Dwight E. Matthews

Discrepancy between Self-Reported and Actual Caloric Intake and Exercise in Obese Subjects

BACKGROUND AND METHODS Some obese subjects repeatedly fail to lose weight even though they report restricting their caloric intake to less than 1200 kcal per day. We studied two explanations for this apparent resistance to diet--low total energy expenditure and underreporting of caloric intake--in 224 consecutive obese subjects presenting for treatment. Group 1 consisted of nine women and one man with a history of diet resistance in whom we evaluated total energy expenditure and its main thermogenic components and actual energy intake for 14 days by indirect calorimetry and analysis of body composition. Group 2, subgroups of which served as controls in the various evaluations, consisted of 67 women and 13 men with no history of diet resistance. RESULTS Total energy expenditure and resting metabolic rate in the subjects with diet resistance (group 1) were within 5 percent of the predicted values for body composition, and there was no significant difference between groups 1 and 2 in the thermic effects of food and exercise. Low energy expenditure was thus excluded as a mechanism of self-reported diet resistance. In contrast, the subjects in group 1 underreported their actual food intake by an average (+/- SD) of 47 +/- 16 percent and overreported their physical activity by 51 +/- 75 percent. Although the subjects in group 1 had no distinct psychopathologic characteristics, they perceived a genetic cause for their obesity, used thyroid medication at a high frequency, and described their eating behavior as relatively normal (all P < 0.05 as compared with group 2). CONCLUSIONS The failure of some obese subjects to lose weight while eating a diet they report as low in calories is due to an energy intake substantially higher than reported and an overestimation of physical activity, not to an abnormality in thermogenesis.

Relationship of plasma leucine and α-ketoisocaproate during a L-[1-13C]leucine infusion in man: A method for measuring human intracellular leucine tracer enrichment☆

The keto analog of leucine, alpha-ketoisocaproate (KIC), is formed intracellularly from leucine and is released, in part, into the systemic circulation. Therefore. KIC can be used to estimate intracellular leucine tracer enrichment in man during labeled-leucine tracer experiments without requiring tissue biopsy samples. This approach was studied in young, healthy, male adults maintained on different dietary protein intakes from generous (1.5 g kg-1d-1) to deficient (0.0 g kg-1d-1) for 5-7 day periods. At the end of each dietary period, the volunteers were given a primed, continuous infusion of L-[1-13C]leucine either after an overnight fast (postabsorptive state) or while being fed hourly aliquots of the same diet. The plasma concentrations of all 3 branched-chain amino and keto acid pairs were measured from early morning blood samples taken from 4 subjects at 4 different levels of protein intake. Leucine concentration showed a weak correlation, and valine concentration showed a strong correlation with protein intake; isoleucine and the 3 keto acids did not. However, each branched-chain amino acid concentration was strongly correlated with its corresponding keto acid concentration. In plasma samples obtained during the L-[1-13C]leucine infusions, the ratio of [1-13C]KIC to [1-13C]leucine enrichment ratio remained relatively constant (77 +/- 1% over the wide range of dietary protein intakes and for both the fed and postabsorptive states. For the tissues from which the plasma KIC originates, the rate of plasma leucine into cells will account for approximately 77% of the intracellular leucine flux with the remaining 23% coming primarily from leucine release via protein breakdown. The constant nature of the plasma KIC to leucine 13C enrichment ratio implies that relative changes in leucine kinetics will appear the same under many dietary circumstances regardless of whether plasma leucine or KIC enrichments are used for the calculations.

Phosphorylation by p38 MAPK as an alternative pathway for GSK3beta inactivation

Glycogen synthase kinase 3β (GSK3β) is involved in metabolism, neurodegeneration, and cancer. Inhibition of GSK3β activity is the primary mechanism that regulates this widely expressed active kinase. Although the protein kinase Akt inhibits GSK3β by phosphorylation at the N terminus, preventing Akt-mediated phosphorylation does not affect the cell-survival pathway activated through the GSK3β substrate β-catenin. Here, we show that p38 mitogen-activated protein kinase (MAPK) also inactivates GSK3β by direct phosphorylation at its C terminus, and this inactivation can lead to an accumulation of β-catenin. p38 MAPK–mediated phosphorylation of GSK3β occurs primarily in the brain and thymocytes. Activation of β-catenin–mediated signaling through GSK3β inhibition provides a potential mechanism for p38 MAPK–mediated survival in specific tissues.

