Renal excretion ofγ-carboxyglutamic acid and metabolic rate in 3–18 years old humans

Summary The modified amino acid y-carboxyglutamic acid (Gla) occurs in several proteins such as prothrombin, blood coagulation factors VII, IX and X, proteins C, S and Z as well as matrix Gla protein and osteocalcin. The amount of Gla excreted in urine is a common indicator of the whole-body degradation of these proteins. We have determined the renal excretion rates of Gla in 3, 6,10,14 and 18 years old male and female human subjects (n = 14 per age group and sex) and calculated the respective resting metabolic rates (RMR) on the basis of the body weights using published formulas. We found high correlations between the excretion rates of Gla (µmol/d/kg body weight) and the RMR (kJ/d/kg body weight) in the females (n = 70) of r = 0.70 (y = 0.003x + 0.29) and in the males (n = 70) of r = 0.70 (y = 0.0038x + 0.27) and in all subjects (n = 140) of r = 0.69 (y = 0.0035x + 0.27); p < 0.01. We postulate that in children and adolescents a causal relationship exists between the whole-body degradation rate of Gla containing proteins and the metabolic rate.     

Age-related changes in the metabolism and body composition of three dog breeds and their relationship to life expectancy

We measured body composition and resting metabolic rates (RMR) of three dog breeds (Papillons, mean body mass 3.0 kg (n = 35), Labrador retrievers, mean body mass 29.8 kg (n = 35) and Great Danes, mean body mass 62.8 kg (n = 35)) that varied between 0.6 and 14.3 years of age. In Papillons, lean body mass (LBM) increased with age but fat mass (FBM) was constant; in Labradors, both LBM and FBM were constant with age, and in Great Danes, FBM increased with age but LBM was constant. FBM averaged 14.8% and 15.7% of body mass in Papillons and Labradors, respectively. Great Danes were leaner and averaged only 10.5% FBM. Pooling the data for all individuals, the RMR was significantly and positively associated with LBM and FBM and negatively associated with age. Once these factors had been taken into account there was still a significant breed effect on RMR, which was significantly lower in Labradors than in the other two breeds. Using the predictive multiple regression equation for RMR and the temporal trends in body composition, we modelled the expenditure of energy (at rest) over the first 8 years of life, and over the entire lifespan for each breed. Over the first 8 years of life the average expenditure of energy per kg LBM were 0.985, 0.675 and 0.662 GJ for Papillons, Labradors and Great Danes, respectively. This energy expenditure was almost 60% greater for the smallest compared with the largest breed. On average, however, the life expectancy for the smallest breed was a further 6 years (i.e. 14 years in total), whereas for the largest breed it was only another 6 months (i.e. 8.5 years in total). Total lifetime expenditure of energy at rest per kg LBM averaged 1.584, 0.918 and 0.691 GJ for Papillons, Labradors and Great Danes, respectively. In Labradors, total daily energy expenditure, measured by the doubly labelled water method in eight animals, was only 16% greater than the observed RMR. High energy expenditure in dogs appears positively linked to increased life expectancy, contrary to the finding across mammal species and within exotherms, yet resembling observations in other intra-specific studies. These contrasting correlations suggest that metabolism is affecting life expectancy in different ways at these different levels of enquiry.     

Influence of flavan-3-ols and procyanidins on UVC-mediated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine in isolated DNA

