in db/db mice (the letter superscripts indicate the significant differences among samples based on ANOVA analysis, p < 0.05).
Figure 2
Figure 2
Effect of LLPK treatment on the glycemic homeostasis of db/db mice. (A) OGTT curves, (B) AUCs of OGTT, (C) ITT curves, and (D) AUCs of ITT (the letter superscripts indicate the significant differences among samples based on ANOVA analysis, p < 0.05).
Figure 3
Figure 3
Effect of LLPK treatment on (A) liver/body weight and (B–F) liver histopathological injury of db/db mice (the letter superscripts indicate the significant differences among samples based on ANOVA analysis, p < 0.05, and the black arrows represent fatty degeneration).
Figure 4
Figure 4
The effect of LLPK treatment on the hepatic proteome in db/db mice. (A) PCA analysis based on proteomics, (B) volcano plot between the NCG and DCG, and (C) volcano plot between the HPG and DCG (The green and red dots indicate down-regulated expression and up-regulated expression, respectively).
Figure 5
Figure 5
Bioinformatics analysis of the DEPs between the HPG and DCG. (A) KEGG pathway analysis of the DEPs and (B) PPI network analysis of the DEPs enriched in the PPAR signaling pathway.
Figure 6
Figure 6
The log2 protein intensity of (A) Scd1, (B) Acox1, (C) Acaa1b, (D) Slc27a1, (E) Acsl1, and (F) Ehhadh from the hepatic proteome (the letter superscripts indicate the significant differences among samples based on ANOVA analysis, p < 0.05).
Figure 7
Figure 7
The possible mechanism by which LLPK ameliorates lipid accumulation through the PPAR signaling pathway.
See this image and copyright information in PMC

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