Tissue-specific effects of chronic dietary leucine and norleucine supplementation on protein synthesis in rats

Abstract

Acute administration of leucine and norleucine activates the mammalian target of rapamycin (mTOR) cell-signaling pathway and increases rates of protein synthesis in a number of tissues in fasted rats. Although persistent stimulation of mTOR signaling is thought to increase protein synthetic capacity, little information is available concerning the effects of chronic administration of these agonists on protein synthesis, mTOR signal transduction, or leucine metabolism. Hence, we developed a model of chronic leucine/norleucine supplementation via drinking water and examined the effects of chronic (12 days) supplementation on protein synthesis in adipose tissue, kidney, heart, liver, and skeletal muscle from ad libitum-fed rats. The relative concentration of proteins involved in mTOR signaling and the two initial steps in leucine oxidation were also examined. Leucine or norleucine supplementation was accompanied by increased rates of protein synthesis in adipose tissue, liver, and skeletal muscle, but not in heart or kidney. Supplementation was not associated with increases in the anabolic hormones insulin or insulin-like growth factor I. Chronic supplementation did not cause apparent adaptation in either components of the mTOR cell-signaling pathway that respond to leucine (mTOR, ribosomal protein S6 kinase, and eukaryotic initiation factor 4E-binding protein-1) or the first two steps in leucine metabolism (the mitochondrial isoform of branched-chain amino acid transaminase, branched-chain keto acid dehydrogenase, and branched-chain keto acid dehydrogenase kinase), which may be involved in terminating the signal from leucine. These results suggest that provision of leucine or norleucine supplementation via the drinking water results in stimulation of postprandial protein synthesis in adipose tissue, skeletal muscle, and liver without notable adaptive changes in signaling proteins or metabolic enzymes.

Excess Leucine Intake Induces Serine Dehydratase in Rat Liver

“…Of the BCAAs, leucine appears to be the specific effector in protein synthesis in several tissues, including skeletal muscle, liver, and adipose tissue. 7,8) In the present study, we found that excess intake of leucine induced SDH activity with increased amounts of SDH mRNA.…”

Somatotropin-induced protein anabolism in hindquarters and portal-drained viscera of growing pigs

“…The increase in amino acid utilization and protein synthesis in the HQ, but not in the PDV, was mediated largely by the regional increase in blood flow. Interestingly, recent studies have shown that adipose tissue protein synthesis is highly responsive to nutrient stimulation (31,32). Because ST induces a repartitioning of nutrients away from adipose tissue and toward lean tissue deposition (19), we postulate that the lack of ST-induced stimulation of whole body protein synthesis in the fed state may, in part, be due to an ST-induced suppression of the feeding-induced stimulation of protein synthesis in adipose tissue.…”

Protein synthesis regulation by leucine

“…protein synthesis, particularly by stimulating the activity of proteins involved in the translation process, which is critical for cells to control protein synthesis (Anthony et al, 2001;Lynch, Hutson, Patson, 2002a;Crozier et al, 2005;Garlick, 2005;. This modulation may involve the activation of specific intracellular pathways involved in protein synthesis, including activation of the mammalian target of rapamycin (mTOR) pathway.…”

“…Some of the benefits promoted by this diet on body composition can be attributed to high consumption of branched-chain aminoacids (BCAA), which include the aminoacids leucine, valine and isoleucine (Donato et al, 2004;Layman, Walker, 2006;Katsanos et al, 2006). According to this hypothesis, high protein consumption not only increases the availability of substrates (aminoacids) for protein synthesis, but also stimulates anabolic processes observed after high protein consumption (Campos et al, 1999).Leucine has been shown to modulate the rate ofprotein synthesis, particularly by stimulating the activity of proteins involved in the translation process, which is critical for cells to control protein synthesis (Anthony et al, 2001;Lynch, Hutson, Patson, 2002a;Crozier et al, 2005;Garlick, 2005;. This modulation may involve the activation of specific intracellular pathways involved in protein synthesis, including activation of the mammalian target of rapamycin (mTOR) pathway.…”