Carol N. Boozer

Improving Energy Expenditure Estimation for Physical Activity

PURPOSE The purpose of this study was to validate the Intelligent Device for Energy Expenditure and Activity (IDEEA) for estimation of energy expenditure during a variety of activities. An additional aim was to improve the accuracy of the estimation of energy expenditure of physical activity based on second-by-second information of type, onset, and duration of activity. METHODS This study included two tests: a mask calorimetry test with 27 subjects [age = 33.7 +/- 13.8 (mean +/- SD) yr; BMI = 24.8 +/- 4.8 kg x m] and a respiratory chamber calorimetry test with 10 subjects (age = 32.9 +/- 12.4 yr; BMI = 26.1 +/- 5.6 kg x m). In the mask test, the subjects performed activities (sitting, standing, lying down, level treadmill walking, and running at different speeds) for 50-min durations. For the chamber test, subjects lived in the metabolic chamber for 23 h and performed three exercise sessions to compensate for the confined environment. RESULTS The results showed significant correlations (P < 0.0001) between energy expenditure estimated by IDEEA and energy expenditure measured by the calorimeters with an accuracy >95%. After corrections for the decrease in sleeping metabolic rate, the estimation accuracy for the chamber test was increased by 1-96.2%, whereas the estimation accuracy for nighttime activity was significantly improved by 4-99%. CONCLUSION IDEEA provides a suitable method for estimating the energy expenditure of physical activity. It provides both instantaneous and cumulative estimates of energy expenditure over a given period.

Targeted Deletion of the Vgf Gene Indicates that the Encoded Secretory Peptide Precursor Plays a Novel Role in the Regulation of Energy Balance

To determine the function of VGF, a secreted polypeptide that is synthesized by neurons, is abundant in the hypothalamus, and is regulated in the brain by electrical activity, injury, and the circadian clock, we generated knockout mice lacking Vgf. Homozygous mutants are small, hypermetabolic, hyperactive, and infertile, with markedly reduced leptin levels and fat stores and altered hypothalamic proopiomelanocortin (POMC), neuropeptide Y (NPY), and agouti-related peptide (AGRP) expression. Furthermore, VGF mRNA synthesis is induced in the hypothalamic arcuate nuclei of fasted normal mice. VGF therefore plays a critical role in the regulation of energy homeostasis, suggesting that the study of lean VGF mutant mice may provide insight into wasting disorders and, moreover, that pharmacological antagonism of VGF action(s) might constitute the basis for treatment of obesity.

Heterozygosity forLepob orLeprdb affects body composition and leptin homeostasis in adult mice

In an effort to understand the genetics of human obesity, we have studied the physiology and molecular genetics of rodent models with monogenetic forms of obesity including the leptin gene-defective ( Lepob / Lepob ) and leptin receptor gene-defective ( Leprdb / Leprdb ) mouse. In the experiments reported here, we investigated the effects of heterozygosity at Lepob and Leprdb on body composition and circulating leptin concentration in +/+, Leprdb /+, and Lepob /+ adult mice to identify possible gene dosage effects of these mutations that might elucidate their physiology. Adult mice heterozygous for the Lepob or Leprdb allele had equivalent fat mass and percentage body fat, which was increased 27-47% and 23-35%, respectively, relative to +/+ littermates. Plasma leptin concentrations adjusted for fat mass were 6.5 ng/ml in the Lepob /+, 9.6 ng/ml in the +/+, and 11.5 ng/ml in the Leprdb /+ mice. Sex had no effect on plasma leptin after controlling for fat mass. These data, and data from a small number of mice heterozygous at both Lepob and Leprdb (compound heterozygotes), suggest that leptin protein produced per mass of body fat is reduced in Lepob /+ mice and that body fat is increased in Lepob /+ mice until plasma leptin concentrations reach that of a normal +/+ mouse. The elevated plasma leptin concentration in the Leprdb /+ mice suggests that LEPR may mediate autocrine suppression of Lep expression. These results raise the possibility that human mutations that have even subtle effects on the leptin/leptin receptor system in either the homozygous or heterozygous state may have significant effects on adiposity.In an effort to understand the genetics of human obesity, we have studied the physiology and molecular genetics of rodent models with monogenetic forms of obesity including the leptin gene-defective (Lep(ob)/Lep(ob)) and leptin receptor gene-defective (Lep(rdb)/Lep(rdb)) mouse. In the experiments reported here, we investigated the effects of heterozygosity at Lep(ob) and Lep(rdb) on body composition and circulating leptin concentration in +/+, Lep(rdb)/+, and Lep(ob)/+ adult mice to identify possible gene dosage effects of these mutations that might elucidate their physiology. Adult mice heterozygous for the Lep(ob) or Lep(rdb) allele had equivalent fat mass and percentage body fat, which was increased 27-47% and 23-35%, respectively, relative to +/+ littermates. Plasma leptin concentrations adjusted for fat mass were 6.5 ng/ml in the Lep(ob)/+, 9.6 ng/ml in the +/+, and 11.5 ng/ml in the Lep(rdb)/+ mice. Sex had no effect on plasma leptin after controlling for fat mass. These data, and data from a small number of mice heterozygous at both Lep(ob) and Lep(rdb) (compound heterozygotes), suggest that leptin protein produced per mass of body fat is reduced in Lep(ob)/+ mice and that body fat is increased in Lep(ob)/+ mice until plasma leptin concentrations reach that of a normal +/+ mouse. The elevated plasma leptin concentration in the Lep(rdb)/+ mice suggests that LEPR may mediate autocrine suppression of Lep expression. These results raise the possibility that human mutations that have even subtle effects on the leptin/leptin receptor system in either the homozygous or heterozygous state may have significant effects on adiposity.