Insulin-mediated reduction of whole body protein breakdown. Dose-response effects on leucine metabolism in postabsorptive men.

In vivo effects of insulin on plasma leucine and alanine kinetics were determined in healthy postabsorptive young men (n = 5) employing 360-min primed, constant infusions of L-[1-13C]leucine and L-[15N]alanine during separate single rate euglycemic insulin infusions. Serum insulin concentrations of 16.4 +/- 0.8, 29.1 +/- 2.7, 75.3 +/- 5.0, and 2,407 +/- 56 microU/ml were achieved. Changes in plasma 3-methyl-histidine (3-MeHis) were obtained as an independent qualitative indicator of insulin-mediated reduction in proteolysis. Hepatic glucose output was evaluated at the lowest insulin level using D-[6,6-2H2]glucose. The data demonstrate a dose-response effect of insulin to reduce leucine flux, from basal values of 77 +/- 1 to 70 +/- 2, 64 +/- 3, 57 +/- 3, and 52 +/- 4 mumol(kg X h)-1 at the 16, 29, 75, and 2,407 microU/ml insulin levels, respectively (P less than 0.01). A parallel, progressive reduction in 3-MeHis from 5.8 +/- 0.3 to 4.3 +/- 0.3 microM was revealed. Leucine oxidation estimated from the 13C-enrichment of expired CO2 and plasma leucine (12 +/- 1 mumol[kg X h]-1) and from the 13C-enrichment of CO2 and plasma alpha-ketoisocaproate (19 +/- 2 mumol[kg X h]-1) increased at the 16 microU/ml insulin level to 16 +/- 1 and 24 +/- 2 mumol(kg X h)-1, respectively (P less than 0.05 for each), but did not increase at higher insulin levels. Alanine flux (206 +/- 13 mumol(kg X h)-1) did not increase during the clamp, but alanine de novo synthesis increased in all studies from basal rates of 150 +/- 13 to 168 +/- 23, 185 +/- 21, 213 +/- 29, and 187 +/- 15 mumol(kg X h)-1 at 16, 29, 75, and 2,407 microU/ml insulin levels, respectively (P less than 0.05). These data indicate the presence of insulin-dependent suppression of leucine entry into the plasma compartment in man secondary to a reduction in proteolysis and the stimulation of alanine synthesis during euglycemic hyperinsulinemia.

Dynamic redox control of NF-kappaB through glutaredoxin-regulated S-glutathionylation of inhibitory kappaB kinase beta

The transcription factor NF-κB, a central regulator of immunity, is subject to regulation by redox changes. We now report that cysteine-179 of the inhibitory κB kinase (IKK) β-subunit of the IKK signalosome is a central target for oxidative inactivation by means of S-glutathionylation. S-glutathionylation of IKK-β Cys-179 is reversed by glutaredoxin (GRX), which restores kinase activity. Conversely, GRX1 knockdown sensitizes cells to oxidative inactivation of IKK-β and dampens TNF-α-induced IKK and NF-κB activation. Primary tracheal epithelial cells from Glrx1-deficient mice display reduced NF-κB DNA binding, RelA nuclear translocation, and MIP-2 (macrophage inflammatory protein 2) and keratinocyte-derived chemokine production in response to LPS. Collectively, these findings demonstrate the physiological relevance of the S-glutathionylation–GRX redox module in controlling the magnitude of activation of the NF-κB pathway.

Role of counterregulatory hormones in the catabolic response to stress.