The flavan-3-ols (-)-epicatechin (epicatechin) and (+)-catechin (catechin) and their related oligomers (procyanidins) isolated from cocoa were assayed for their capacity to inhibit the UVC-mediated formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo(8)dG) in calf thymus DNA. The above-mentioned compounds inhibited oxo(8)dG production in a concentration- and time-dependent manner. After 30 min of irradiation (30 kJ/m(2)), 0.1, 1.0, 10, and 100 microM epicatechin inhibited oxo(8)dG formation by 20, 36, 64, and 74%, respectively. For the same dose of UVC, 0.1, 1.0, 10, and 100 microM catechin inhibited oxo(8)dG formation by 1, 23, 50, and 70%, respectively. Epicatechin was more efficient than catechin with respect to inhibiting oxo(8)dG formation (IC(50) 1.7 +/- 0.7 vs 4.0 +/- 0.7 microM). Monomer, tetramer, and hexamer fractions were equally effective in inhibiting oxo(8)dG formation when assayed at 10 microM monomer equivalent concentration. At similar concentrations (1-50 microM), the inhibition of the UVC-mediated oxo(8)dG formation by flavan-3-ols and procyanidins was in the range of that of alpha-tocopherol, Trolox, ascorbate, and glutathione. These results support the concept that flavan-3-ols and their related procyanidins can protect DNA from oxidation at concentrations that can be physiologically relevant. Both epimerism and degree of oligomerization are important determinants of the antioxidant activity of flavan-3-ols and procyanidins.     

A reliable assessment of 8-oxo-2-deoxyguanosine levels in nuclear and mitochondrial DNA using the sodium iodide method to isolate DNA

A major controversy in the area of DNA biochemistry concerns the actual in vivo levels of oxidative damage in DNA. We show here that 8-oxo-2-deoxyguanosine (oxo8dG) generation during DNA isolation is eliminated using the sodium iodide (NaI) isolation method and that the level of oxo8dG in nuclear DNA (nDNA) is almost one-hundredth of the level obtained using the classical phenol method. We found using NaI that the ratio of oxo8dG/10(5 )deoxyguanosine (dG) in nDNA isolated from mouse tissues ranged from 0.032 +/- 0.002 for liver to 0.015 +/- 0.003 for brain. We observed a significant increase (10-fold) in oxo8dG in nDNA isolated from liver tissue after 2 Gy of gamma-irradiation when NaI was used to isolate DNA. The turnover of oxo8dG in nDNA was rapid, e.g. disappearance of oxo8dG in the mouse liver in vivo after gamma-irradiation had a half-life of 11 min. The levels of oxo8dG in mitochondrial DNA isolated from liver, heart and brain were 6-, 16- and 23-fold higher than nDNA from these tissues. Thus, our results showed that the steady-state levels of oxo8dG in mouse tissues range from 180 to 360 lesions in the nuclear genome and from one to two lesions in 100 mitochondrial genomes.     

Renal excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine in Wistar rats with increased O(2) consumption due to cold stress

DNA damage by reactive oxygen species is of special interest in the development of cancer and in aging. The renally excreted amount of 8-oxo-7,8-dihydro-2'-deoxyguanosine (oxo(8)dG) is a potential noninvasive marker of oxidative DNA damage. The respiratory chain of mitochondria is one source for the formation of reactive oxygen species. In the present study we investigated in Wistar rats (n = 7; mean body weight at start, 307.4 +/- 11 g) the effect of an increased O(2) consumption, i.e., energy expenditure, due to cold stress on the renally excreted amount of oxo(8)dG. First, the rats were housed for 4 days at 23.5 degrees C (basic period, BP), and then for 6 days at 10 degrees C (cold stress period, CSP), and finally for 3 days at 23.5 degrees C (recovery period, RP). The O(2) consumption (L O(2)/day/kg weight) was significantly (P < 0.0001) on average 50% higher in CSP (69.0 +/- 3.9) than in BP (45.8 +/- 4.8), and similar in BP and RP (44.3 +/- 5.4). The average renal excretion of oxo(8)dG (pmol/day/kg weight) was significantly (P < 0.025) on average 13% higher in CSP (375.5 +/- 27.7) than in BP (333.2 +/- 47. 4) and similar in BP and RP (331.8 +/- 34.3). Maximum increase in oxo(8)dG excretion of on average 17% was on the third to fifth day of the CSP. This study reveals that an increase in O(2) consumption of 50% resulted in a much lower increase in the renal excretion of oxo(8)dG.     

