Circulating protein synthesis rates reveal skeletal muscle proteome dynamics

Shankaran, Mahalakshmi; King, Chelsea; Angel, Thomas E.; Holmes, William E.; Li, Kelvin W.; Colangelo, Marc; Price, John C.; Turner, Scott; Bell, Christopher; Hamilton, Karyn L.; Miller, Benjamin F.; Hellerstein, Marc K.

doi:10.1172/jci79639

Cited by 72 publications

(82 citation statements)

References 69 publications

(101 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…9) has not previously been captured and is a unique aspect of the current investigation. New techniques have recently been developed that incorporate D 2 O labeling with proteomic analyses, including peptide mass spectrometry, which measures the rate constant (k) for synthesis on a protein-by-protein basis in the muscle of animals (33)(34)(35)(36) and humans (20). Collectively, these works and our current data (Fig.…”

Section: Discussionmentioning

confidence: 77%

Dynamic proteome profiling of individual proteins in human skeletal muscle after a high‐fat diet and resistance exercise

Camera

Burniston²,

Pogson³

et al. 2017

The FASEB Journal

View full text Add to dashboard Cite

It is generally accepted that muscle adaptation to resistance exercise (REX) training is underpinned by contraction‐induced, increased rates of protein synthesis and dietary protein availability. By using dynamic proteome profiling (DPP), we investigated the contribution of both synthesis and breakdown to changes in abundance on a protein‐by‐protein basis in human skeletal muscle. Age‐matched, overweight males consumed 9 d of a high‐fat, low‐carbohydrate diet during which time they either undertook 3 sessions of REX or performed no exercise. Precursor enrichment and the rate of incorporation of deuterium oxide into newly synthesized muscle proteins were determined by mass spectrometry. Ninety proteins were included in the DPP, with 28 proteins exhibiting significant responses to REX. The most common pattern of response was an increase in turnover, followed by an increase in abundance with no detectable increase in protein synthesis. Here, we provide novel evidence that demonstrates that the contribution of synthesis and breakdown to changes in protein abundance induced by REX differ on a protein‐by‐protein basis. We also highlight the importance of the degradation of individual muscle proteins after exercise in human skeletal muscle.—Camera, D. M., Burniston, J. G., Pogson, M. A., Smiles, W. J., Hawley, J. A. Dynamic proteome profiling of individual proteins in human skeletal muscle after a high‐fat diet and resistance exercise. FASEB J. 31, 5478–5494 (2017). http://www.fasebj.org

show abstract

Section: Discussionmentioning

confidence: 77%

Dynamic proteome profiling of individual proteins in human skeletal muscle after a high‐fat diet and resistance exercise

Camera

Burniston²,

Pogson³

et al. 2017

The FASEB Journal

View full text Add to dashboard Cite

show abstract

“…Mixed-protein synthesis traditionally measured in skeletal muscle reflects an average rate of synthesis across all muscle proteins, whose individual rates, however, differ considerably within the skeletal muscle (Jaleel et al, 2008;Shankaran et al, 2016). Previous research has shown almost twofold higher synthesis rate of mixed-mitochondrial protein when compared to the synthesis rate of mixed-muscle protein in skeletal muscle of young, healthy humans (Rooyackers, Adey, Ades, & Nair, 1996).…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial ATP synthase β‐subunit production rate and ATP synthase specific activity are reduced in skeletal muscle of humans with obesity

