Lysosomal and proteasome-dependent proteolysis are differentially regulated by insulin and/or amino acids following feeding in young, mature and old rats

Capel, Frédéric; Prod'Homme, Magalie; Béchet, Daniel; Taillandier, Daniel; Balage, Michèle; Attaix, Didier; Combaret, Lydie

doi:10.1016/j.jnutbio.2008.05.017

Cited by 14 publications

(5 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data are consistent with the elevated rate of proteolysis observed in aged humans (87) and elevated rate of 3-methylhistidine excretion in rats (63). Although these data suggest sarcopenia may be due solely to an increase in proteolysis, as opposed to a decrease in protein synthesis, the assessment of protein metabolism was conducted in the postabsorptive state (ϳ3-5 h after removal of food), and aging has been shown to attenuate the anabolic response of muscle protein synthesis to nutrient stimulation (2,6). Hence, the relative importance of changes in protein synthesis and degradation as a cause for sarcopenia may vary depending on nutritional fluctuations.…”

Section: R892 Aging Alcohol and Muscle Protein Balancesupporting

confidence: 65%

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Korzick

Sharda

Pruznak

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

The present study sought to determine whether the protein catabolic response in skeletal muscle produced by chronic alcohol feeding was exaggerated in aged rats. Adult (3 mo) and aged (18 mo) female F344 rats were fed a nutritionally complete liquid diet containing alcohol (36% of total calories) or an isocaloric isonitrogenous control diet for 20 wk. Muscle (gastrocnemius) protein synthesis, as well as mTOR and proteasome activity did not differ between control-fed adult and aged rats, despite the increased TNF-α and IL-6 mRNA and decreased IGF-I mRNA in muscle of aged rats. Compared with alcohol-fed adult rats, aged rats demonstrated an exaggerated alcohol-induced reduction in lean body mass and protein synthesis (both sarcoplasmic and myofibrillar) in gastrocnemius. Alcohol-fed aged rats had enhanced dephosphorylation of 4E-BP1, as well as enhanced binding of raptor with both mTOR and Deptor, and a decreased binding of raptor with 4E-BP1. Alcohol feeding of both adult and aged rats reduced RagA binding to raptor. The LKB1-AMPK-REDD1 pathway was upregulated in gastrocnemius from alcohol-fed aged rats. These exaggerated alcohol-induced effects in aged rats were associated with a greater decrease in muscle but not circulating IGF-I, but no further increase in inflammatory mediators. In contrast, alcohol did not exaggerate the age-induced increase in atrogin-1 and MuRF1 mRNA or the increased proteasome activity. Our results demonstrate that, compared with adult rats, the gastrocnemius from aged rats is more sensitive to the catabolic effects of alcohol on protein synthesis, but not protein degradation, and this exaggerated response may be AMPK-dependent.

show abstract

Section: R892 Aging Alcohol and Muscle Protein Balancesupporting

confidence: 65%

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Korzick

Sharda

Pruznak

et al. 2013

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…With the use of proteomics, we previously reported in intestinal epithelial Caco-2 cells that glutamine affected 41%, 45%, and 8% of proteins involved in protein synthesis and degradation under control, apoptotic, or inflammatory conditions, respectively (43,44). Postprandial hyperaminoacidemia and hyperinsulinemia were associated with a fall of proteasome-dependent proteolysis in adult rat muscle (32) that appeared mainly related to insulin (45). In duodenal mucosa, chymotrypsin-like proteasome activity remained unaffected by an oral nutritional supplement compared with saline (4), whereas lysosomal cathepsin D activity was reduced.…”

Section: Discussionmentioning

confidence: 99%

Enteral delivery of proteins stimulates protein synthesis in human duodenal mucosa in the fed state through a mammalian target of rapamycin–independent pathway