DNA damage, repair, and antioxidant systems in brain regions: a correlative study

8-Hydroxy-2'-deoxyguanosine (oxo(8)dG) has been used as a marker of free radical damage to DNA and has been shown to accumulate during aging. Oxidative stress affects some brain regions more than others as demonstrated by regional differences in steady state oxo(8)dG levels in mouse brain. In our study, we have shown that regions such as the midbrain, caudate putamen, and hippocampus show high levels of oxo(8)dG in total DNA, although regions such as the cerebellum, cortex, and pons and medulla have lower levels. These regional differences in basal levels of DNA damage inversely correlate with the regional capacity to remove oxo(8)dG from DNA. Additionally, the activities of antioxidant enzymes (Cu/Zn superoxide dismutase, mitochondrial superoxide dismutase, and glutathione peroxidase) and the levels of the endogenous antioxidant glutathione are not predictors of the degree of free radical induced damage to DNA in different brain regions. Although each brain region has significant differences in antioxidant defenses, the capacity to excise the oxidized base from DNA seems to be the major determinant of the steady state levels of oxo(8)dG in each brain region.     

Energy expenditure adjusted for body composition differentiates constitutional thinness from both normal subjects and anorexia nervosa

Constitutional thinness (CT) is characterized by a low and stable body mass index (BMI) without any hormonal abnormality. To understand the weight steadiness, energetic metabolism was evaluated. Seven CT, seven controls, and six anorexia nervosa (AN) young women were compared. CT and AN had a BMI <16.5 kg/m(2). Four criteria were evaluated: 1) energy balance including diet record, resting metabolic rate (RMR) (indirect calorimetry), total energy expenditure (TEE) (doubly labeled water), physical activity; 2) body composition (dual-energy X-ray absorptiometry); 3) biological markers (leptin, IGF-I, free T3); 4) psychological profile of eating behavior. The normality of free T3 (3.7 +/- 0.5 pmol/l), IGF-I (225 +/- 93 ng/ml), and leptin (8.3 +/- 3.4 ng/ml) confirmed the absence of undernutrition in CT. Their psychological profiles revealed a weight gain desire. TEE (kJ/day) in CT (8,382 +/- 988) was not found significantly different from that of controls (8,793 +/- 845) and AN (8,001 +/- 2,152). CT food intake (7,565 +/- 908 kJ/day) was found similar to that of controls (7,961 +/- 1,452 kJ/day) and higher than in AN (4,894 +/- 703 kJ/day), thus explaining the energy metabolism balance. Fat-free mass (FFM) (kg) was similar in CT and AN (32.5 +/- 2.9 vs. 34.1 +/- 1.9) and higher in controls (37.8 +/- 1.6). While RMR absolute values (kJ/day) were lower in CT (4,839 +/- 473) than in controls (5,576 +/- 209), RMR values adjusted for FFM were the highest in CT. TEE-to-FFM ratio was also higher in CT than in controls. Energetic metabolism balance maintains a stable low weight in CT. An increased energy expenditure-to-FFM ratio differentiates CT from controls and could account for the resistance to weight gain observed in CT.     

Influence of Short‐Term Consumption of the Caffeine‐Free,Epigallocatechin‐3‐Gallate Supplement,Teavigo, on Resting Metabolism and the Thermic Effect of Feeding

Green tea is purported to promote weight loss. Resting metabolic rate (RMR) and the thermic effect of feeding (TEF) are significant components of total daily energy expenditure and are partially determined by the sympathetic nervous system via catecholamine‐mediated stimulation of β‐adrenergic receptors. Epigallocatechin‐3‐gallate (EGCG: the most bioactive catechin in green tea) inhibits catechol‐O‐methyltransferase, an enzyme contributing to the degradation of catecholamines. Accordingly, we hypothesized that short‐term consumption of a commercially available EGCG supplement (Teavigo) augments RMR and TEF. On two separate occasions, seven placebo or seven EGCG capsules (135 mg/capsule) were administered to 16 adults (9 males, 7 females, age 25 ± 2 years, BMI 24.6 ± 1.2 kg/m² (mean ± s.e.)). Capsules (three/day) were consumed over 48 h; the final capsule was consumed 2 h prior to visiting the laboratory. Energy expenditure (ventilated hood technique) was determined at rest and for 5 h following ingestion of a liquid meal (caloric content: 40% RMR). Contrary to our hypothesis, RMR was not greater (P = 0.10) following consumption of EGCG (6,740 ± 373 kJ/day) compared with placebo (6,971 ± 352). Similarly, the area under the TEF response curve (Δ energy expenditure) was also unaffected by EGCG (246,808 ± 23,748 vs. 243,270 ± 22,177 kJ; P = 0.88). EGCG had no effect on respiratory exchange ratio at rest (P = 0.29) or throughout the TEF measurement (P = 0.56). In summary, together RMR and TEF may account for up to 85% of total daily energy expenditure; we report that short‐term consumption of a commercially available EGCG supplement did not increase RMR or TEF.     