PROP taster status and oral fatty acid perception

Recent studies with rat taste cells treated with polyunsaturated fatty acids suggest that fatty acids may play a role in dietary fat perception. In humans, sensitivity to the textural properties of fat is associated with the genetic ability to taste the bitter compound 6-N-2-propylthiouracil (PROP). However, it has not been shown that PROP tasters are more sensitive in discriminating fatty acids in a high-fat food. Our study with human subjects was designed to test the hypothesis that the ability to orally detect food-grade conjugated linoleic acid added to high-fat vanilla ice cream is associated with the ability to taste PROP. Eighty percent of the PROP tasters in this study, but only 17% of the PROP nontasters correctly discriminated the sample containing the added free fatty acid in a difference test versus unadulterated high-fat vanilla ice cream (Fishers Exact Test, P=.05). Because most fatty foods contain minute amounts of free fatty acids, further studies with humans examining the contribution of fatty acids to fat perception seem warranted.

Harris–Benedict equation estimations of energy needs as compared to measured 24-h energy expenditure by indirect calorimetry in people with early to mid-stage Huntington's disease

Abstract Weight loss and energy metabolism are important clinical research areas in understanding the disease mechanisms in Huntingtons disease. Having an accurate method to estimate expected total energy expenditure would likely facilitate the development of studies about these features of the disease. The Harris–Benedict equation is a formula commonly used to estimate basal energy expenditure of individuals, adjusted for height, weight, age and gender. This estimate is then multiplied by a physical activity factor to estimate total daily energy needs to maintain the given weight. Data from 24-h indirect calorimetry was utilized to derive an adjustment formula for the physical activity factor of the Harris–Benedict equation for 13 early to mid-stage Huntingtons disease patients. The adjusted activity factor provided the most accurate estimate of energy needs. This adjusted formula can be used in clinical assessments of Huntingtons disease patients, as well as in research studies when indirect calorimetry has not been performed.

In-vivo assessment of total body protein in rats by prompt-γ neutron activation analysis

A prompt-(gamma) neutron activation analysis facility for in vivo determination of total body protein (TBP) in rats has been designed. TBP is determined in vivo by assessment of total body nitrogen. The facility is based on a 252Cf radionuclide neutron source within a heavy water moderator assembly and two NaI(Tl) scintillation detectors. The in vivo precision of the technique, as estimated by three repeated measurements of 15 rats is 6 percent, for a radiation dose equivalent of 60 mSv. The radiation dose per measurement is sufficiently low to enable serial measurements on the same animal. MCNP-4A Monte Carlo transport code was utilized to calculate thermal neutron flux correction factors to account for differences in size and shape of the rats and calibration phantoms. Good agrement was observed in comparing body nitrogen assessment by prompt-(gamma) neutron activation and chemical carcass analysis.