Patients with major injury or illness develop protein wasting, hypermetabolism, and hyperglycemia with increased glucose flux. To assess the role of elevated counterregulatory hormones in this response, we simultaneously infused cortisol (6 mg/m2 per h), glucagon (4 ng/kg per min), epinephrine (0.6 microgram/m2 per min), and norepinephrine (0.8 micrograms/m2 per min) for 72 h into five obese subjects receiving only intravenous glucose (150 g/d). Four obese subjects received cortisol alone under identical conditions. Combined infusion maintained plasma hormone elevations typical of severe stress for 3 d. This caused a sustained increase in plasma glucose (60-80%), glucose production (100%), and total glucose flux (40%), despite persistent hyperinsulinemia. In contrast, resting metabolic rate changed little (9% rise, P = NS). Urinary nitrogen excretion promptly doubled and remained increased by approximately 4 g/d, reflecting increased excretion of urea and ammonia. Virtually all plasma amino acids declined. The increment in nitrogen excretion was similar in three additional combined infusion studies performed in 3-d fasted subjects not receiving glucose. Cortisol alone produced a smaller glycemic response (20-25%), an initially smaller insulin response, and a delayed rise in nitrogen excretion. By day 3, however, daily nitrogen excretion was equal to the combined group as was the elevation in plasma insulin. Most plasma amino acids rose rather than fell. In both infusion protocols nitrogen wasting was accompanied by only modest increments in 3-methylhistidine excretion (approximately 20-30%) and no significant change in leucine flux. We conclude: (a) Prolonged elevations of multiple stress hormones cause persistent hyperglycemia, increased glucose turnover, and increased nitrogen loss; (b) The sustained nitrogen loss is no greater than that produced by cortisol alone; (c) Glucagon, epinephrine, and norepinephrine transiently augment cortisol-induced nitrogen loss and persistently accentuate hyperglycemia; (d) Counterregulatory hormones contribute to, but are probably not the sole mediators of the massive nitrogen loss, muscle proteolysis, and hypermetabolism seen in some clinical settings of severe stress.

Literacy and body fatness are associated with underreporting of energy intake in US low-income women using the multiple-pass 24-hour recall : A doubly labeled water study

OBJECTIVE The accuracy of the multiple-pass 24-hour recall method for estimating energy intake in low-income women in the United States was ascertained by comparing the method with measurements of total energy expenditure. The multiple-pass 24-hour recall is designed to provide respondents with multiple cues and opportunities to report their food intake. It consists of 3 distinct passes: the quick list, detailed description, and review. Predictors of energy intake misreporting (energy intake--total energy expenditure) in the sample were determined. DESIGN Four multiple-pass 24-hour recalls (2 in person, 2 by telephone) were obtained over a 14-day period to estimate energy intake. Total energy expenditure was measured over the same 14-day period using the doubly labeled water method. Body composition was measured using dual energy x-ray absorptiometry, and literacy was measured by the Wide Range Achievement Test (WRAT) for reading and spelling. SUBJECTS/SETTINGS Thirty-five low-income women between the ages of 19 and 46 years were tested at the General Clinical Research Center at the University of Vermont, Burlington. Low income was defined as a household income at or below 130% of the federal poverty level. STATISTICAL ANALYSIS Pearson product moment correlation coefficients, t tests, paired t tests, and stepwise multiple regression analysis were used to test the relationships among study variables. RESULTS Mean energy intake was significantly lower than mean total energy expenditure (2,197 +/- 607 vs 2,644 +/- 503 kcal, P = .001) and the correlation between the 2 measures was poor (r = .22, P = .20). Percentage body fat and the combined age-adjusted reading and spelling WRAT scores were the best predictors of misreporting of energy intake (R = .52, P = .006). CONCLUSIONS The multiple-pass 24-hour recall did not generate a group measure of energy intake that was accurate or unbiased in this sample. Underreporting was strongly associated with increased body fatness. The ability to read and spell as measured by the WRAT improved the accuracy of the womens recall of their food intake. APPLICATIONS Dietetics professionals should take into consideration the problem of underreporting whenever conclusions are made about associations between diet and health and/or when evaluating the impact of food assistance programs on dietary intake.