Physical activity in aging: comparison among young, aged, and nonagenarian individuals.

Physical activity (PA) is known to decline with age; however, there is a paucity of data on activity in persons who are in their nineties and beyond. We used objective and reliable methods to measure PA in nonagenarians (>or=90 yr; n=98) and hypothesized that activity would be similar to that of aged (60-74 yr; n=58) subjects but less than in young (20-34 yr; n=53) volunteers. Total energy expenditure (TEE) was measured by doubly labeled water over 14 days and resting metabolic rate (RMR) by indirect calorimetry. Measures of PA included activity energy expenditure adjusted for body composition, TEE adjusted for RMR, physical activity level (PAL), and activity over 14 days by accelerometry expressed as average daily durations of light and moderate activity. RMR and TEE were lower with increasing age group (P<0.01); however, RMR was not different between aged and nonagenarian subjects after adjusting for fat-free mass, fat mass, and sex. Nonagenarians had a lower PAL and were more sedentary than the aged and young groups (P<0.01); however, the nonagenarians who were more active on a daily basis walked further during a timed test, indicating higher physical functionality. For all measures of activity, no differences were found between young and aged volunteers. PA was markedly lower in nonagenarians compared with young and aged adults. Interestingly, PA was similar between young volunteers and those who were in their 60s and 70s, likely due to the sedentary nature of our society, particularly in young adults.     

DNA damage,p53 gene expression and p53 protein level in the rat brain aging

The aging induces free radicals leading to DNA damage (8‐oxo‐2′‐deoxyguanosine, 8‐oxo2dG). DNA injury causes increased expression of p53 gene and p53 protein. Levels of 8‐oxo2dG (HPLC), p53 mRNA (PCR) and p53 protein (Western blot) were estimated in gray matter (GM), white matter (WM), cerebellum (C) and medulla oblongata (MO) of control, 12‐ and 24‐month‐old rats. The level of 8‐oxo2dG increased with age in C (P < 0.05 in 12‐month‐old and P < 0.01 in 24‐month‐old rats) and MO. In 12‐month‐old animals the level of 8‐oxo2dG in GM and WM was higher than in controls. In 12‐month‐old animals p53 gene expression decreased while amounts of p53 protein increased, depending on the oxidative DNA damage. In 24‐month‐old rats, expression of p53 increased in all structures (P ≤ 0.05) while p53 protein showed decreased levels in most of structures of central nervous system (WM, C, MO). Aging leads to increased 8‐oxo2dG and augmented p53 gene expression, accompanied by a lowered expression of p53 protein.     

A fidelity mechanism in DNA polymerase lambda promotes error‐free bypass of 8‐oxo‐dG

8‐oxo‐7,8‐dihydroxy‐2′‐deoxyguanosine (8‐oxo‐dG) has high mutagenic potential as it is prone to mispair with deoxyadenine (dA). In order to maintain genomic integrity, post‐replicative 8‐oxo‐dG:dA mispairs are removed through DNA polymerase lambda (Pol λ)‐dependent MUTYH‐initiated base excision repair (BER). Here, we describe seven novel crystal structures and kinetic data that fully characterize 8‐oxo‐dG bypass by Pol λ. We demonstrate that Pol λ has a flexible active site that can tolerate 8‐oxo‐dG in either the anti‐ or syn‐conformation. Importantly, we show that discrimination against the pro‐mutagenic syn‐conformation occurs at the extension step and identify the residue responsible for this selectivity. This residue acts as a kinetic switch, shunting repair toward long‐patch BER upon correct dCMP incorporation, thus enhancing repair efficiency. Moreover, this switch also provides a potential mechanism to increase repair fidelity of MUTYH‐initiated BER.     

