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Unlocking the Potential of Obestatin: A Novel Peptide Intervention for Skeletal Muscle Regeneration and Prevention of Atrophy

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Abstract

Obestatin is derived from the same gene as that of ghrelin and their functions were perceived to be antagonistic. Recent developments have shown that although they are known to have contradictory functions, effect of obestatin on skeletal muscle regeneration is similar to that of ghrelin. Obestatin works through a receptor called GPR39, a ghrelin and motilin family receptor and transduces signals in skeletal muscle similar to that of ghrelin. Not only there is a similarity in the receptor family, but also obestatin targets similar proteins and transcription factors as that of ghrelin (for example, FoxO family members) for salvaging skeletal muscle atrophy. Moreover, like ghrelin, obestatin also works by inducing the transcription of Pax7 which is required for muscle stem cell mobilisation. Hence, there are quite some evidences which points to the fact that obestatin can be purposed as a peptide intervention to prevent skeletal muscle wasting and induce myogenesis. This review elaborates these aspects of obestatin which can be further exploited and addressed to bring obestatin as a clinical intervention towards preventing skeletal muscle atrophy and sarcopenia.

Graphical Abstract

Summary of action of obestatin in skeletal muscle atrophy. (Icon image source: www.flaticon.com; Obestatin structure: PDB id 2JSH)

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Data Availability

This is a review article. All the data used in the study have been accumulated from the cited references in the article.

Abbreviations

GPR39:

G protein-coupled receptor 39

Akt:

Protein Kinase B

PI3K:

Phosphoinositide 3-kinase

mTOR:

Mammalian Target of Rapamycin

MAPK:

Mitogen-Activated Protein Kinase

GHSR:

Growth Hormone Secretagogue Receptor

GH:

Growth Hormone

STZ:

Streptozotocin

PGC-1α:

Peroxisome proliferator-activated receptor-gamma coactivator-1α

IGF1:

Insulin-like Growth Factor

FoxO:

Forkhead family of transcription factors

CaMK II:

Calcium-calmodulin-dependent protein kinase II

KLF15:

Krüppel-like Factor 15

AMPK:

AMP-activated Protein Kinase

LC3:

Light Chain 3

AG:

Acylated Ghrelin

UAG:

Unacylated Ghrelin

Ub:

Ubiquitin

4E-BP1:

4E-binding protein 1

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Acknowledgements

The authors would also like to thank Yenepoya Research Centre, Yenepoya, deemed to be University, for providing the online library resources for writing this review article.

Funding

This research was funded by the Department of Biotechnology (BT/PR39858/MED/30/2247/2020) Government of India and awarded to the corresponding author.

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  1. Akash Mitra and Samanwita Mandal have contributed equally to this work.

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  1. Stem Cells and Regenerative Medicine Centre, Yenepoya Research Centre, Yenepoya (Deemed to Be University), Deralakatte, Mangalore, Karnataka, 575018, India

    Akash Mitra, Samanwita Mandal, Bipasha Bose & Sudheer Shenoy P

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  1. Akash Mitra
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AM and SM contributed to writing the paper. AM conceived the artwork. BB and SSP contributed to correcting the text and finalising the manuscript. All authors read and approved the manuscript.

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Correspondence to Sudheer Shenoy P.

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Mitra, A., Mandal, S., Bose, B. et al. Unlocking the Potential of Obestatin: A Novel Peptide Intervention for Skeletal Muscle Regeneration and Prevention of Atrophy. Mol Biotechnol 66, 948–959 (2024). https://doi.org/10.1007/s12033-023-01011-7

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