LAT2
Linker for activation of T-cells family member 2 (Linker for activation of B-cells) (Membrane-associated adapter molecule) (Non-T-cell activation linker) (Williams-Beuren syndrome chromosomal region 15 protein) (Williams-Beuren syndrome chromosomal region 5 protein) [LAB] [NTAL] [WBS15] [WBSCR15] [WBSCR5] [HSPC046]
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Birthweight and age can play a role in adaptational changes in plasma levels of glucose and amino acids by regulating the intestinal expression of specific nutrients transporters in piglets. The aim of the present study was to compare hematological features, circulating levels of glucose and amino acids, and small intestinal gene expression for transporters for glucose (SGLT1, GLUT2), amino acids (LAT2, b AT) and peptides (PepT1) between low birthweight (LBW) and normal birthweight (NBW) piglets at birth prior to suckling and day 7 after birth. A secondary aim was to evaluate correlations between circulating levels of glucose or amino acids and their transporters. There were significant age-dependent changes in the immune cell repertoire in the circulating blood (P<0.004). Blood glucose levels were lower in LBW piglets than in NBW piglets (P<0.05); in both birthweight groups, blood glucose increased with age. Plasma concentrations of histidine, isoleucine, proline and tryptophan showed significant changes with age (P<0.003). With regard to mRNA levels for the nutrient transporters, there were no differences between the two birthweight groups or between the two age groups. At day 7 postpartum, intestinal expression of SGLT1 or GLUT2 mRNA did not correlate with blood glucose level. Expression of LAT2 mRNA in the ileum correlated positively with plasma level of methionine (r=0.92, P<0.001). This is the first detailed analysis of hematological features, plasma glucose and amino acid levels, and nutrient transporter expression in LBW and NBW piglets during the early suckling period.
MeSH Terms
- Aging
- Amino Acids
- Animals
- Animals, Suckling
- Birth Weight
- Blood Glucose
- Intestine, Small
- Membrane Transport Proteins
- Swine
Keywords
- Amino acid transporters
- Glucose transporters
- Intestinal adaptation
- Low birthweight
- Normal birthweight
- Small intestine
Skeletal muscle (SM) is the most abundant tissue and the largest reservoir of protein in the body. It transports glucose in an insulin dependent manner by the glucose transporter type 4 (GLUT4) and contributes in the maintenance of serum amino acids concentration. By its mass and energetic requirements, it is fundamental for the systemic metabolic balance. In the present work, we present the effect of gestational undernourishment (GU) on the mechanical and metabolic properties of SM at birth and in old age in an animal model. Mechanical studies were performed on isolated muscles, while the GLUT4, amino acid transporters LAT2, SNAT2 and insulin receptors (IR) determination were performed on isolated transverse-tubule membranes (TT). The GU in offspring at birth, results in low muscle mass with increased contraction force and resistance to fatigue. However, in two-years old rats, there was muscle hypotrophy and sarcopenia, the force decreased between 50 and 70% in control rats and rats with GU respectively, accompanied by a lower expression of LAT2, SNAT2 and IR in TT. In conclusion, GU irreversibly affects the SM, an effect that could be similar in humans, which help us to understand the events that associate the GU with the metabolic debacle of SM and the metabolic diseases of human adulthood.
MeSH Terms
- Age Factors
- Amino Acid Transport System A
- Amino Acid Transport System y
- Amino Acid Transport Systems
- Amino Acids
- Animals
- Female
- Fusion Regulatory Protein 1, Light Chains
- Glucose
- Glucose Transporter Type 4
- Humans
- Malnutrition
- Models, Animal
- Muscle Contraction
- Muscle Strength
- Muscle, Skeletal
- Muscular Atrophy
- Pregnancy
- Prenatal Exposure Delayed Effects
- Rats
- Receptor, Insulin
- Sarcopenia
Keywords
- Aging
- Gestational undernourishment
- Glucose transporter type 4
- Skeletal muscle
Sarcopenia, the progressive decline in skeletal muscle mass and function with age, is a debilitating condition. It leads to inactivity, falls, and loss of independence. Despite this, its cause(s) and the underlying mechanism(s) are still poorly understood. In this study, small skeletal muscle fibre bundles isolated from the extensor digitorum longus (a fast-twitch muscle) and the soleus (a slow-twitch muscle) of adult mice of different ages (range 100-900 days old) were used to investigate the effects of ageing and dihydrotestosterone (DHT) treatment on protein synthesis as well as the expression and function of two amino acid transporters; the sodium-coupled neutral amino acid transporter (SNAT) 2, and the sodium-independent L-type amino-acid transporter (LAT) 2. At all ages investigated, protein synthesis was always higher in the slow-twitch than in the fast-twitch muscle fibres and decreased with age in both fibre types. However, the decline was greater in the fast-twitch than in the slow-twitch fibres and was accompanied by a reduction in the expression of SNAT2 and LAT2 at the protein level. Again, the decrease in the expression of the amino acid transporters was greater in the fast-twitch than in the slow-twitch fibres. In contrast, ageing had no effect on SNAT2 and LAT2 expressions at the mRNA level. Treating the muscle fibre bundles with physiological concentrations (~2 nM) of DHT for 1 h completely reversed the effects of ageing on protein synthesis and the expression of SNAT2 and LAT2 protein in both fibre types. From the observations that ageing is accompanied by a reduction in protein synthesis and transporter expression and that these effects are reversed by DHT treatment, we conclude that sarcopenia arises from an age-dependent reduction in protein synthesis caused, in part, by the lack of or by the low bioavailability of the male sex steroid, DHT.
MeSH Terms
- Aging
- Amino Acid Transport System A
- Amino Acid Transport System y
- Animals
- Dihydrotestosterone
- Female
- Fusion Regulatory Protein 1, Light Chains
- Mice, Inbred C57BL
- Muscle Fibers, Skeletal
- Protein Biosynthesis
- Sarcopenia
Keywords
- Ageing
- Amino acid transporters
- Protein synthesis
- Sarcopenia
- Skeletal muscle