Presence of low-grade inflammation impaired postprandial stimulation of muscle protein synthesis in old rats

Aging is associated with a decline in skeletal muscle mass and function—termed sarcopenia—as mediated, in part, by muscle anabolic resistance. This metabolic phenomenon describes the impaired response of muscle protein synthesis (MPS) to the provision of dietary amino acids and practice of resistance-based exercise. Recent observations highlight the gut-muscle axis as a physiological target for combatting anabolic resistance and reducing risk of sarcopenia. Experimental studies, primarily conducted in animal models of aging, suggest a mechanistic link between the gut microbiota and muscle atrophy, mediated via the modulation of systemic amino acid availability and low-grade inflammation that are both physiological factors known to underpin anabolic resistance. Moreover, in vivo and in vitro studies demonstrate the action of specific gut bacteria (Lactobacillus and Bifidobacterium) to increase systemic amino acid availability and elicit an anti-inflammatory response in the intestinal lumen. Prospective lifestyle approaches that target the gut-muscle axis have recently been examined in the context of mitigating sarcopenia risk. These approaches include increasing dietary fiber intake that promotes the growth and development of gut bacteria, thus enhancing the production of short-chain fatty acids (SCFA) (acetate, propionate, and butyrate). Prebiotic/probiotic/symbiotic supplementation also generates SCFA and may mitigate low-grade inflammation in older adults via modulation of the gut microbiota. Preliminary evidence also highlights the role of exercise in increasing the production of SCFA. Accordingly, lifestyle approaches that combine diets rich in fiber and probiotic supplementation with exercise training may serve to produce SCFA and increase microbial diversity, and thus may target the gut-muscle axis in mitigating anabolic resistance in older adults. Future mechanistic studies are warranted to establish the direct physiological action of distinct gut microbiota phenotypes on amino acid utilization and the postprandial stimulation of muscle protein synthesis in older adults.

Download Full-text

The possible involvement of prostaglandin F2α in the stimulation of muscle protein synthesis by insulin

Biochemical and Biophysical Research Communications ◽

10.1016/s0006-291x(83)80253-8 ◽

1983 ◽

Vol 116 (3) ◽

pp. 1084-1090 ◽

Cited By ~ 35

Author(s):

P.J. Reeds ◽

R.M. Palmer

Keyword(s):

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Prostaglandin F2α ◽

Stimulation Of

Download Full-text

Role of insulin and IGF-I in activation of muscle protein synthesis after oral feeding

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1996.270.4.e614 ◽

1996 ◽

Vol 270 (4) ◽

pp. E614-E620 ◽

Cited By ~ 16

Author(s):

E. Svanberg ◽

H. Zachrisson ◽

C. Ohlsson ◽

B. M. Iresjo ◽

K. G. Lundholm

Keyword(s):

Protein Synthesis ◽

Skeletal Muscles ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Oral Feeding ◽

Myofibrillar Proteins ◽

Diabetic Mice ◽

Igf I ◽

Stimulation Of

The aim was to evaluate the role of insulin and insulin-like growth factor I (IGF-I) in activation of muscle protein synthesis after oral feeding. Synthesis rate of globular and myofibrillar proteins in muscle tissue was quantified by a flooding dose of radioactive phenylalanine. Muscle tissue expression of IGF-I mRNA was measured. Normal (C57 Bl) and diabetic mice (type I and type II) were subjected to an overnight fast (18 h) with subsequent refeeding procedures for 3 h with either oral chow intake or provision of insulin, IGF-I, glucose, and amino acids. Anti-insulin and anti-IGF-I were provided intraperitoneally before oral refeeding in some experiments. An overnight fast reduced synthesis of both globular (38 +/- 3%) and myofibrillar proteins (54 +/- 3%) in skeletal muscles, which was reversed by oral refeeding. Muscle protein synthesis, after starvation/ refeeding, was proportional and similar to changes in skeletal muscle IGF-I mRNA expression. Diabetic mice responded quantitatively similarly to starvation/refeeding in muscle protein synthesis compared with normal mice (C57 Bl). Both anti-insulin and anti-IGF-I attenuated significantly the stimulation of muscle protein synthesis in response to oral feeding, whereas exogenous provision of either insulin or IGF-I to overnight-starved and freely fed mice did not clearly stimulate protein synthesis in skeletal muscles. Our results support the suggestion that insulin and IGF-I either induce or facilitate the protein synthesis machinery in skeletal muscles rather than exerting a true stimulation of the biosynthetic process during feeding.

Download Full-text

Adaptation to prolonged starvation in the rat: curtailment of skeletal muscle proteolysis

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1981.241.4.e321 ◽

1981 ◽

Vol 241 (4) ◽

pp. E321-E327 ◽

Cited By ~ 10

Author(s):

M. N. Goodman ◽

M. A. McElaney ◽

N. B. Ruderman

Keyword(s):

Skeletal Muscle ◽

Protein Synthesis ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Early Event ◽

