Active involvement of PKC for insulin-mediated rates of muscle protein synthesis in Zucker rats

Fluckey, James D.; Cortright, Ronald N.; Tapscott, Edward B.; Koves, Timothy R.; Smith, Latasha; Pohnert, Steven C.; Dohm, G. Lynis

doi:10.1152/ajpendo.00155.2003

Cited by 9 publications

(10 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Hyperaminoacidemia and elevated plasma Leu have been linked to increased mTOR activity [10], [22], [23] and PKC pathway activation [71], [72]. These pathways have been linked to activation of protein synthesis consistent with our observations in obese rats.…”

Section: Discussionsupporting

confidence: 89%

Leucine and Protein Metabolism in Obese Zucker Rats

et al. 2013

View full text Add to dashboard Cite

Branched-chain amino acids (BCAAs) are circulating nutrient signals for protein accretion, however, they increase in obesity and elevations appear to be prognostic of diabetes. To understand the mechanisms whereby obesity affects BCAAs and protein metabolism, we employed metabolomics and measured rates of [1-14C]-leucine metabolism, tissue-specific protein synthesis and branched-chain keto-acid (BCKA) dehydrogenase complex (BCKDC) activities. Male obese Zucker rats (11-weeks old) had increased body weight (BW, 53%), liver (107%) and fat (∼300%), but lower plantaris and gastrocnemius masses (−21–24%). Plasma BCAAs and BCKAs were elevated 45–69% and ∼100%, respectively, in obese rats. Processes facilitating these rises appeared to include increased dietary intake (23%), leucine (Leu) turnover and proteolysis [35% per g fat free mass (FFM), urinary markers of proteolysis: 3-methylhistidine (183%) and 4-hydroxyproline (766%)] and decreased BCKDC per g kidney, heart, gastrocnemius and liver (−47–66%). A process disposing of circulating BCAAs, protein synthesis, was increased 23–29% by obesity in whole-body (FFM corrected), gastrocnemius and liver. Despite the observed decreases in BCKDC activities per gm tissue, rates of whole-body Leu oxidation in obese rats were 22% and 59% higher normalized to BW and FFM, respectively. Consistently, urinary concentrations of eight BCAA catabolism-derived acylcarnitines were also elevated. The unexpected increase in BCAA oxidation may be due to a substrate effect in liver. Supporting this idea, BCKAs were elevated more in liver (193–418%) than plasma or muscle, and per g losses of hepatic BCKDC activities were completely offset by increased liver mass, in contrast to other tissues. In summary, our results indicate that plasma BCKAs may represent a more sensitive metabolic signature for obesity than BCAAs. Processes supporting elevated BCAA]BCKAs in the obese Zucker rat include increased dietary intake, Leu and protein turnover along with impaired BCKDC activity. Elevated BCAAs/BCKAs may contribute to observed elevations in protein synthesis and BCAA oxidation.

show abstract

Section: Discussionsupporting

confidence: 89%

Leucine and Protein Metabolism in Obese Zucker Rats

et al. 2013

View full text Add to dashboard Cite

show abstract

“…As such, an important goal of our study was to elucidate whether insulin resistance syndrome is associated with a uniform perturbation in FSR or whether specific subfractions are preferentially affected over others depending upon biological function [e.g., substrate metabolism (cytosol/mitochondria) vs. contractile activity (myofibrils)]. Although the results generally corroborate earlier work that assessed protein synthesis in this rat strain (18,24,53), we have extended previous observations by demonstrating that the suppression is significantly less than reported previously (in younger rats) and isolated to subfractions involved in contractile function rather than substrate metabolism. Our findings are consistent with those of Fluckey et al (25), who showed an augmentation in mixed muscle protein synthesis rates in 3-mo-old obese rats in situ, and those of Bell et al (5), who reported an increased protein turnover in type 2 diabetic humans.…”

Section: Insulin Resistance Syndrome Does Not Impair Synthesis Rates supporting

confidence: 84%

Insulin resistance syndrome blunts the mitochondrial anabolic response following resistance exercise

Nilsson

Greene

Dobson

et al. 2010

American Journal of Physiology-Endocrinology and Metabolism

Self Cite

View full text Add to dashboard Cite

Metabolic risk factors associated with insulin resistance syndrome may attenuate augmentations in skeletal muscle protein anabolism following contractile activity. The purpose of this study was to investigate whether or not the anabolic response, as defined by an increase in cumulative fractional protein synthesis rates (24-h FSR) following resistance exercise (RE), is blunted in skeletal muscle of a well-established rodent model of insulin resistance syndrome. Four-month-old lean ( Fa/?) and obese ( fa/fa) Zucker rats engaged in four lower body RE sessions over 8 days, with the last bout occurring 16 h prior to muscle harvest. A priming dose of deuterium oxide (2H2O) and 2H2O-enriched drinking water were administered 24 h prior to euthanization for assessment of cumulative FSR. Fractional synthesis rates of mixed (−5%), mitochondrial (−1%), and cytosolic (+15%), but not myofibrillar, proteins (−16%, P = 0.012) were normal or elevated in gastrocnemius muscle of unexercised obese rats. No statistical differences were found in the anabolic response of cytosolic and myofibrillar subfractions between phenotypes, but obese rats were not able to augment 24-h FSR of mitochondria to the same extent as lean rats following RE (+14% vs. +28%, respectively). We conclude that the mature obese Zucker rat exhibits a mild, myofibrillar-specific suppression in basal FSR and a blunted mitochondrial response to contractile activity in mixed gastrocnemius muscle. These findings underscore the importance of assessing synthesis rates of specific myocellular subfractions to fully elucidate perturbations in basal protein turnover rates and differential adaptations to exercise stimuli in metabolic disease.

show abstract

“…G-CSF activates PKC in many myeloid cell lines [10] and PKCs can increase protein synthesis in rodent skeletal muscle [15]. G-CSF down regulates calmodulin dependant kinases (CaMK), specifically CaMK IV in a myelodysplastic cell line [31].…”

Section: Discussionmentioning

confidence: 99%