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Introduction It is well known that aging is associated with major quantitative changes in body composition; fat mass increases while lean body mass decreases. However, probably more important than the [...], Aging is associated with a redistribution of both fat and lean tissue within the body. Intra-abdominal fat (IAF) accumulates more rapidly than total fat while the loss of lean body mass is mostly due to sarcopenia. Increase of visceral fat plays a major role in the pathogenesis of insulin resistance, which leads to type II diabetes and also to cardiovascular diseases. This review is focussed on the relationships that exist between the accumulation of IAF and insulin resistance during aging. The various methods available for assessing IAF are briefly reviewed; imaging techniques are the only reference methods, and their availability is limited. Insulin resistance that appears with aging is caused by accumulation of IAF, rather than by aging per se. Studies done in type II diabetic patients suggest that the metabolic link between increased IAF and insulin resistance could well be the increased availability and/or oxidation of free fatty acids. Physical inactivity certainly enhances both IAF accumulation and, more directly, insulin resistance. Independent and significant effects of menopause or of sarcopenia on insulin resistance remain to be established. The influence of hormonal changes, reduced fatty acid utilization, and resistance to leptin on IAF accumulation are also discussed. Although it is difficult to determine the independent influence of each of these factors, IAF accumulation seems to be a central and important determinant of cardiovascular risk. The last part of this review is devoted to protein metabolism and focused on the preservation of protein metabolism in the liver during aging. Descriptors: aging; fat distribution; lean body mass

Introduction Dietary trans isomers of mono-unsaturated fatty acids, formed during partial hydrogenation of edible oils or by intestinal fermentation in ruminants, have been linked with an increased risk of coronary [...], Objective: To collect (i) baseline data and (ii) execute a large multicentre study examining the effect of trans α-linolenic acid on its incorporation into plasma lipids and on risk factors for coronary heart disease. Design: Male volunteers were recruited and the habitual diet assessed by a 4-d weighed record. Fatty acid composition of plasma and platelet lipids were determined by gas chromatography at baseline. After a 6 week run-in period on a trans 'free' diet, male volunteers were randomised to consume 0.6 % of energy trans α-linolenic acid or to continue with a diet 'low' in trans α-linolenic acid for 6 weeks. Setting: Three European university research departments supported by the research and development departments of the food industry. Subjects: Male volunteers (88) recruited by local advertisement. Methods: Replacement of 30 % of the fat of the habitual diet by margarine, oil and foods. Rapeseed oil was deodorised especially to produce the trans 'free' and 'high' trans foods for this study. The incorporation and conversion of trans α-linolenic acid into plasma lipids and platelets was assessed by gas chromatography and dietary compliance was verified by 4-d weighed record. Results: Less trans α-linolenic acid isomers are incorporated into human plasma lipids in French volunteers than in Dutch or Scottish volunteers consuming their habitual diets. Trans 'free' α-linolenic acid-rich oil can be produced by careful deodorization during refining. The 'high' trans diet provided 1410 ± 42 mg/d trans isomers of α-linolenic acid, whilst the 'low' trans group consumed 60 ± 75 mg/d. The change in plasma lipid and platelet fatty acid composition documented that trans linolenic isomers are incorporated and converted to a trans isomer of eicosapentaenoic acid. Only the 15-Tans α-linolenic acid is incorporated into plasma cholesteryl esters. The group consuming low trans diet had a slightly higher intake of fat, especially saturated and monounsaturated fat. Conclusions: Trans 'free' rapeseed oil, rich in α-linolenic acid, can be produced by careful deodorization. Dietary records show good compliance. Dietary trans isomers of α-linolenic acid are incorporated in plasma lipids and converted to long-chain polyunsaturated fatty acids. Their effects on risk factors for coronary heart disease and their metabolism will be reported elsewhere. Sponsorship: European Commission (FAIR 95-0594 grant). Descriptors: α-linolenic acid; trans fatty acid; diet; trial; fatty acid composition; plasma lipids; deodorization; trans polyunsaturated fatty acids

Introduction The data on which the following statements are based are almost exclusively from studies performed on healthy elderly individuals from high-income countries. There are few if any data documenting [...]

