Resistance to body fat gain in ‘double-muscled’ mice fed a high-fat diet

Hamrick, Mark W.; Pennington, Catherine; Webb, Clinton; Isales, Carlos M.

doi:10.1038/sj.ijo.0803200

Cited by 53 publications

(45 citation statements)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Myostatin knock-out (KO) mice offered high-fat diets are resistant to gains in body fat [14], [15], and although this effect may be secondary to the increases in lean body mass, myostatin had direct effects on adipocyte differentiation [16], [17]. Furthermore, blocking myostatin increased the functional capacity of brown adipose tissue (BAT) [18] and may even drive the browning of white adipose tissue through the up-regulation of BAT-specific genes [19].…”

Section: Introductionmentioning

confidence: 99%

Preliminary Investigation into a Potential Role for Myostatin and Its Receptor (ActRIIB) in Lean and Obese Horses and Ponies

Morrison

Chen

Harris³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

Obesity is a widespread problem across the leisure population of horses and ponies in industrialised nations. Skeletal muscle is a major contributor to whole body resting energy requirements and communicates with other tissues through the secretion of myokines into the circulation. Myostatin, a myokine and negative regulator of skeletal muscle mass, has been implicated in obesity development in other species. This study evaluated gene and protein expression of myostatin and its receptor, ActRIIB in adipose tissues and skeletal muscles and serum myostatin concentrations in six lean and six obese animals to explore putative associations between these factors and obesity in horses and ponies. Myostatin mRNA expression was increased while ActRIIB mRNA was decreased in skeletal muscles of obese animals but these differences were absent at the protein level. Myostatin mRNA was increased in crest fat of obese animals but neither myostatin nor ActRIIB proteins were detected in this tissue. Mean circulating myostatin concentrations were significantly higher in obese than in lean groups; 4.98 ng/ml (±2.71) and 9.00 ng/ml (±2.04) for the lean and obese groups, respectively. In addition, there was a significant positive association between these levels and myostatin gene expression in skeletal muscles (average R2 = 0.58; p<0.05). Together, these results provide further basis for the speculation that myostatin and its receptor may play a role in obesity in horses and ponies.

show abstract

Section: Introductionmentioning

confidence: 99%

Preliminary Investigation into a Potential Role for Myostatin and Its Receptor (ActRIIB) in Lean and Obese Horses and Ponies

Morrison

Chen

Harris³

et al. 2014

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…In fact, in vitro studies with various mesenchymal adipocyte progenitor cells are again highly controversial because myostatin has been demonstrated to both inhibit and stimulate their differentiation into mature adipocytes (29 -33). Resolving this controversy has clinical implications because attenuating myostatin both prevents and reverses obesity in different animal models and can even improve insulin sensitivity (26,28,34,35). Thus, novel myostatinantagonizing therapeutics, which are currently being developed (36 -38), could potentially be used to treat type 2 diabetes in addition to muscle-related disorders.…”

mentioning

confidence: 96%

Myostatin Regulates Tissue Potency and Cardiac Calcium-Handling Proteins

Jackson

Rodgers

2014

Endocrinology

View full text Add to dashboard Cite

Attenuating myostatin enhances striated muscle growth, reduces adiposity, and improves cardiac contractility. To determine whether myostatin influences tissue potency in a manner that could control such pleiotropic actions, we generated label-retaining mice with wild-type and mstn(-/-) (Jekyll) backgrounds in which slow-cycling stem, transit-amplifying, and progenitor cells are preferentially labeled by histone 2B/green fluorescent protein. Jekyll mice were born with fewer label-retaining cells (LRCs) in muscle and heart, consistent with increased stem/progenitor cell contributions to embryonic growth of both tissues. Cardiac LRC recruitment from noncardiac sources occurred in both groups, but lasted longer in Jekyll hearts, whereas heightened β-adrenergic sensitivity of mstn(-/-) hearts was explained by elevated SERCA2a, phospholamban, and β2-adrenergic receptor levels. Jekyll mice were also born with more adipose LRCs despite significantly smaller tissue weights. Reduced adiposity in mstn(-/-) animals is therefore due to reduced lipid deposition as adipoprogenitor pools appear to be enhanced. By contrast, increased bone densities of mstn(-/-) mice are likely compensatory to hypermuscularity because LRC counts were similar in Jekyll and wild-type tibia. Myostatin therefore significantly influences the potency of different tissues, not just muscle, as well as cardiac Ca²⁺-handling proteins. Thus, the pleiotropic phenotype of mstn(-/-) animals may not be due to enhanced muscle development per se, but also to altered stem/progenitor cell pools that ultimately influence tissue potency.

show abstract

“…Furthermore, myostatin-null mice and myostatin propeptide-overexpressing Tg mice were used to study the effects of myostatin inhibition on obesity (10,14,24,41,42). These studies revealed that the inhibition of myostatin decreased adipose tissue accumulation and improved diet-induced obesity and genetic diabetes/obesity.…”

Section: Discussionmentioning

confidence: 99%

“…The loss of myostatin by gene disruption prevents an agerelated increase in adipose tissue mass and partially attenuates the obese and diabetic phenotypes (14,24). The serum leptin concentration and adipose tissue leptin mRNA expression were lower in myostatin null mice than in wild-type mice (24).…”

mentioning

confidence: 95%