Tran

Langlais

Hoffman

et al. 2018

Experimental Physiology

View full text Add to dashboard Cite

The content of the beta subunit of the ATP synthase (β-F1-ATPase), which forms the catalytic site of the enzyme ATP synthase, is reduced in muscle of obese humans, along with reduced capacity for ATP synthesis. We studied 18 young (37 ± 8 years old) subjects of which nine were lean (BMI = 23 ± 2 kg/m2) and nine were obese (BMI = 34 ± 3 kg/m2) to determine the fractional synthesis rate (FSR) and gene expression of β-F1-ATPase, as well as the specific activity of the ATP synthase. FSR of β-F1-ATPase was determined using a combination of isotope tracer infusion and muscle biopsies. Gene expression of β-F1-ATPase and specific activity of the ATP synthase were determined in the muscle biopsies. When compared to lean, obese subjects had lower muscle β-F1-ATPase FSR (0.10 ± 0.05 vs 0.06 ± 0.03 %/hr; P < 0.05) and protein expression (P < 0.05), but not mRNA expression (P > 0.05). Across subjects, abundance of β-F1-ATPase correlated with the FSR of β-F1-ATPase (P < 0.05). The specific activity of muscle ATP synthase was lower in the obese when compared to lean subjects (0.035 ± 0.004 vs 0.042 ± 0.007 arbitrary units; P < 0.05), but this difference was not significant after the activity of the ATP synthase was adjusted to the β-F1-ATPase content (P > 0.05). Obesity impairs the synthesis of β-F1-ATPase in muscle at the translational level, reducing the content of β-F1-ATPase in parallel with reduced capacity for ATP generation via the ATP synthase complex.

show abstract

“…We observed in NAFLD a significant correlation between plasma lumican FSR and hepatic collagen FSR, providing a potentially noninvasive approach to identify patients with active fibrotic disease. We recently reported a similar heavy water labeling–based “virtual biopsy” approach for measuring the FSR of skeletal muscle proteins from the turnover of muscle‐specific proteins that are found in blood (e.g., creatine kinase‐type M and carbonic anhydrase‐3) . Lumican, a proteoglycan involved in collagen fibril formation and the regulation of transforming growth factor‐β activity, is not a liver‐specific protein but has previously been shown to be overexpressed in hepatic tissue collected from patients with NASH .…”

Section: Discussionmentioning

confidence: 99%

Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood

Decaris

Emson

et al. 2016

Hepatology

Self Cite

View full text Add to dashboard Cite

Excess collagen synthesis (fibrogenesis) in the liver plays a causal role in the progression of nonalcoholic fatty liver disease (NAFLD). Methods are needed to identify patients with more rapidly progressing disease and to demonstrate early response to treatment. We describe here a novel method to quantify hepatic fibrogenesis flux rates both directly in liver tissue and noninvasively in blood. Twenty‐one patients with suspected NAFLD ingested heavy water (2H2O, 50‐mL aliquots) two to three times daily for 3‐5 weeks prior to a clinically indicated liver biopsy. Liver collagen fractional synthesis rate (FSR) and plasma lumican FSR were measured based on 2H labeling using tandem mass spectrometry. Patients were classified by histology for fibrosis stage (F0‐F4) and as having nonalcoholic fatty liver or nonalcoholic steatohepatitis (NASH). Magnetic resonance elastography measurements of liver stiffness were also performed. Hepatic collagen FSR in NAFLD increased with advancing disease stage (e.g., higher in NASH than nonalcoholic fatty liver, positive correlation with fibrosis score and liver stiffness) and correlated with hemoglobin A1C. In addition, plasma lumican FSR demonstrated a significant correlation with hepatic collagen FSR. Conclusion: Using a well‐characterized cohort of patients with biopsy‐proven NAFLD, this study demonstrates that hepatic scar in NASH is actively remodeled even in advanced fibrosis, a disease that is generally regarded as static and slowly progressive. Moreover, hepatic collagen FSR correlates with established risks for fibrotic disease progression in NASH, and plasma lumican FSR correlates with hepatic collagen FSR, suggesting applications as direct or surrogate markers, respectively, of hepatic fibrogenesis in humans. (Hepatology 2017;65:78‐88).

show abstract

Circulating protein synthesis rates reveal skeletal muscle proteome dynamics

Cited by 72 publications

References 69 publications

Dynamic proteome profiling of individual proteins in human skeletal muscle after a high‐fat diet and resistance exercise

Dynamic proteome profiling of individual proteins in human skeletal muscle after a high‐fat diet and resistance exercise

Mitochondrial ATP synthase β‐subunit production rate and ATP synthase specific activity are reduced in skeletal muscle of humans with obesity

Identifying nonalcoholic fatty liver disease patients with active fibrosis by measuring extracellular matrix remodeling rates in tissue and blood

Contact Info

Product

Resources

About