Energy Expenditure in Lean and Obese Prepubertal Children

The relationship between energy expenditure and obesity was examined in prepubertal children. Consenting fifth graders underwent Tanner Staging, weight, height and skinfold measurements. Subjects were selected for further study to obtain equal numbers of girls and boys with a wide range of body composition. Weight, total daily energy expenditure (TDEE) by doubly labeled water (DLW), resting metabolic rate (RMR), and body composition were measured. Children were grouped into level of obesity based on tertiles of subscapular plus triceps skinfolds. The skinfold tertiles did quite well in grouping subjects by degree of obesity, as differences in percent fat in each tertile were significantly different. There were no differences in fat-free mass between the groups, while the highest tertile group weighed 14 kg more than the lowest. For DLW, energy expenditure was calculated using day 8 and day 9 urine samples as the final time point to examine precision. Mean energy expenditure using either day was nearly identical (2220 ± 400 vs. 2300 ± 370 kcal/d), with a CV of the difference of 5.5%. No differences in RMR, energy expended in activity, or TDEE between the three groups were observed. A reduction in RMR or TDEE could not explain differences in obesity in these prepubertal children. However, the fact that the heaviest children expended the same amount of energy in activity and had the same TDEE as the leanest, while weighing 14 kg more, indicates that the obese children had a reduced activity level.     

Thermogenic response to insulin and glucose infusions in man: A model to evaluate the different components of the thermic effect of carbohydrate

The thermogenic response to an insulin and glucose infusion was determined in 10 healthy lean volunteers using a euglycemic clamp technique in conjunction with respiratory exchange measurements. The progressive rise in resting metabolic rate (RMR) from 4.295 ± 0.360 kJ/min during the baseline to 4.771 ± 0.410 kJ/min during the 90–120 min period of the euglycemic clamp (p < 0.01) correlated with the progressive increase in the glucose infusion rate (r = 0.836, p < 0.01), with the glucose storage rate (r = 0.812, p < 0.01), but not with the significant rise in insulin or norepinephrine concentrations. Storage of nutrients, as well as increased sympathetic nervous system (SNS) activity are known to increase RMR. Two thirds to three quarters of the observed increment in RMR following the insulin and glucose infusion in this study can be accounted for by the metabolic processing of the infused glucose for storage purposes. The rest of the thermogenic response (24–35%) must be explained by other mechanisms such as increased SNS activity.     

A meta-analysis of the effects of exercise and/or dietary restriction on resting metabolic rate

A meta-analysis was used to examine the independent and interactive effects of dietary restriction, endurance exercise training and gender on resting metabolic rate (RMR). Sixty different group means (covering 650 subjects) were identified from the scientific literature and subjected to meta-analysis techniques. Collectively (i.e., all groups combined), body weight loss was greater (P < 0.05) for men ( 18 kg) than for women ( 12 kg). There were no statistically significant exercise training or gender effects on RMR during weight loss. Collectively (i.e., all groups combined), dietary restriction resulted in a – 0.59 kJ min^–1 ( – 12%) decrease in RMR (P < 0.05). When normalized to body weight, RMR was reduced by less than 2% (P < 0.05). These data suggest that exercise training does not differentially affect RMR during diet-induced weight loss. In addition, decreases in resting metabolism appear to be proportional to the loss of the metabolically active tissue.     