To assess the influence of age on vitamin A intestinal and liver metabolism in humans, the postprandial plasma concentrations of intestinal-originated vitamin A, i.e., retinyl esters, and liver-originated vitamin A, i.e., retinol, were compared in eight young (20-30 years old) and eight elderly (64-72 years old) healthy men. Plasma and chylomicron retinyl esters and retinol concentrations were measured for up to 24 h following the intake of a test meal that contained 23,300 RE retinyl palmitate. The chylomicron retinyl palmitate response (area under the curve) was not significantly different between the two groups, but its peak was slightly delayed (1 h) in the elderly men. The proportion of the different retinyl esters secreted in the chylomicrons was not significantly different between the two groups. The postprandial plasma retinol concentration did not change in the young participants, whereas it significantly increased in the elderly. These results suggest that vitamin A intestinal absorption and retinol intestinal esterification processes are not markedly modified in the elderly, whereas the chylomicron clearance and the regulation of postprandial plasma retinol concentration are apparently altered in these subjects. [ABSTRACT FROM AUTHOR]

In Bolivia, malnutrition in children is a major health problem that may be caused by inadequate protein, energy, and micronutrient intake; exposure to bacterial and parasitic infections; and life in a multistress environment (high altitude, cold, cosmic radiation, low ambient humidity). However, no data on protein absorption and utilization at high altitude were available. Therefore, we evaluated the effect of altitude on protein metabolism in Bolivian children. We measured protein utilization using leucine labeled with a stable isotope ((13)C) in two groups of healthy prepubertal children matched for age. Group 1 (n = 10) was examined at high altitude (HA) in La Paz (3600 m), and group 2 (n = 10) at low altitude (LA) in Santa Cruz (420 m). The nutritional status did not differ between groups but, as was to be expected, the HA group had higher hemoglobin concentration than the LA group. The children consumed casein that was intrinsically labeled with L-(1-(13)C) leucine and expired (13)CO(2) was analyzed. Samples of expired air were measured by isotope ratio mass spectrometer in Clermont-Ferrand. It was found that cumulative leucine oxidation ((13)CO(2)) at 300 min after ingestion was 19.7 +/- 4.9% at HA and 25.2 +/- 3.2% at LA. These results showed that protein absorption and/or utilization is significantly affected by altitude.

Several lines of evidence suggest that carotenoids may have a beneficial effect on health as a result of their antioxidant properties. In addition to beta-carotene, five other carotenoids are recovered in noticeable amounts from human plasma and tissues. Although the effect of beta-carotene on in vivo lipid peroxidation has been documented, few data are available on the effects of the other carotenoids. We evaluated the ability of the main human carotenoids to reduce lipid peroxidation by determining the correlations between plasma carotenoid concentration and plasma antioxidant capacity (in 79 healthy volunteers) and between carotenoid status and breath pentane excretion (in a subgroup of 24 subjects). Carotenoid intake was assessed by means of a 3-day food recall. Carotenoid status was evaluated by measurement of beta-carotene, lycopene, lutein/zeaxanthin, and alpha-carotene in plasma and buccal mucosal cells. Antioxidant status was evaluated by measurement of the total antioxidant capacity of the plasma. Oxidative stress status was evaluated by breath pentane measurements. Food recall data and the carotenoid concentrations in plasma and buccal mucosal cells showed that the subjects had normal carotenoid intake and normal carotenoid status. The total antioxidant capacity of the plasma was not related to the concentration of any specific carotenoid. The level of expired air pentane was not related to the carotenoid status of the subjects. These results show that normal concentrations of carotenoids in plasma and tissues are not correlated with these clinical markers of antioxidant and oxidative stress status.

During aging, there are qualitative and quantitative modifications of proteins in various tissues. In muscle, myofibrillar and mitochondrial proteins are affected, resulting in a loss of strength and, to a lesser degree, endurance. Mechanisms of sarcopenia remain not well known and probably involve loss of motoneurons, muscle disuse and hormonal alterations. Partial prevention of muscle loss is possible by resistance training. In all tissues, and particularly in the brain, oxidative changes in proteins are likely to alter various functions of proteins.

