Shatavari supplementation in postmenopausal women alters the skeletal muscle proteome and pathways involved in training adaptation

O’Leary, Mary F.; Jackman, Sarah R.; Bowtell, Joanna L.

doi:10.1007/s00394-023-03310-w

Cited by 3 publications

(1 citation statement)

References 51 publications

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“…Rbm20 (accession Q3UQS8), which regulates post-transcriptional splicing of sarcomeric and other muscle homeostasis genes, was downregulated in OVX compared to Sham muscle (Figure 3A & A I ; p <0.0001). To understand whether OVX impacts families of proteins, which were not detected as significant due to the log 2 fold change cutoff and p value criteria, pathway analysis (via Reactome) of the entire proteome dataset was conducted 42 . A total of 59 pathways were impacted by OVX (Figure 3B).…”

Section: Resultsmentioning

confidence: 99%

Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in femalemdxmice

Timpani,

Debrincat,

Kourakis

et al. 2024

Preprint

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Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT-labelling. Our study confirms that loss of estrogen in female mdx mice reduces exercise capacity, tricarboxylic acid cycle intermediates and citrate synthase activity but that these deficits can be offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggests that estrogen mitigates dystrophinopathic features in female mdx mice and that estrogen replacement may be a potential therapy for post-menopausal DMD carriers.

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Section: Resultsmentioning

confidence: 99%

Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in femalemdxmice

Timpani,

Debrincat,

Kourakis

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock‐related protein Rbm20 in female mdx mice

Timpani,

Debrincat,

Kourakis

et al. 2024

The FASEB Journal

View full text Add to dashboard Cite

Female carriers of a Duchenne muscular dystrophy (DMD) gene mutation manifest exercise intolerance and metabolic anomalies that may be exacerbated following menopause due to the loss of estrogen, a known regulator of skeletal muscle function and metabolism. Here, we studied the impact of estrogen depletion (via ovariectomy) on exercise tolerance and muscle mitochondrial metabolism in female mdx mice and the potential of estrogen replacement therapy (using estradiol) to protect against functional and metabolic perturbations. We also investigated the effect of estrogen depletion, and replacement, on the skeletal muscle proteome through an untargeted proteomic approach with TMT‐labelling. Our study confirms that loss of estrogen in female mdx mice reduces exercise capacity, tricarboxylic acid cycle intermediates, and citrate synthase activity but that these deficits are offset through estrogen replacement therapy. Furthermore, ovariectomy downregulated protein expression of RNA‐binding motif factor 20 (Rbm20), a critical regulator of sarcomeric and muscle homeostasis gene splicing, which impacted pathways involving ribosomal and mitochondrial translation. Estrogen replacement modulated Rbm20 protein expression and promoted metabolic processes and the upregulation of proteins involved in mitochondrial dynamics and metabolism. Our data suggest that estrogen mitigates dystrophinopathic features in female mdx mice and that estrogen replacement may be a potential therapy for post‐menopausal DMD carriers.

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Effects of the DailyColors™ Polyphenol Supplement on Serum Proteome, Cognitive Function, and Health in Older Adults at Risk of Cognitive and Functional Decline

O’Leary,

Bowtell,

Richards

et al. 2024

Preprint

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The Mediterranean diet is associated with reduced mortality and cognitive decline, largely due to its polyphenol content. However, Western populations often do not meet recommended fruit and vegetable intakes. Polyphenols exert anti-inflammatory effects and may influence extracellular vesicle (EV) dynamics. DailyColors™ is a polyphenol-rich blend inspired by the Mediterranean Diet, containing extracts from 16 fruits, vegetables, and herbs. This 60-day, double-blind, placebo-controlled, randomised trial involved 150 UK adults aged 50+ with a BMI ≥ 25, recruited to complete cognitive and physical fitness assessments via the PROTECT-UK online platform. Participants received either a medium (750mg) or high (2000mg) dose of DailyColors™ (~300mg and ~750mg polyphenols, respectively) or a placebo. A sub-group (n=15 per group) underwent additional assessments, including blood pressure measurements, characterisation of circulating EVs and tandem-mass-tagged serum proteomics. Significant cognitive benefits were observed, with improvements in reaction time for the high-dose group and accuracy for both active supplement groups. The high-dose group also showed significant physical fitness gains on the Timed Stand Test (P<0.001). All groups improved on the Chair Stand Test. Proteomic analysis showed significantly reduced serum protein expression in immune and pre-β1-HDL pathways, suggesting anti-inflammatory effects. Pre-β1-HDL proteins are typically elevated in obesity; their reduction suggests a reversal of this obesity-related effect. No significant changes were noted in EV concentration or size. DailyColors™ supplementation, may enhance cognitive function, physical fitness, and systemic health in older, overweight adults, potentially mimicking the anti-inflammatory effects of the Mediterranean diet. These findings warrant investigation in larger trials.

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Shatavari supplementation in postmenopausal women alters the skeletal muscle proteome and pathways involved in training adaptation

Cited by 3 publications

References 51 publications

Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in femalemdxmice

Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock-related protein Rbm20 in femalemdxmice

Loss of endogenous estrogen alters mitochondrial metabolism and muscle clock‐related protein Rbm20 in female mdx mice

Effects of the DailyColors™ Polyphenol Supplement on Serum Proteome, Cognitive Function, and Health in Older Adults at Risk of Cognitive and Functional Decline

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