Muscle Protein Metabolism during Compensatory Growth with Changing Dietary Lysine Levels from Deficient to Sufficient in Growing Rats

Abstract

Summary Livestock and laboratory animals show compensatory growth when they are fed ad libitum following a period of restriction feeding. Lysine is a major limiting essential amino acid in the diets both for humans and animals. We hypothesized that changing dietary lysine levels from deficient to sufficient induced compensatory growth in young rats. We elucidated the effect of lysine sufficiency on the dynamics of hormones, relevant to muscle protein synthesis and degradation, insulin-like growth factor-I (IGF-I) and corticosterone, and on the expression of proteolytic-related genes in skeletal muscle during compensatory growth. Lysine sufficiency where the dietary lysine level was increased from 0.46% to 1.30% after 2 wk of subjecting the rats to the lower lysine level induced 80% enhancement of growth rate of rats. During compensatory growth with the lysine sufficiency, fractional muscle protein synthesis rates were higher whereas fractional muscle protein degradation rates were lower than those of the control group ( p Ͻ 0.05). After lysine sufficiency, the expression of atrogin-1/MAFbx mRNA was decreased in gastrocnemius muscle ( p Ͻ 0.05). With the lysine sufficiency, serum IGF-I concentration increased ( p Ͻ 0.05) whereas serum corticosterone decreased ( p Ͻ 0.05). These findings suggest that compensatory growth with lysine sufficiency is due to a change of hormone levels before and after changing diets, resulting in incrementation of protein synthesis and suppression of protein degradation of skeletal muscle. Key Words compensatory growth, lysine, rat, IGF-I, corticosteroneOne of the important subjects in nutritional science is to elucidate how humans and animals respond and adapt to transitions of nutritional status and changes of metabolic reaction that occur during the adaptation.There are numerous reports about adaptation of animals to excess or deficiency of nutrients or energy in diets. Compensatory growth is an example of adaptation to nutritional status. Livestock and laboratory animals show compensatory growth when they are fed ad libitum following a period of restricted feeding or fed adequate energy following a period of energy restriction ( 1-3 ). Previous studies in rats and pigs showed that when animals that had been fed a protein-free or a low protein diet were refed a diet containing a sufficient amount of protein, they developed faster than animals fed a control diet particularly for the first few days after the diet replacement ( 4-6 ). Promoted protein accumulation during compensatory growth is due to a larger difference between the rate of muscle protein synthesis and the rate of muscle protein degradation compared to normal growth. The phenomenon has been considered a transitional state in adapting to the nutritional status. Both anabolic and catabolic hormones may be involved in this response. All of these previous studies indicate that sufficiency of dietary protein and amino acid levels plays a role as a trigger for compensatory growth in animals. However, these studies provide no ...

A Systems Biology Approach Using Transcriptomic Data Reveals Genes and Pathways in Porcine Skeletal Muscle Affected by Dietary Lysine

“…That the expression levels of the genes related to protein ubiquitination pathway were downregulated with the increased level of dietary lysine implies that a high level of dietary lysine may suppress protein degradation and that dietary lysine deficiency may stimulate protein degradation through the ubiquitin-proteasome degradation pathway. This implication is supported by an in vivo study [22], which showed that dietary lysine supplementation inhibited the ubiquitin-proteasome pathway in the skeletal muscle of rats.…”

Regulation of Skeletal Muscle Protein Degradation and Synthesis by Oral Administration of Lysine in Rats

“…The autophagic-lysosomal pathway may be a particularly important proteolytic pathway with regard to the inhibitory effects on amino acids, although Hamel et al (33) reported that Lys directly inhibited the activity of proteasome prepared from rat muscle in vitro. Ishida et al (18) suggested that dietary Lys decreased the fractional protein degradation rate in skeletal muscle in growing rats using urinary MeHis excretion, and they confirmed the suppression of atrogin-1 mRNA expression in the skeletal muscle of rats fed sufficient Lys. Thus, dietary Lys may suppress both the autophagic-lysosomal pathway and the ubiquitin-proteasomal pathway.…”

“…Animals fed low Lys diets grow more slowly than those fed standard diets (17,18). Therefore, addition of Lys to low-Lys diets is considered to be essential for maturity in growing animals.…”

Dietary L-Lysine Prevents Arterial Calcification in Adenine-Induced Uremic Rats

“…47 Our findings agreed with those of a study of Ishida et al, in which they demonstrated that dietary L-Lys downregulates E3 ubiquitin ligase atrogin-1 (also known as muscle atrophy F-box), a key enzyme for muscle degradation. 48 Fourth, the similar plasma Glu levels among the three adenine-loaded groups might be attributed to proximal tubular damage by adenine. The proximal tubule is the major expression site of glutaminase, a key enzyme that generates Glu+NH 4 + from Gln.…”