Transgenic expression of myostatin propeptide prevents diet-induced obesity and insulin resistance
Abstract
Obesity and insulin resistance cause serious consequences to human health. To study effects of skeletal muscle growth on obesity prevention, we focused on a key gene of skeletal muscle named myostatin, which plays an inhibitory role in muscle growth and development. We generated transgenic mice through muscle-specific expression of the cDNA sequence (5'-region 886 nucleotides) encoding for the propeptide of myostatin. The transgene effectively depressed myostatin function. Transgenic mice showed dramatic growth and muscle mass by 9 weeks of age. Here we reported that individual major muscles of transgenic mice were 45-115% heavier than those of wild-type mice, maintained normal blood glucose, insulin sensitivity, and fat mass after a 2-month regimen with a high-fat diet (45% kcal fat). In contrast, high-fat diet induced wild-type mice with 170-214% more fat mass than transgenic mice and developed impaired glucose tolerance and insulin resistance. Insulin signaling, measured by Akt phosphorylation, was significantly elevated by 144% in transgenic mice over wild-type mice fed a high-fat diet. Interestingly, high-fat diet significantly increased adiponectin secretion while blood insulin, resistin, and leptin levels remained normal in the transgenic mice. The results suggest that disruption of myostatin function by its propeptide favours dietary fat utilization for muscle growth and maintenance. An increased secretion of adiponectin may promote energy partition toward skeletal muscles, suggesting that a beneficial interaction between muscle and adipose tissue play a role in preventing obesity and insulin resistance.
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Transgenic mice expressing non-functional myostatin conditioned to skeletal muscle show increased muscle mass and resistance to weight gain (fat mass) and insulin resistance even on a high-fat diet.
“Transgenic mice that expressed non-functional myostatin (conditioned to SkM), presented not only increased muscle mass but also resistance to weight gain (fat mass) and insulin resistance even when receiving a high-fat diet (Zhao et al., 2005).”
From Physical Exercise-Induced Myokines and Muscle-Adipose Tissue Crosstalk: A Review of Current Knowledge and the Implications for Health and Metabolic Diseases (2018) · cites this paper as Zhao et al., 2005
Mice deficient for myostatin show an improved metabolic phenotype and a resistance to HFD.
“Importantly, the inhibition of myostatin signaling increases PGC1α and mitochondrial biogenesis 145, while mice deficient for myostatin show an improved metabolic phenotype and a resistance to HFD 146, 147.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [146]
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“Transgenic mice that expressed non-functional myostatin (conditioned to SkM), presented not only increased muscle mass but also resistance to weight gain (fat mass) and insulin resistance even when receiving a high-fat diet (Zhao et al., 2005).”
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- Authors
- Zhao, B., Wall, R. J., & Yang, J.
- Affiliations
- University of Hawaiʻi at Mānoa (US)
- Agricultural Research Service (US)
- Corresponding author
- Yang, Jinzeng
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2005-11
- Volume
- 337
- Issue
- 1
- Pages
- 248-255
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W1994270208
- Cited by
- 186
- References
- 46
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 7 · 2023: 6 · 2022: 10 · 2021: 10 · 2020: 4 · 2019: 12 · 2018: 8 · 2017: 15 · 2016: 8 · 2015: 16 · 2014: 9 · 2013: 12 · 2012: 9
- FWCI
- 3.14
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Hawai'i
- Hawaii Community Foundation
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- myostatin propeptide, myostatin, diet-induced obesity, insulin resistance, skeletal muscle growth, muscle mass, high-fat diet, adiponectin, Akt phosphorylation, insulin signaling, fat mass, transgenic mice
- MeSH terms
- Adipose Tissue, Animals, Dietary Fats, Hormones, Insulin Resistance, Mice, Transgenic, Obesity, Peptides, Protein Precursors, Gene Expression, Transforming Growth Factor beta, Muscle, Skeletal, Mice, Myostatin
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