Whether tracers of different essential amino acids yield the same estimates of body protein turnover is still uncertain. Therefore, we have simultaneously determined leucine (Leu; using [14C]Leu), phenylalanine (Phe; using [13C]Phe), and tyrosine (Tyr; using [2H2]Tyr) rates of appearance (Ra) from proteolysis (PD), as well as Leu and Phe disposal, into protein synthesis (PS) both before and after an anabolic stimulus in healthy volunteers. Protein anabolism was stimulated by insulin plus a branched-chain amino acid-enriched aromatic amino acid-deficient amino acid solution, which increased Leu (from 145 +/- 9 to 266 +/- 10 mumol/l) but decreased Phe (from 57 +/- 2 to 46 +/- 3) and Tyr (from 58.7 +/- 5.5 to 21.0 +/- 2.2) concentrations. Postabsorptive endogenous Leu Ra (2.04 +/- 0.12 mumol.kg-1.min-1), Phe Ra (0.66 +/- 0.03), and Tyr Ra (0.45 +/- 0.06), as well as rates of PS determined with the leucine (1.65 +/- 0.10 mumol.kg-1.min-1) and the phenylalanine tracer (0.57 +/- 0.03), agreed well with the known abundance of these amino acids in body protein(s). After insulin and amino acids, PD was suppressed (P < 0.001) using all tracers. However, although percent suppression of endogenous Leu Ra (-->1.49 +/- 0.10 mumol.kg-1.min-1, 26 +/- 5%) and Phe Ra (-->0.53 +/- 0.02 mumol.kg-1.min-1, -20 +/- 2%) were comparable, endogenous Tyr Ra was suppressed to a larger extent (-->0.23 +/- 0.02 mumol.kg-1.min-1, -46 +/- 3% P = 0.038). PS was stimulated using the Leu (+24 +/- 7%, P < 0.02) but not the Phe (+6 +/- 4%, not significant) data. We conclude that isotopes of different essential amino acid: provide comparable estimates of PD and PS in the postabsorptive state. However, their responses to an anabolic stimulus may differ, possibly depending on exogenous amino acid availability and/or the resulting plasma levels.

The estimation of the hepatic protein synthesis precursor pool was investigated through the measurement of very low-density lipoprotein (VLDL) apolipoprotein (apo)B100 labeling in healthy volunteers. L-[1-13C]leucine and L-[5,5,5-2H3]leucine were administered intravenously and intragastrically, respectively. Subjects were continuously fed with isoenergetic meals providing either 16% protein or no protein. The labeling of leucine incorporated into VLDL apoB100 (leucine-apoB) was lower than plasma leucine or alpha-ketoisocaproate (KIC) enrichments with the intravenous tracer. By contrast, with the oral tracer, leucine-apoB enrichment was higher than either plasma free leucine or KIC labeling. The KIC and leucine-apoB enrichments relative to plasma leucine enrichment were not affected by protein intake. Albumin or fibrinogen synthesis rates were similar whatever the administration route of the tracer when leucine-apoB was used to indicate the precursor, which was not the case for plasma leucine or KIC. The present data suggest that leucine-apoB enrichment represents a reliable indicator of the hepatic precursor pool for protein synthesis. The effect of dietary protein on the calculated rates of albumin and fibrinogen synthesis is also reported in relation to the choice of the precursor.

The cellular mechanisms responsible for enhanced muscle protein breakdown in hospitalized patients, which frequently results in lean body wasting, are unknown. To determine whether the lysosomal, Ca2+-activated, and ubiquitin-proteasome proteolytic pathways are activated, we measured mRNA levels for components of these processes in muscle biopsies from severe head trauma patients. These patients exhibited negative nitrogen balance and increased rates of whole-body protein breakdown (assessed by [13C]leucine infusion) and of myofibrillar protein breakdown (assessed by 3-methylhistidine urinary excretion). Increased muscle mRNA levels for cathepsin D, m-calpain, and critical components of the ubiquitin proteolytic pathway (i.e., ubiquitin, the 14-kDa ubiquitin-conjugating enzyme E2, and proteasome subunits) paralleled these metabolic adaptations. The data clearly support a role for multiple proteolytic processes in increased muscle proteolysis. The ubiquitin proteolytic pathway could be activated by altered glucocorticoid production and/or increased circulating levels of interleukin 1beta and interleukin 6 observed in head trauma patients and account for the breakdown of myofibrillar proteins, as was recently reported in animal studies.