Genome comparisons reveal a dominant mechanism of chromosome number reduction in grasses and accelerated genome evolution in Triticeae

Single-nucleotide polymorphism was used in the construction of an expressed sequence tag map of Aegilops tauschii, the diploid source of the wheat D genome. Comparisons of the map with the rice and sorghum genome sequences revealed 50 inversions and translocations; 2, 8, and 40 were assigned respectively to the rice, sorghum, and Ae. tauschii lineages, showing greatly accelerated genome evolution in the large Triticeae genomes. The reduction of the basic chromosome number from 12 to 7 in the Triticeae has taken place by a process during which an entire chromosome is inserted by its telomeres into a break in the centromeric region of another chromosome. The original centromere–telomere polarity of the chromosome arms is maintained in the new chromosome. An intrachromosomal telomere–telomere fusion resulting in a pericentric translocation of a chromosome segment or an entire arm accompanied or preceded the chromosome insertion in some instances. Insertional dysploidy has been recorded in three grass subfamilies and appears to be the dominant mechanism of basic chromosome number reduction in grasses. A total of 64% and 66% of Ae. tauschii genes were syntenic with sorghum and rice genes, respectively. Synteny was reduced in the vicinity of the termini of modern Ae. tauschii chromosomes but not in the vicinity of the ancient termini embedded in the Ae. tauschii chromosomes, suggesting that the dependence of synteny erosion on gene location along the centromere–telomere axis either evolved recently in the Triticeae phylogenetic lineage or its evolution was recently accelerated.

In-person vs Telephone-administered Multiple-pass 24-hour Recalls in Women: Validation with Doubly Labeled Water

OBJECTIVE To determine the accuracy of energy intakes estimated with the multiple-pass 24-hour recall method in women by conducting in-person and telephone interviews. Doubly labeled water measurements of total energy expenditure were used for validation. SUBJECTS Thirty-five weight-stable women (mean age = 30 years, range = 19 to 46 years) participated. DESIGN Total energy expenditure was measured over a 14-day period using the doubly labeled water method. During this time, 4 multiple-pass 24-hour recalls were obtained from the women (2 in-person, 2 by telephone) who were provided 2-dimensional food models to estimate portion sizes. The Food Intake Analysis System was used to analyze recall data. STATISTICAL ANALYSES Paired t tests were conducted to examine differences between energy intake estimated from the telephone and in-person interviews. Agreement between the energy intake estimates from the telephone recalls and the in-person recalls was assessed using the technique of Bland and Altman. Paired t tests were used to compare energy intake estimated from the telephone and in-person recalls to total energy expenditure. RESULTS No significant difference in mean daily energy intake was found between the telephone (2,253 +/- 688 kcal) and in-person (2,173 +/- 656 kcal) interviews (P = .36). However, the mean energy intake from each interview method was significantly lower than total energy expenditure (2,644 +/- 503 kcal) (P = .006 and .001, respectively). APPLICATIONS/CONCLUSIONS Underreporting of energy intake was widespread in the sample. Although the multiple-pass 24-hour recall method did not generate a group measure of energy intake that was accurate or unbiased, the telephone-administered multiple-pass 24-hour recall was just as effective in estimating energy intake as the recall administered in-person. Dietetics professionals should be aware of the pervasive and serious problem of under-reporting of self-reported food intakes.

Metabolic effects of very low calorie weight reduction diets.

A randomized comparison trial of two very low calorie weight reduction diets was carried out for 5 or 8 wk in 17 healthy obese women. One diet provided 1.5 g protein/kg ideal body weight; the other provided 0.8 g protein/kg ideal body weight plus 0.7 g carbohydrate/kg ideal body weight. The diets were isocaloric (500 kcal). Amino acid metabolism was studied by means of tracer infusions of L-[1-13C]leucine and L-[15N]alanine. After 3 wk of adaptation to the diets, nitrogen balance was zero for the 1.5 g protein diet but -2 g N/d for the 0.8 g protein diet. Postabsorptive plasma leucine and alanine flux decreased from base line by an equal extent with both diets by approximately 20 and 40%, respectively. It was concluded that protein intakes at the level of the recommended dietary allowance (0.8 g/kg) are not compatible with nitrogen equilibrium when the energy intake is severely restricted, and that nitrogen balance is improved by increasing the protein intake above that level. Basal rates of whole body nitrogen turnover are relatively well maintained, compared with total fasting, at both protein intakes. However, turnover in the peripheral compartment, as evidenced by alanine flux, may be markedly diminished with either diet.