Metabolic response to carbohydrate ingestion during exercise in males and females

The present study investigated potential sex-related differences in the metabolic response to carbohydrate (CHO) ingestion during exercise. Moderately endurance-trained men and women (n = 8 for each sex) performed 2 h of cycling at approximately 67% Vo(2 max) with water (WAT) or CHO ingestion (1.5 g of glucose/min). Substrate oxidation and kinetics were quantified during exercise using indirect calorimetry and stable isotope techniques ([(13)C]glucose ingestion, [6,6-(2)H(2)]glucose, and [(2)H(5)]glycerol infusion). In both sexes, CHO ingestion significantly increased the rates of appearance (R(a)) and disappearance (R(d)) of glucose during exercise compared with WAT ingestion [males: WAT, approximately 28-29 micromol x kg lean body mass (LBM)(-1) x min(-1); CHO, approximately 53 micromol x kg LBM(-1) x min(-1); females: WAT, approximately 28-29 micromol x kg LBM(-1) x min(-1); CHO, approximately 61 micromol x kg LBM(-1) x min(-1); main effect of trial, P < 0.05]. The contribution of plasma glucose oxidation to the energy yield was significantly increased with CHO ingestion in both sexes (from approximately 10% to approximately 20% of energy expenditure; main effect of trial, P < 0.05). Liver-derived glucose oxidation was reduced, although the rate of muscle glycogen oxidation was unaffected with CHO ingestion (males: WAT, 108 +/- 12 micromol x kg LBM(-1) x min(-1); CHO, 108 +/- 11 micromol x kg LBM(-1) x min(-1); females: WAT, 89 +/- 10 micromol x kg LBM(-1) x min(-1); CHO, 93 +/- 11 micromol x kg LBM(-1) x min(-1)). CHO ingestion reduced fat oxidation and lipolytic rate (R(a) glycerol) to a similar extent in both sexes. Finally, ingested CHO was oxidized at similar rates in men and women during exercise (peak rates of 0.70 +/- 0.08 and 0.65 +/- 0.06 g/min, respectively). The present investigation suggests that the metabolic response to CHO ingestion during exercise is largely similar in men and women.     

Effect of calorie restriction on the free-living physical activity levels of nonobese humans: results of three randomized trials

The objective of this study was to evaluate the influence of calorie restriction (CR) on free-living physical activity levels among humans. Data were from three CALERIE phase I site-specific protocols. Participants were nonobese (body mass index = 23.5-29.9 kg/m2 adults randomly assigned to 25% CR, low-calorie diet (LCD, 890 kcal/day supplement diet until 15% weight loss, then weight maintenance), or control at Pennington Biomedical Research Center (PBRC); 30% or 10% CR at Tufts University; and 20% CR or control at Washington University School of Medicine (WUSM). Activity was measured at months 0, 3, and 6 (PBRC) and at months 0, 3, 6, 9, and 12 (WUSM and Tufts). Total daily energy expenditure (TEE) by doubly labeled water and resting metabolic rate (RMR) were used to compute activity energy expenditure: AEE = TEE - RMR - 0.1 * TEE. Accelerometry and 7-day recall categorized activities by intensity. At Tufts, the 10% and 30% CR groups experienced significant decreases in AEE at months 6, 9, and 12. At month 6, a larger decrease in AEE was observed in the CR than the control group at WUSM. At months 3 and 6, larger decreases in AEE were observed in the CR and LCD groups than the control group at PBRC. Accelerometry and 7-day PAR did not consistently detect changes in activity categories. CR-associated changes in AEE were variable but, generally, reduced the energy deficit, which would reduce the expected rate of weight loss. Accelerometry and recall did not consistently explain reduced AEE, suggesting that increased muscle efficiency and/or decreased fidgeting accounted for decreased AEE. Inaccuracy of accelerometry and recall also likely negatively affected sensitivity.     

DNA sequence dependence of ATP hydrolysis by RecA protein

The DNA sequence dependence of the ATPase activity of RecA protein has been investigated for a variety of single strand octamer and hexadecamer homopolymers and alternating copolymers. Under assay conditions where the single strand DNA concentration exceeds the RecA protein concentration, significant differences in the rates of ATP hydrolysis for the various single strand DNA oligomer cofactors are observed. Under the conditions examined, the order of efficiency of the DNA cofactors in inducing RecA mediated ATPase activity is found to be: dA16 greater than dT16 greater than d(TC)16 greater than dT8 greater than dC16 greater than dA8 = dG8 greater than dG16 greater than dC8 greater than d(AG)16. These results demonstrate not only a dependence of RecA ATPase activity on the sequence composition of short single strand DNA they further reveal ATPase activity can be affected by the nearest neighbor nucleotide sequence of short DNA cofactors.     

