Leucine and citrulline modulate muscle function in malnourished aged rats.

Protein energy malnutrition in the elderly causes preferential loss of muscle mass which is associated with poor functional states. Leucine and citrulline are able to stimulate muscle protein synthesis in aged rats but no study has been undertaken to evaluate their effect on muscle function. Sprague-Dawley male rats aged 23 months were used in the experiment. Part of them were subjected to a dietary restriction for 12 weeks and then assigned to four groups: a group was euthanized (restricted group), and the others were refed for 1 week with either a leucine-, a citrulline-supplemented diet, or a standard diet. The other rats were fed ad libitum. Muscle mass and motor activity significantly increased during the refeeding with either leucine or citrulline (respectively, +51 and +37% for muscle mass, P < 0.05). The improvement of muscle mass and of motor activity induced by leucine and citrulline was highly associated with that of maximal tetanic isometric force (r = 0.769, P < 0.0001; r = 0.389, P < 0.05, respectively) but only leucine improved maximal tetanic isometric force (+101%, P < 0.05). In conclusion, this is the first study to demonstrate the ability of two amino acids (leucine and citrulline) to modulate muscle function.

Ornithine alpha-ketoglutarate supplementation influences motor activity in healthy rats.

BACKGROUND: Ornithine alpha-ketoglutarate (OKG) improves nutritional status in malnourished patients. Published and unpublished data suggest OKG may have effects on the central nervous system that may contribute to its action. OBJECTIVE: We investigated the effect of an OKG-enriched diet on behaviour in healthy rats. DESIGN: Thirty male Wistar rats were randomised in three groups: the OKG group was fed for 5 days (D0-D5) at 90% of spontaneous food intake with an OKG-enriched diet (5 g/kg/d). The non-essential amino acids (NEAA) group was fed similarly with a regimen enriched with NEAA (glycine, alanine, histidine and serine) to be isonitrogenous to OKG group. The ad libitum (AL) group had no treatment and was fed ad libitum with a standard regimen throughout. Rats were tested at D4 for motor activity by actimetry, and at D5 first for spontaneous alternation behaviour measured in the Y-maze, and then for exploratory behaviour measured using the open-field test (stressful environment). RESULTS: We found that OKG supplementation enhanced global motricity by actimetry (AL 772 +/- 55, NEAA 811 +/- 54 vs. OKG 966 +/- 24 arbitrary units, P < 0.05) and total numbers of arms visited in the Y-maze (AL 26 +/- 2, NEAA 30 +/- 3 vs. OKG 38 +/- 3, P < 0.05). The lack of any effect of the OKG-enriched diet in the open-field test shows that the enhancement of locomotion activity was most probably not due to an increase in anxiety or fear in the rats. CONCLUSION: An OKG-enriched diet can induce beneficial stimulant effects that may be involved in the mechanism of action of OKG.

Alpha-lactalbumin-enriched diets enhance serotonin release and induce anxiolytic and rewarding effects in the rat.

Among food proteins, alpha-lactalbumin (LAC) has the highest ratio of tryptophan (Trp) over its competitor amino acids. Consequently, contrary to casein (CAS), LAC ingestion increases Trp access to the brain leading to enhanced serotonin (5-HT) synthesis. As an index of serotonergic activity, we assessed extracellular 5-HT in response to LAC ingestion, using microdialysis, and performed behavioural tests in rats in order to characterise the suggested improvements of mood observed in humans after ingestion of this protein. Rats were fed with diets enriched either in LAC or CAS as control, acutely (30 min meals) or chronically (3 and 6 days). A 30 min LAC meal significantly increased 5-HT release in the medial hypothalamus. This effect disappeared after 3 and 6 days of diet. The basal premeal 5-HT levels were increasingly enhanced by the LAC diet. Compared to a CAS meal, LAC increased the percentage of time spent on the open arms of the elevated plus maze and the number of visits to the centre of the open field, suggesting an anxiolytic-like effect. A single LAC meal decreased sucrose consumption, while 3 or 6 days diets enhanced it, reflecting an appetitive and/or rewarding action. In conclusion, LAC ingestion induces anxiolytic-like and rewarding effects possibly related to serotonergic activation. Shifting transiently, the commonly consumed CAS-enriched to LAC-enriched diets may induce beneficial effects on mood.

Behavioral responses to ingestion of different sources of fat. Involvement of serotonin?

In previous experiments, we described a decrease in extracellular hypothalamic serotonin, 5-hydroxy-tryptamine (5-HT), in response to ingestion of a lard meal. This effect was related to the low satiating potency of lard as compared with other nutrients. Since the composition in fatty acids might be important for these effects, the purpose of this study was to analyze the neurochemical and behavioral responses to ingestion of different sources of fat. Unique meals of three margarines used in human feeding were compared with a meal of lard with regard to their effects on hypothalamic 5-HT, satiety, anxiety-like behavior and sucrose consumption. A vegetable margarine with a high content in saturated fatty acids also decreased hypothalamic 5-HT while ingestion of a sunflower oil and an olive oil enriched margarines, both high in polyunsaturated fatty acids, did not affect significantly 5-HT levels. However, these two last ones were not the most satiating. The olive oil margarine induced a tendency to an anxiety-like behavior while lard increased sucrose consumption. Thus, ingestion of fats may alter specifically behavioral responses. The involvement of 5-HT is likely in the case of lard ingestion but probably not for the other sources of fat.