Total body water (TBW) and body composition are crucial for the estimation of nutritional status in many clinical circumstances. While the measurement of TBW with 18O-enriched water is technically easier than with 2H2O, the cost of 10% 18O-enriched water can be regarded as prohibitive. The aim of this study was to prove that less enriched (i.e. 2%) and cheaper (about 25 ECU per dose per subject, i.e. $30) 18O water can be used to measure TBW. In the 41 subjects studied, isotopic equilibrium was achieved 4 hours after the isotope was administered. Plateau enrichments in urine, saliva, and plasma samples did not differ significantly between 5 and 8 hours after the dose. TBW measurements in 8 of these subjects showed no significant differences, regardless of whether 2% or 10% water was used. We conclude that accurate estimates of TBW and body composition can be obtained with low-cost, 2% 18O-enriched water.

To investigate whether recombinant human insulin-like growth factor-I (rhIGF-I) could serve as a protein-sparing nondiabetogenic agent, 21 healthy volunteers (mean age, 25 +/- 1 yr) were studied in 3 similar clinical models: rhIGF-I alone, rhIGF-I and prednisone, and prednisone alone. In study A, 6 subjects received infusions of [14C]leucine and [2H2]glucose before and after 5-7 days of rhIGF-I (100 micrograms/kg, sc, twice daily, followed by 16 h of a 10 micrograms/kg.h continuous sc infusion). The rate of appearance (Ra) of leucine, an estimate of whole body proteolysis, did not change significantly, whereas leucine oxidation decreased (-31 +/- 4%; P = 0.001), hence the nonoxidative leucine disposal (NOLD) increased significantly (P = 0.04). These effects are similar to those reported with high dose hGH. Plasma glucose concentrations did not change despite a significant reduction in circulating insulin concentrations (-58 +/- 11%; P = 0.01) and an increase in the glucose Ra (+12 +/- 5%; P = 0.04). After rhIGF-I treatment, plasma IGF-I, IGF-binding protein-1 (IGFBP-1), and IGFBP-2 all increased significantly, whereas IGFBP-3 did not change. In study B, seven subjects received rhIGF-I combined with oral prednisone (0.8 mg/kg.day) for 5 days. Group C (n = 8) received only prednisone. In group B, both the leucine Ra and oxidation increased (Ra, +7 +/- 3%; oxidation, +45 +/- 13%), but this increase was significantly less than that seen in group C (Ra, +25 +/- 5%; oxidation, 117 +/- 17%; P < 0.005 vs. group B). Group B showed no significant changes in postabsorptive glucose concentrations despite marked reductions in circulating insulin levels, in contrast to the increase in insulin and glucose concentrations observed in group C. In conclusion, 100 micrograms/g rhIGF-I, given twice daily, 1) has GH-like effects on whole body protein metabolism, 2) markedly diminishes the protein catabolic effect of glucocorticosteroids, and 3) is nondiabetogenic in prednisone-treated humans. This agent offers promise in the treatment of protein catabolic states.

To determine the independent effects of insulin and glucose on the rate of appearance of leucine in humans, five normal volunteers were studied using a pancreatic clamp with sequential insulin infusions of 1.8, 3.6 and 7.2 pmol kg/min-1. On each of three separate occasions, the plasma glucose level was maintained at 5.0, 9.4 or 14 mM. The rate of appearance of leucine was similar at each insulin infusion rate regardless of the ambient glucose concentration or the glucose infusion rate. These studies demonstrate that during insulin and glucose infusion, insulin, but neither the plasma glucose concentration nor the rate of glucose utilization, primarily regulates leucine flux (a reflection of endogenous whole body proteolysis) in normal humans.