Fast/Glycolytic Muscle Fiber Growth Reduces Fat Mass and Improves Metabolic Parameters in Obese Mice

Izumiya, Yasuhiro; Hopkins, Teresa A.; Morris, Carl; Sato, Kaori; Zeng, Ling; Viereck, Jason; Hamilton, James A.; Ouchi, Noriyuki; LeBrasseur, Nathan K.; Walsh, Kenneth

doi:10.1016/j.cmet.2007.11.003

Cited by 335 publications

(392 citation statements)

References 49 publications

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“…These data demonstrated an activation of the PI3K/Akt signalling pathway in response to MSTN loss-of-function in cattle as previously shown in mice. They are in agreement with data indicating a crucial role of this pathway in muscle hypertrophy (Glass, 2003) for example, increase in fibre size induced by constitutive activation of Akt (Pallafacchina et al, 2002) and hypertrophy of type IIb muscle fibres induced by muscle-specific Akt1 transgene expression (Izumiya et al, 2008).…”

Section: Discussionsupporting

confidence: 92%

Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Chelh

Picard

Hocquette

et al. 2011

Animal

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Myostatin (MSTN), a member of the TGF-b superfamily, is a negative regulator of skeletal muscle mass. We have previously shown that the cell survival/apoptosis pathway is a downstream target of MSTN loss-of-function in mice through the regulation of the expression or abundance of many survival and apoptotic factors. In this study, we used western-blot and quantitative PCR (qPCR) analyses to validate these novel downstream targets of MSTN in double-muscled (DM) cattle v. their controls including 260-day-old foetuses and adult cows from the INRA95 strain. MSTN loss-of-function in DM foetuses and DM cows resulted in a glycolytic shift of the muscles (e.g. upregulation of H-MyBP, PGM1 and SNTA1 and downregulation of H-FABP), activation of cell survival pathway through regulation of some components of the PI3K/Akt pathway (e.g. upregulation of DJ-1 and Gsk-3bser9/ Gsk-3btotal ratio and downregulation of PTEN) and upregulation of cell survival factors translationally controlled tumour protein (14-3-3E, Pink1). We also found a lower abundance of pro-apoptotic transcripts and/or proteins (Caspase-3, caspase-8, caspase-9, BID, ID2 and Daxx) and a higher expression of anti-apoptotic transcripts (Traf2 and Bcl2l2) in DM muscles. All together, these results are in favour of activation of the cell survival pathway and loss of apoptosis pathway within the muscles of DM animals. Alteration of both pathways may increase myonuclear or satellite cell survival, which is crucial for protein synthesis. This could contribute to muscle hypertrophy in DM foetuses and DM cows.Keywords: myostatin, cattle, muscle hypertrophy, apoptosis, cell survival ImplicationsMuscle hypertrophy has been extensively studied in meatproducing animals. In double-muscled (DM) cattle, a loss-offunction mutation in the myostatin gene (MSTN ) is responsible for muscle hypertrophy. In order to get a thorough knowledge of the molecular mechanisms of MSTN action, we have examined the molecular phenotype of DM muscle based on our previous data in MSTN-null mice. The data bring new elements to the understanding of the DM muscle phenotype and of the regulation of muscle mass in farm animals.

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Section: Discussionsupporting

confidence: 92%

Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Chelh

Picard

Hocquette

et al. 2011

Animal

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“…Muscle-derived IL-6, but not IL-8, contributes markedly to systemic levels, where it works in a hormone-like fashion and plays an important role in lipid and glucose metabolism [9,10], principally via activation of AMP-activated protein kinase (AMPK) [10]. Recent studies from others, employing skeletal muscle-specific AKT1 transgenic [11] and muscle-specific peroxisome proliferator activated receptor gamma coactivator 1 alpha (PGC-1α) knockout [12] mice, have also observed altered metabolism in tissues such as pancreas, liver and adipose tissue. The authors of these respective papers hypothesised that musclederived circulatory factors or myokines may have been responsible for the observed tissue cross-talk.…”

Section: Introductionmentioning

confidence: 99%

Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

Matthews¹,

Åström

Chan³

et al. 2009

Diabetologia

533

452

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Aims/hypothesis Brain-derived neurotrophic factor (BDNF) is produced in skeletal muscle, but its functional significance is unknown. We aimed to determine the signalling processes and metabolic actions of BDNF. Methods We first examined whether exercise induced BDNF expression in humans. Next, C2C12 skeletal muscle cells were electrically stimulated to mimic contraction. L6 myotubes and isolated rat extensor digitorum longus muscles were treated with BDNF and phosphorylation of the proteins AMP-activated protein kinase (AMPK) (Thr 172 ) and acetyl coenzyme A carboxylase β (ACCβ) (Ser 79 ) were analysed, as was fatty acid oxidation (FAO).Finally, we electroporated a Bdnf vector into the tibialis cranialis muscle of mice. Results BDNF mRNA and protein expression were increased in human skeletal muscle after exercise, but muscle-derived BDNF appeared not to be released into the circulation. Bdnf mRNA and protein expression was increased in muscle cells that were electrically stimulated. BDNF increased phosphorylation of AMPK and ACCβ and enhanced FAO both in vitro and ex vivo. The effect of BDNF on FAO was AMPK-dependent, since the increase in FAO was abrogated in cells infected with an AMPK dominant negative adenovirus or treated with Compound C, an inhibitor of AMPK. Electroporation of a Bdnf expression

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“…A potential consequence of muscle hypertrophy is increased anaerobic glycolysis, which could drive lactic acidemia. Indeed, such a phenotype was observed in mice with skeletal musclespecific expression of a constitutively active Akt1 (15). However, mice treated with ATA 842 did not display any increase in plasma lactate concentrations (Fig.…”

Section: Significancementioning

confidence: 93%

Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice

Camporez

Petersen

Abulizi

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

137

100

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Sarcopenia, or skeletal muscle atrophy, is a debilitating comorbidity of many physiological and pathophysiological processes, including normal aging. There are no approved therapies for sarcopenia, but the antihypertrophic myokine myostatin is a potential therapeutic target. Here, we show that treatment of young and old mice with an antimyostatin antibody (ATA 842) for 4 wk increased muscle mass and muscle strength in both groups. Furthermore, ATA 842 treatment also increased insulin-stimulated whole body glucose metabolism in old mice, which could be attributed to increased insulin-stimulated skeletal muscle glucose uptake as measured by a hyperinsulinemic-euglycemic clamp. Taken together, these studies provide support for pharmacological inhibition of myostatin as a potential therapeutic approach for age-related sarcopenia and metabolic disease.aging | myostatin | muscle mass | insulin resistance | sarcopenia

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Fast/Glycolytic Muscle Fiber Growth Reduces Fat Mass and Improves Metabolic Parameters in Obese Mice

Cited by 335 publications

References 49 publications

Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Myostatin inactivation induces a similar muscle molecular signature in double-muscled cattle as in mice

Brain-derived neurotrophic factor is produced by skeletal muscle cells in response to contraction and enhances fat oxidation via activation of AMP-activated protein kinase

Anti-myostatin antibody increases muscle mass and strength and improves insulin sensitivity in old mice

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