Coëffier¹,

Claeyssens²,

Bôle‐Feysot³

et al. 2013

The American Journal of Clinical Nutrition

View full text Add to dashboard Cite

Background: Glutamine modulates duodenal protein metabolism in fasted healthy humans, but its effects in a fed state remain unknown. Objective: We aimed to assess the effects of either glutamine or an isonitrogenous protein mixture on duodenal protein metabolism in humans in the fed state. Design: Twenty-four healthy volunteers were randomly included in 2 groups. Each volunteer was studied on 2 occasions in a random order and received, during 5 h, either an enteral infusion of maltodextrins alone (0.25 g $ kg 21 $ h 21 ; both groups) that mimicked a carbohydrate fed state or maltodextrins with glutamine (group 1) or anSimultaneously, a continuous intravenous infusion of 13 C-leucine and 2 H 5 -phenylalanine (both 9 mmol $ kg 21 $ h 21 ) was performed.Endoscopic duodenal biopsies were taken. Leucine and phenylalanine enrichments were assessed by using gas chromatography-mass spectrometry in duodenal proteins and the intracellular free amino acids pool to calculate the mucosal fractional synthesis rate (FSR). Proteasome proteolytic activities and phosphokinase expression were assessed by using specific fluorogenic substrates and macroarrays, respectively. Results: The FSR and proteasome activity were not different after the glutamine supply compared with after maltodextrins alone. In contrast, the FSR increased (1.7-fold increase; P , 0.05) after protein-powder delivery without modification of total proteasome activity. The protein powder increased insulinemia, PI3 kinase, and erk phosphorylation but did not affect the mammalian target of rapamycin (mTOR) pathway and mitogen-activated protein kinase signal-integrating kinase 1 phosphorylation. A trend for an increase of eukaryotic translation initiation factor 4E phosphorylation was observed (P = 0.07). Conclusion: In the carbohydrate fed state, enteral proteins but not glutamine increased duodenal protein synthesis through an mTOR independent pathway in humans. This trial was registered at clinicaltrials.gov as NCT01254110. Am J Clin Nutr 2013;97:286-94.

show abstract

“…This could be explained by the fact that protein consumption in the HP-R group was nearly 3-fold that of the OI-R group, and 2-fold that of the OI rats, and was in line with the down-regulation of proteolysis pathways by amino acids in muscle. 46,47 To our knowledge, no data are available on the kidney and energy restriction; further studies are needed to understand the biological significance of an increase in proteolysis markers in this organ and to confirm these observations by flux measurements.…”

mentioning

confidence: 99%

Energy restriction only slightly influences protein metabolism in obese rats, whatever the level of protein and its source in the diet

et al. 2012

View full text Add to dashboard Cite

BACKGROUND: High protein (HP) diets during energy restriction have been studied extensively regarding their ability to reduce body fat and preserve lean body mass, but little is known about their effects on protein metabolism in lean tissues. OBJECTIVE: To determine the effects of energy restriction and protein intake on protein anabolism and catabolism in rats. METHODS: For 5 weeks, 56 male Wistar rats were fed an obesity induction (OI) diet . They were then subjected to a 40% energy restriction using the OI diet or a balanced HP diet for 3 weeks, whereas a control group was fed the OI diet ad libitum (n ¼ 8 per group). HP-restricted rats were divided into five groups differing only in terms of their protein source: total milk proteins, casein (C), whey (W), a mix of 50% C and W, and soy (n ¼ 8). The animals were then killed in the postprandial state and their body composition was determined. Protein synthesis rates were determined in the liver, gastrocnemius and kidney using a subcutaneous 13 C valine flooding dose. mRNA levels were measured for key enzymes involved in the three proteolysis pathways. RESULTS: Energy restriction, but not diet composition, impacted weight loss and adiposity, whereas lean tissue mass (except in the kidney) was not influenced by diet composition. Levels of neoglucogenic amino acids tended to fall under energy restriction (Po0.06) but this was reversed by a high level of protein. The postprandial protein synthesis rates in different organs were similar in all groups. By contrast, mRNA levels encoding proteolytic enzymes rose under energy restriction in the muscle and kidney, but this was counteracted by a HP level. CONCLUSIONS: In adult obese rats, energy restriction but not diet composition affected fat pads and had little impact on protein metabolism, despite marked effects on proteolysis in the kidney and muscle.

show abstract

Lysosomal and proteasome-dependent proteolysis are differentially regulated by insulin and/or amino acids following feeding in young, mature and old rats

Cited by 14 publications

References 27 publications

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Aging accentuates alcohol-induced decrease in protein synthesis in gastrocnemius

Enteral delivery of proteins stimulates protein synthesis in human duodenal mucosa in the fed state through a mammalian target of rapamycin–independent pathway

Energy restriction only slightly influences protein metabolism in obese rats, whatever the level of protein and its source in the diet

Contact Info

Product

Resources

About