Energetics and litter size variation in domestic dog Canis familiaris breeds of two sizes

We measured resting metabolic rate (RMR), daily energy expenditure (DEE) and metabolisable energy intake (MEI) in two breeds of dog during peak lactation to test whether litter size differences were a likely consequence of allometric variation in energetics. RMR of Labrador retrievers (30 kg, n=12) and miniature Schnauzers (6 kg, n=4) averaged 3437 and 1062 kJ/day, respectively. DEE of Labradors (n=6) and Schnauzers (n=4) averaged 9808 and 2619 kJ/day, respectively. MEI of Labradors (n=12) was 22448 kJ/day and of Schnauzers (n=7) was 5382 kJ/day. DEE of Labrador pups (2.13 kg, n=19) was 974 kJ/day and Schnauzers (0.89 kg, n=7) were 490 kJ/day. Although Labradors had higher MEIs than Schnauzers during peak lactation, there was no difference in mass-specific energy expenditure between the two breeds. Hence, it is unlikely that litter size variation is a likely consequence of differences in maternal energy expenditure. Individual offspring were relatively more costly for mothers of the smaller breed to produce. Therefore, litter size variations were consistent with the expectation that smaller offspring should be more costly for mothers, but not that smaller mothers should per se invest more resources in reproduction.     

Pattern and cost of weight gain in previously obese women

Weight gain is common among postobese individuals, providing an opportunity to address the cost of weight regain on energy expenditure. We investigated the energy cost of weight regain over 1 yr in 28 women [age 39.5 +/- 1.3 (SE) yr; body mass index 24.2 +/- 0.5 kg/m(2)] with recent weight loss (>12 kg). Body composition, total energy expenditure (TEE) using doubly labeled water, resting metabolic rate (RMR), and thermic effect of a meal (TEM) were assessed at 0 and 12 mo. Metabolizable energy intake (MEI) was calculated from TEE and change in body composition. Fourteen women had a weight gain of 13.2 +/- 2.1 kg. Twelve-month cumulative excess MEI, calculated as the intake in excess of TEE at month 0, was 749 +/- 149 MJ. Of this, 462 +/- 83 MJ (62%) were stored as accrued tissue, and 287 +/- 72 MJ (38%) was increased TEE. Expressed per kilogram of body weight gain, the energy cost of weight gain was calculated to be 54.8 +/- 4.6 MJ/kg. Interestingly, weight regain time courses fell into three distinct patterns, possibly requiring varying countermeasures.     

Oxidative DNA damage in humans: comparison between high and low habitual fruit and vegetable consumption

We investigated whether men with a habitual high consumption of vegetables and fruit have a lower excretion of 8 oxo 7,8 dihydro 2 deoxyguanosine 8 oxodG , a urinary marker for oxidative DNA damage, than men with a low consumption of vegetables and fruit. Ten pairs of healthy non smoking males aged between 28 and 59 years, matched for age 10 years and body mass index 2 kg m 2 were selected from a dietary validation study. Habitual food intake was estimated with 12 monthly 24 h recalls. Men in the high vegetable and fruit group consumed an average of 224 g day 1 range 101-330 g day 1 more vegetables and fruit than men in the low vegetable and fruit group. Excretion of 8 oxodG was 95 pmol kg 1 day 1 95 CI-29, 219 higher in the high vegetable and fruit group than in the low vegetable and fruit group paired t test, P = 0.11 . Excretion of 8 oxodG was not correlated with intake of vitamins, energy, fat, nor with blood concentrations of antioxidant pro vitamins, but it was inversely correlated with age. The present findings do not suggest that humans with a habitual high fruit and vegetables consumption have less oxidative DNA damage as measured by 8 oxodG excretion than men with low consumption of fruit and vegetables.