Centrally administered urocortin 2 decreases gorging on high-fat diet in both diet-induced obesity-prone and -resistant rats.

OBJECTIVE: Obesity is a costly, deadly public health problem for which new treatments are needed. Individual differences in meal pattern have been proposed to have a role in obesity risk. The present study tested the hypothesis that (i) the microstructure of chronic high-fat diet intake differs between genetically selected diet-induced obesity (DIO) and diet-resistant (DR) rats, and (ii) central administration of urocortin 2 (Ucn 2), a corticotropin-releasing factor type 2 agonist, decreases high-fat diet intake not only in lean DR rats, but also in obese DIO rats. DESIGN: Male, selectively bred DIO and DR rats (n=10/genotype) were chronically fed a high-fat diet. Food and water intake as well as ingestion microstructure were then compared under baseline conditions and following third intracerebroventricular injection of Ucn 2 (0, 0.1, 0.3, 1, 3 µg). RESULTS: Irrespective of genotype, Ucn 2 reduced nocturnal food intake with a minimum effective dose of 0.3 µg, suppressing high-fat diet intake by ∼40% at the 3 µg dose. Ucn 2 also made rats of both genotypes eat smaller and briefer meals, including at doses that did not reduce drinking. Obese DIO rats ate fewer but larger meals than DR rats, which they ate more quickly and consumed with two-third less water. CONCLUSIONS: Unlike leptin and insulin, Ucn 2 retains its full central anorectic efficacy to reduce high-fat diet intake even in obese, genetically prone DIO rats, which otherwise show a 'gorging' meal pattern. These results open new opportunities of investigation toward treating some forms of DIO.

No compelling evidence that sibutramine prolongs life in rodents despite providing a dose-dependent reduction in body weight.

OBJECTIVE: The health and longevity effects of body weight reduction resulting from exercise and caloric restriction in rodents are well known, but less is known about whether similar effects occur with weight reduction from the use of a pharmaceutical agent such as sibutramine, a serotonin-norepinephrine reuptake inhibitor. RESULTS AND CONCLUSION: Using data from a 2-year toxicology study of sibutramine in Sprague-Dawley CD rats and CD-1 mice, despite a dose-dependent reduction in food intake and body weight in rats compared with controls, and a body weight reduction in mice at the highest dose, there was no compelling evidence for reductions in mortality rate.

Therapeutic potential of genetically modified adult stem cells for osteopenia.

Adult stem cells have therapeutic potential because of their intrinsic capacity for self-renewal, especially for bone regeneration. The present study shows the utility of ex vivo modified mesenchymal stem cells (MSC) to enhance bone density in an immunocompetent mouse model of osteopenia. MSC were transduced ex vivo with a recombinant adeno-associated virus 2 (rAAV2) expressing bone morphogenetic protein 2 (BMP2) under the transcriptional control of collagen type-1alpha promoter. To enrich bone homing in vivo, we further modified the cells to transiently express the mouse alpha4 integrin. The modified MSC were systemically administered to ovariectomized, female C57BL/6 mice. Effects of the therapy were determined by dual-energy X-ray absorptiometry, 3D micro-CT, histology and immunohistochemistry for up to 6 months. Results indicated that mice transplanted with MSC expressing BMP2 showed significant increase in bone mineral density and bone mineral content (P < 0.001) with relatively better proliferative capabilities of bone marrow stromal cells and higher osteocompetent pool of cells compared to control animals. Micro-CT analysis of femora and other bone histomorphometric analyses indicated more trabecular bone following MSC-BMP2 therapy. Results obtained by transplanting genetically modified MSC from green fluorescent protein transgenic mouse suggested that production of BMP2 from transplanted MSC also influenced the mobilization of endogenous progenitors for new bone formation.

Visceral fat, insulin sensitivity, and lipids in prepubertal children.

