Caloric restriction optimizes the proteasome pathway with aging in rat plantaris muscle: implications for sarcopenia

Hepple, Russell T.; Qin, Maggie; Nakamoto, Hideko; Goto, Sataro

doi:10.1152/ajpregu.90478.2008

Cited by 70 publications

(56 citation statements)

References 52 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data were consistent with the results of many other studies have demonstrated that insulin-mediated glucose uptake by skeletal muscle is also greater for CR compared with AL rats (8,17,42,56). The results with isolated muscles are also consistent with the results of previous studies that have measured whole body insulin sensitivity in adult CR versus AL rats by various methods, including glucose infusion rate during a euglycemichyperinsulinemic clamp (23,33).…”

Section: R132 Calorie Restriction and Mapk Signaling In Skeletal Musclesupporting

confidence: 91%

Improved insulin sensitivity with calorie restriction does not require reduced JNK1/2, p38, or ERK1/2 phosphorylation in skeletal muscle of 9-month-old rats

Sharma¹,

Bhat²,

Kassa³

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

Sharma N, Bhat AD, Kassa AD, Xiao Y, Arias EB, Cartee GD. Improved insulin sensitivity with calorie restriction does not require reduced JNK1/2, p38, or ERK1/2 phosphorylation in skeletal muscle of 9-month-old rats. Am J Physiol Regul Integr Comp Physiol 302: R126 -R136, 2012. First published October 19, 2011 doi:10.1152/ajpregu.00372.2011.-Calorie restriction [CR; ϳ40% below ad libitum (AL) intake] improves the health of many species, including rats, by mechanisms that may be partly related to enhanced insulin sensitivity for glucose disposal by skeletal muscle. Excessive activation of several mitogen-activated protein kinases (MAPKs), including JNK1/2, p38, and ERK1/2 has been linked to insulin resistance. Although insulin can activate ERK1/2, this effect is not required for insulin-mediated glucose uptake. We hypothesized that skeletal muscle from male 9-mo-old Fischer 344/Brown Norway rats CR (35-40% beginning at 3 mo old) versus AL rats would have 1) attenuated activation of JNK1/2, p38, and ERK1/2 under basal conditions; and 2) no difference for insulin-induced ERK1/2 activation. In contrast to our hypothesis, there were significant CR-related increases in the phosphorylation of p38 (epitrochlearis, soleus, and gastrocnemius), JNK1 (epitrochlearis and soleus), and JNK2 (gastrocnemius). Consistent with our hypothesis, CR did not alter insulin-mediated ERK1/2 activation. The greater JNK1/2 and p38 phosphorylation with CR was not attributable to diet effects on muscle oxidative stress (assessed by protein carbonyls and 4-hydroxynonenal protein conjugates). In muscles from the same rats used for the present study, we previously reported a CR-related increase in insulin-mediated glucose uptake by the epitrochlearis and the soleus (Sharma N, Arias EB, Bhat AD, Sequea DA, Ho S, Croff KK, Sajan MP, Farese RV, Cartee GD. Am J Physiol Endocrinol Metab 300: E966 -E978, 2011). The present results indicate that the improved insulin sensitivity with CR is not attributable to attenuated MAPK phosphorylation in skeletal muscle.

show abstract

Section: R132 Calorie Restriction and Mapk Signaling In Skeletal Musclesupporting

confidence: 91%

Improved insulin sensitivity with calorie restriction does not require reduced JNK1/2, p38, or ERK1/2 phosphorylation in skeletal muscle of 9-month-old rats

Sharma¹,

Bhat²,

Kassa³

et al. 2012

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…4 and 5). Elevated 20S proteasome levels were previously reported in muscles from aged F344/BN and LOU rats (17)(18)(19)55), but Ferrington and co-workers (18,55) found the expression of the 19S (PA700) unchanged. However, in those studies proteasomes were measured after ultracentrifugation in a buffer lacking ATP, which is necessary to maintain the structural integrity of the 26S.…”

Section: Discussionmentioning

confidence: 82%

Muscle Wasting in Aged, Sarcopenic Rats Is Associated with Enhanced Activity of the Ubiquitin Proteasome Pathway

Altun

Besche

Overkleeft

et al. 2010

Journal of Biological Chemistry

197

155

View full text Add to dashboard Cite

Among the hallmarks of aged organisms are an accumulation of misfolded proteins and a reduction in skeletal muscle mass ("sarcopenia"). We have examined the effects of aging and dietary restriction (which retards many age-related changes) on components of the ubiquitin proteasome system (UPS) in muscle. The hindlimb muscles of aged (30 months old) rats showed a marked loss of muscle mass and contained 2-3-fold higher levels of 26S proteasomes than those of adult (4 months old) controls. 26S proteasomes purified from muscles of aged and adult rats showed a similar capacity to degrade peptides, proteins, and an ubiquitylated substrate, but differed in levels of proteasome-associated proteins (e.g. the ubiquitin ligase E6AP and deubiquitylating enzyme USP14). Also, the activities of many other deubiquitylating enzymes were greatly enhanced in the aged muscles. Nevertheless, their content of polyubiquitylated proteins was higher than in adult animals. The aged muscles contained higher levels of the ubiquitin ligase CHIP, involved in eliminating misfolded proteins, and MuRF1, which ubiquitylates myofibrillar proteins. These muscles differed from ones rapidly atrophying due to disease, fasting, or disuse in that Atrogin-1/MAFbx expression was low and not inducible by glucocorticoids. Thus, the muscles of aged rats showed many adaptations indicating enhanced proteolysis by the UPS, which may enhance their capacity to eliminate misfolded proteins and seems to contribute to the sarcopenia. Accordingly, dietary restriction decreased or prevented the aging-associated increases in proteasomes and other UPS components and reduced muscle wasting.

show abstract

“…19 In the muscle, variable results have been reported, depending on the muscle, age and model (rat, monkey). 42 --44 Hepple et al 42 showed that proteosome activity in muscle during caloric restriction decreased in line with muscle mass, but Chambon --Savanovitch et al 45 did not report any effect of energy restriction on 3-metylhistidine excretion in old rats. During our study, energy restriction did not cause any loss of muscle mass, and the lack of any effect on the mRNA-encoding key enzymes involved in proteolysis pathways (at least the proteasome pathway) was consistent with the observations made by Hepple et al 42 By contrast, we determined a marked effect of the protein level on the muscle gene expression of these enzymes, whatever the pathway.…”

mentioning

confidence: 99%

“…42 --44 Hepple et al 42 showed that proteosome activity in muscle during caloric restriction decreased in line with muscle mass, but Chambon --Savanovitch et al 45 did not report any effect of energy restriction on 3-metylhistidine excretion in old rats. During our study, energy restriction did not cause any loss of muscle mass, and the lack of any effect on the mRNA-encoding key enzymes involved in proteolysis pathways (at least the proteasome pathway) was consistent with the observations made by Hepple et al 42 By contrast, we determined a marked effect of the protein level on the muscle gene expression of these enzymes, whatever the pathway. 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.…”

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

Caloric restriction optimizes the proteasome pathway with aging in rat plantaris muscle: implications for sarcopenia

Cited by 70 publications

References 52 publications

Improved insulin sensitivity with calorie restriction does not require reduced JNK1/2, p38, or ERK1/2 phosphorylation in skeletal muscle of 9-month-old rats

Improved insulin sensitivity with calorie restriction does not require reduced JNK1/2, p38, or ERK1/2 phosphorylation in skeletal muscle of 9-month-old rats

Muscle Wasting in Aged, Sarcopenic Rats Is Associated with Enhanced Activity of the Ubiquitin Proteasome 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