Body Protein ◽

Fed State ◽

Prolonged Starvation ◽

Obese Rats ◽

Old Rats

Previous studies have established that 16-wk-old nonobese and obese rats conserve body protein during prolonged starvation. To determine the basis for this, protein synthesis and degradation in skeletal muscle were evaluated in the isolated perfused hindquarters of these rats, in the fed state and when starved for 2, 5, 10, and 11 days. Rats aged 4 and 8 wk were used as a comparison. The results indicate that the response to starvation depends on several factors: the age of the rat, its degree of adiposity, and the duration of the fast. An early event in starvation was a decline in muscle protein synthesis. This occurred in all groups, albeit this reduction occurred more slowly in the older rats. A later response to starvation was an increase in muscle proteolysis. This occurred between 2 and 5 days in the 8-wk-old rats. In 16-wk-old rats it did not occur until between 5 and 10 days, and it was preceded by a period of decreased proteolysis. In 16-wk-old obese rats, a decrease in proteolysis persisted for upwards of 10 days and the secondary increase was not noted during the period of study. The data suggest that the ability of older and more obese rats to conserve body protein during starvation is due, in part, to a curtailment of muscle proteolysis. This adaptation seems to correlate with the availability of lipid fuels.

Download Full-text

Enhanced response of muscle protein synthesis and plasma insulin to food intake in suckled rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1993.265.2.r334 ◽

1993 ◽

Vol 265 (2) ◽

pp. R334-R340 ◽

Cited By ~ 28

Author(s):

T. A. Davis ◽

M. L. Fiorotto ◽

H. V. Nguyen ◽

P. J. Reeds

Keyword(s):

Protein Synthesis ◽

Food Intake ◽

Plasma Insulin ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Fed State ◽

Fasting And Refeeding ◽

Old Rats ◽

Amino Acid Concentrations

To compare the sensitivity of muscle protein synthesis to food intake in neonatal and weaned rats, 5- and 16-day-old suckled rats and 28-day-old weaned rats were either fed, fasted for 8-10 h, or refed for 1-4 h after an 8-h fast. Protein synthesis was measured in vivo in soleus and plantaris muscles with a large dose of L-[4-3H]phenylalanine. In fed rats, fractional rates of protein synthesis (KS) decreased with age. Fasting decreased KS, and refeeding increased KS most in 5-day-old animals, less in 16-day-old rats, and least in 28-day-old rats. In 5-day-old rats, there were no differences in KS between soleus and plantaris muscles in the fed state and after fasting and refeeding; at 28 days, KS was higher in soleus than in plantaris in fed rats, and the soleus did not respond to fasting and refeeding. In rats at all three ages, the concentration of most plasma amino acids decreased during fasting; when 5-day-old rats were refed, plasma amino acid concentrations increased, but not to the levels in the fed state. Plasma insulin concentrations increased with age. Plasma insulin concentrations decreased more rapidly with fasting and increased more extensively with refeeding in 5-day-old rats than in older rats. These results suggest that muscle protein synthesis is more responsive to food intake in young suckled rats than in older suckled or weaned rats; this increased responsiveness is accompanied by greater changes in circulating insulin concentrations.

Download Full-text

Stimulation of Muscle Protein Synthesis by Prolonged Parenteral Infusion of Leucine Is Dependent on Amino Acid Availability in Neonatal Pigs

Journal of Nutrition ◽

10.3945/jn.109.113621 ◽

2009 ◽

Vol 140 (2) ◽

pp. 264-270 ◽

Cited By ~ 52

Author(s):

Fiona A. Wilson ◽

Agus Suryawan ◽

Maria C. Gazzaneo ◽

Renán A. Orellana ◽

Hanh V. Nguyen ◽

...

Keyword(s):

Protein Synthesis ◽

Amino Acid ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Neonatal Pigs ◽

Amino Acid Availability ◽

Stimulation Of

Download Full-text

Glucocorticoid effects on insulin- and IGF-I-regulated muscle protein metabolism during aging

Journal of Endocrinology ◽

10.1677/joe.0.1560083 ◽

1998 ◽

Vol 156 (1) ◽

pp. 83-89 ◽

Cited By ~ 50

Author(s):

D Dardevet ◽

C Sornet ◽

I Savary ◽

E Debras ◽

P Patureau-Mirand ◽

...

Keyword(s):

Protein Synthesis ◽

Muscle Atrophy ◽

Protein Metabolism ◽

Muscle Protein ◽

Muscle Protein Synthesis ◽

Recovery Period ◽

Adult Rats ◽

Igf I ◽

Muscle Protein Metabolism ◽

Old Rats

This study was performed to assess the effect of glucocorticoids (dexamethasone) on insulin- and IGF-I-regulated muscle protein metabolism in adult and old rats. Muscle atrophy occurred more rapidly in old rats, and recovery of muscle mass was impaired when compared with adults. Muscle wasting resulted mainly from increased protein breakdown in adult rat but from depressed protein synthesis in the aged animal. Glucocorticoid treatment significantly decreased the stimulatory effect of insulin and IGF-I on muscle protein synthesis in adult rats by 25.9 and 58.1% respectively. In old rats, this effect was even greater, being 49.3 and 100% respectively. With regard to muscle proteolysis, glucocorticoids blunted the anti-proteolytic action of insulin and IGF-I in both age groups. During the recovery period, adult rats reversed the glucocorticoid-induced resistance of muscle protein metabolism within 3 days, at which time old rats still exhibited the decrease in insulin-regulated proteolysis. In conclusion, the higher sensitivity of old rat muscle to glucocorticoids may in part result from the greater modification of the effects of insulin and IGF-I on muscle protein metabolism. These responses to glucocorticoids in old rats may be associated with the emergence of muscle atrophy with advancing age.

Download Full-text