doi: 10.1152/physiolgenomics.00239.2007 You might find this additional info useful... Supplementary material for this article can be found at
Nutritional supplementation in childhood has positive effects on both the supplemented persons and on the subsequent generation.
Elevated plasma fatty acids have been shown to spare muscle glycogen during exercise. However, on the basis of recent findings, the saturation of fatty acids may influence this response. The purpose of this study was to determine whether saturated or unsaturated fatty acids affected muscle glycogenolysis to varying degrees during cycle exercise. Five healthy men completed three 60-min cycle ergometer trials (EX) at approximately 70% maximal O2 uptake (VO2max). Triglyceride levels were elevated by a fat feeding (FF) composed of 90% saturated fatty acids (heavy whipping cream, 90 g) or by the infusion of Intralipid (IL; Clintec Nutrition; 45 ml/h of 20% IL, 9.0 g), which was 85% unsaturated. A control trial (CON) consisted of a light breakfast (43 g carbohydrate and 1 g fat). Heparin (2,000 U) was administered 15 min before EX in FF and IL trials, resulting in one- and threefold increases in free fatty acid (FFA) levels in IL and FF, respectively. Pre-EX muscle glycogen did not differ. The utilization of muscle glycogen during 60 min of EX was less (P < 0.05) during the FF (60.0 +/- 5.2 mmol/kg wet wt) and IL (58.6 +/- 6.2 mmol/kg wet wt) compared with CON (81.8 +/- 7.5 mmol/kg wet wt). There was no difference between FF and IL in the amount of glycogen utilized. Serum triglyceride levels were greater (P < 0.05) at preheparin in FF (1.58 +/- 0.37 mmol/l) and IL (0.98 +/- 0.13 mmol/l) compared with CON (0.47 +/- 0.14 mmol/l).(ABSTRACT TRUNCATED AT 250 WORDS)
Aging alters the expression of a variety of genes. Calorie restriction (CR), which extends life span in laboratory rodents, also changes gene expression. This study investigated changes in gene expression across 3 different tissues from the same mouse to examine how aging and early stage CR influence gene expression in different tissues of an organism. Expression profiling of heart, liver, and hypothalamus tissues was done in young (4-6 months) ad libitum fed (AL), young CR (2.5-4.5 months of CR), and old (26-28 months) AL male C57BL/6 mice. Aging significantly altered the expressions of 309, 1819, and 1085 genes in heart, liver, and hypothalamus tissues, respectively. In 9 genes, aging altered expression across all 3 tissues although the regulation directions did not agree across all 3 tissues for some genes. Early stage CR in young mice significantly changed the expressions of 192, 839, and 100 genes in heart, liver, and hypothalamus tissues, respectively, and 7 genes altered expression across all 3 tissues; 3 were up regulated and 4 were down regulated. The results of Gene Ontology (GO) Biological Process analysis indicated up regulation of antigen processing/presentation genes by aging and down regulation of stress response genes by early stage CR in all 3 tissues. The comparison of the results of aging and short term CR studies showed there were 389 genes, 18 GO biological processes, and 20 GO molecular functions in common.
This study examined the impact of a 50% reduction in training frequency or training cessation on insulin action and muscle GLUT-4 protein concentration. Middle-aged individuals were tested before and after 12 wk of exercise training (4 days/wk, 40-45 min/day). Subjects then either maintained training (n = 9), reduced training frequency by 50% (n = 11), or stopped exercising (n = 10) for the ensuing 2 wk. GLUT-4 protein concentration and insulin action (insulin sensitivity index, as determined by the minimal model) increased (P < or = 0.05) by an average of 1.6- and 1.9-fold, respectively, with the 12 wk of training. Insulin action and GLUT-4 did not increase further with the additional 2 wk of training in the maintained training group. Similarly, insulin sensitivity index and GLUT-4 concentration remained at trained levels when training frequency was reduced by 50% for 2 wk. GLUT-4 concentration and insulin action, however, were not different from sedentary values after 14 days of training cessation. These findings indicate that a 14-day 50% reduction in exercise frequency maintains the improvements in GLUT-4 protein concentration and insulin action gained with endurance training in moderately trained middle-aged adults; in contrast, these adaptations are largely lost with training cessation.
Dietary restriction (DR) extends the life span and retards many age-related cellular and molecular changes in laboratory rodents. However, neither its underlying mechanism nor the limits of its action are fully understood. In this review, we assessed the effect of DR on gene expression in vertebrate and invertebrate animals using data generated by microarrays. Altered genes in DR mice reported in 15 articles published since 1999 were compared. A comparison of altered genes by DR in mice, rats, pigs, monkeys, yeast, and flies showed no common gene altered by DR among different species. It seems that individual genes altered in the expression by DR were constrained within species. When we compared the functions of altered genes across all species, we found that certain functions such as metabolism, energy metabolism, stress and immune response, cell growth, and transcription regulation were shared among species. Although individual genes seem to be affected by DR differently among species, the overall physiologic influence of DR may be similar.
Relative real-time reverse transcription PCR (RT-PCR) has become an important tool for quantifying changes in messenger RNA (mRNA) populations following differential development or stimulation of tissues or cells. However, the best methods for conducting such experiments and analyzing the resultant data remain an issue of discussion. In this report we describe an appropriate experimental methodology and the computer programs necessary to generate a meaningful statistical analysis of the combined biological and experimental variability in such experiments. Specifically, logarithmic transformations of raw fluorescence data from the log-linear portion of real-time PCR growth curves for both target and reference genes are analyzed using a SAS/STAT Mixed Procedure program specifically designed to give a point estimate of the relative expression ratio of the target gene with associated 95% confidence interval. The program code is open-source and is printed in the text.
Because food restriction (FR) has a profound effect on most tissues, it is plausible that the modulation of aging by FR occurs through cellular processes such as gene expression. The effect of FR in lowering plasma glucose levels has been demonstrated in mice, rats, and nonhuman primates. The consistency of this finding suggests that decreased plasma glucose may be an important consequence of FR. Indeed, lowering plasma glucose in the absence of FR would be expected to change the expression of some of the same genes as seen with FR. GLUT4 transgenic (TG) mice were particularly suited to this examination because they have low plasma glucose levels like FR mice. We investigated altered gene expression by FR and the effect of low plasma glucose levels caused by genetic manipulation by measuring mRNA expression in liver tissues of 4- to 6-mo-old mice with 2.5-4.5 mo of FR using microarrays and 4 groups: GLUT4 TG (C57BL/6 background) consumed food ad libitum (AL), GLUT4 TG FR, wild-type littermates AL, and wild-type littermates FR. The 3 statistical analysis methods commonly indicated that FR altered the expression of 1277 genes; however, none of these genes was altered by additional GLUT4 expression. In fact, the low plasma glucose level in GLUT4 TG mice did not affect gene expression. Some results were confirmed by real-time quantitative RT-PCR. We conclude that a low plasma glucose level does not contribute to or coincide with the effect of FR on gene expression in the liver.
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