The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models
Abstract
:1. Introduction
2. Materials and Methods
2.1. Peptide Drug Candidates
2.2. Animals, Treatments, and Tissue Processing
2.3. Feed
2.4. Cell Culture
2.5. RNA Isolation and Reverse Transcription–Quantitative Polymerase Chain Reaction (RT-qPCR) Protocol
2.6. Immunohistochemistry of Phosphorylated STAT3 (p-STAT3) in Mouse Hypothalamus
2.7. Serum Glucose, Insulin, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR)
2.8. WB Analysis
2.9. Evaluation of the Proinflammatory Cytokine Tumor Necrosis Factor Alpha (TNFα) in Serum
2.10. Free-Feeding Food Intake Experiment in Mice
2.11. OGTT
2.12. Histology
2.13. Statistical Analysis
3. Results
3.1. In Vitro Screening for Novel Regulatory Peptides to Treat Metabolic Disorders
3.2. Free-Feeding Food Intake and Hypothalamic STAT3 Activity Regulation by CHM-273S
3.3. Glucose Tolerance, Insulin Resistance, and Liver Insulin Signaling Alterations Induced by the HSD and the Acute CHM-273S Treatment Effects
3.4. Glucose Tolerance, Insulin Resistance, and Systemic Inflammation in HFD-Fed Mice and the Effects of Chronic CHM-273S Treatment
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Amino Acid Sequence | Source of Peptide | ||
---|---|---|---|
SKDIGSESTEDQAME | CasA1 | CHM-273 fragments | |
REQLSTSEEN | CasA2 | Amino acid sequence | |
NKKIEKF | CasB | DLSKEP | |
VQVTSTAV | CasK | SISRE | |
LIVTQTMKGLD | LacB | SKEPSIS (CHM-273L) | |
WENGECAQK | LacB | DLSK | |
DLSKEPSISRE (CHM-273) | GlyCam1 | LSKE | |
NKPEDETHL | GlyCam1 | → | SKEP |
FEVVKT | GlyCam1 | ISRE | |
NLENTVK | GlyCam1 | PSIS | |
AGGPGAPADPGRPT | PIGR | SISR | |
SNVQSPD | OSTP | EPSI (CHM-273S) | |
SHIESEEMHD | OSTP | KEPS | |
HKSEEDKHL | OSTP |
DAY OF EXPERIMENT | BODY WEIGHT (G) | BLOOD GLUCOSE (MMOL/L) | ||||||
---|---|---|---|---|---|---|---|---|
Control (n = 5) | HSD (n = 45) | Control (n = 5) | HSD (n = 45) | |||||
0 | 402.2 | ±27.8 | 415.0 | ±33.6 | ||||
8 | 431.2 | ±26.0 | 434.3 | ±35.6 | 4.8 | ±0.2 | 4.7 | ±0.4 |
15 | 436.6 | ±30.2 | 451.5 | ±41.3 | 5 | ±0.7 | 4.7 | ±0.5 |
22 | 449 | ±25.6 | 452.1 | ±44.3 | 5.3 | ±0.6 | 5.4 ab | ±0.6 |
28 | 456.4 | ± 24.0 | 467.0 | ± 47.7 | 5.4 | ± 0.6 | 6.1 * abc | ± 0.5 |
WEEKS | CONTROL (N = 25) | HFD (N = 100) | ||
---|---|---|---|---|
0 | 20.5 | ±1 | 20.1 | ±1.1 |
16 | 28.9 | ±1.6 | 37.6 * | ±3.6 |
% OF WEIGHT GAIN | 41% | ±7.8% | 87.5% | ±20.1% |
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Mitkin, N.A.; Pavshintcev, V.V.; Sukhanova, I.A.; Doronin, I.I.; Babkin, G.A.; Sadagurski, M.; Malyshev, A.V. The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models. Pharmaceutics 2022, 14, 2088. https://doi.org/10.3390/pharmaceutics14102088
Mitkin NA, Pavshintcev VV, Sukhanova IA, Doronin II, Babkin GA, Sadagurski M, Malyshev AV. The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models. Pharmaceutics. 2022; 14(10):2088. https://doi.org/10.3390/pharmaceutics14102088
Chicago/Turabian StyleMitkin, Nikita A., Vsevolod V. Pavshintcev, Iuliia A. Sukhanova, Igor I. Doronin, Gennady A. Babkin, Marianna Sadagurski, and Anton V. Malyshev. 2022. "The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models" Pharmaceutics 14, no. 10: 2088. https://doi.org/10.3390/pharmaceutics14102088
APA StyleMitkin, N. A., Pavshintcev, V. V., Sukhanova, I. A., Doronin, I. I., Babkin, G. A., Sadagurski, M., & Malyshev, A. V. (2022). The Novel Peptide Chm-273s Has Therapeutic Potential for Metabolic Disorders: Evidence from In Vitro Studies and High-Sucrose Diet and High-Fat Diet Rodent Models. Pharmaceutics, 14(10), 2088. https://doi.org/10.3390/pharmaceutics14102088