In adults, visceral fat accumulation is associated with insulin resistance and dyslipidemia. The cause-and-effect nature of these relationships is not clear. The objective of the present study was to determine if similar relationships exist in prepubertal children. Specifically, we determined whether visceral fat was associated with fasting insulin, insulin sensitivity (Si), serum triglyceride (TG) concentration, or serum HDL cholesterol (HDL-C) concentration; whether visceral fat or Si was independently related to lipids; and whether ethnicity influenced the relationship between visceral fat and risk factors. Subjects were 61 prepubertal African-American and Caucasian children. Total body fat was determined by dual-energy X-ray absorptiometry, visceral fat by computed tomography, and insulin sensitivity by the tolbutamide-modified, frequently sampled intravenous glucose tolerance test with minimal modeling. In multiple linear regression analysis (adjusting for total fat, sex, and ethnicity), visceral fat was independently related to TG (P < 0.05) and fasting insulin (P < 0.001), but not Si (P = 0.425). Total body fat was independently related to Si (P < 0.001). Si was independently related to fasting insulin (P < 0.001) but not to TG or HDL-C (P = 0.941 and 0.201, respectively). Si in African-Americans was 42% lower than in Caucasians (0.50 +/- 0.05 vs. 0.86 +/- 0.11 x 10(-5) min(-1) x pmol(-1) x l, mean +/- SE after adjusting for total fat, P < 0.001). Nonetheless, ethnicity was not independently related to either TG or HDL-C (P = 0.075 and 0.619, respectively, after adjusting for total and visceral fat and sex). The slopes of the relationships of total and visceral fat with risk factors did not differ with ethnicity. In conclusion, visceral fat appears metabolically unique in children, being independently associated with elevated TG and insulin but not Si. Obese children and African-American children were more insulin resistant, independent of visceral fat accumulation. Lower Si was associated with higher, faster insulin, but not dyslipidemia. Thus, obesity, visceral fat accumulation, and ethnicity in children may confer negative, but independent, health risks.

Validation of peripheral dual-energy X-ray absorptiometry for the measurement of bone mineral in intact and excised long bones of rats.

We evaluated the precision and accuracy of peripheral dual-energy X-ray absorptiometry (DXA) for the measurement of bone mineral density (BMD) and bone mineral content (BMC) in intact and excised femurs and tibias from rats. Thirty-one Sprague-Dawley rats (18F/13M; 114-360 g) were used in the study. Precision and accuracy were determined in 23 rats and prediction equations were evaluated in an independent sample of 8 animals. Precision was determined by measuring the right hindquarter three times with repositioning between scans. The femur and tibia were then excised, cleaned, and scanned in triplicate, with repositioning. CVs ranged from 0.66 to 2.24%. Accuracy of BMC was determined by comparison to bone ash values. BMC values for the intact and excised femur significantly overestimated bone ash (p < 0.001) by 33% and 5.5%, respectively. BMC for the intact tibia overestimated ash by 37% (p < 0.001), whereas BMC for the excised tibia underestimated ash by 1% (p < 0.05). However, BMC and bone ash were highly related for both bones, whether BMC was measured in the intact animal or after excision (r2 > 0.99). Cross-validation of prediction equations in an independent sample showed that there were no significant differences between predicted ash (based on BMC from DXA) and measured bone ash. These results suggest the peripheral DXA is a useful tool for measuring intact and excised rat leg bones.

Serum leptin and energy expenditure in children.

Leptin has been hypothesized to play an important role in energy balance by affecting both energy intake and energy expenditure. The purpose of our study was to determine the relationship between fasting serum leptin concentrations and measures of energy expenditure in prepubertal children. We measured total energy expenditure (TEE; by the doubly labeled water technique), resting energy expenditure (REE; after an overnight fast), activity energy expenditure (AEE; TEE-REE), body composition (by dual energy x-ray absorptiometry), and fasting serum leptin concentration (by RIA) in 76 children. Simple correlations showed that all measures of energy expenditure (TEE, REE, and AEE) were positively related to the serum leptin concentration (r = 0.50, P < 0.001; r = 0.45, P < 0.001; and r = 0.30, P < 0.01, respectively). However, after adjusting for body composition (fat-free mass and fat mass), gender, and ethnicity, serum leptin concentrations were not related to any measure of energy expenditure (TEE, P = 0.61; REE, P = 0.97; AEE, P = 0.65). These latter findings were further confirmed using structural equation models with leptin and energy expenditure as dependent variables, and fat-free mass and fat mass as independent variables. Results from these models showed no direct effect of leptin and no indirect effect of fat mass (through leptin) on any measure of energy expenditure, when a path between fat mass and energy expenditure was present in the model. Thus, our data do not support the hypothesis that the serum leptin concentration (independent of fat mass) is related to measures of energy expenditure in children.

Leptin in postmenopausal women: influence of hormone therapy, insulin, and fat distribution.

Whether use of hormone-replacement therapy (HRT) influences menopause-related changes in body weight is unclear. HRT may affect energy balance by influencing synthesis of the adipocyte-derived hormone leptin. The objectives of this study were to: 1) identify factors influencing circulating leptin in postmenopausal women; 2) determine whether HRT influences serum leptin after adjusting for confounding factors; and, 3) identify potential independent effects of HRT or leptin on resting energy expenditure (REE). Subjects were 54 postmenopausal women, 45-55 yr old, 35 of whom used HRT (estrogen plus progestin). Total and regional body composition and fat distribution were determined by dual-energy x-ray absorptiometry and computed tomography; fasting serum leptin and insulin, by RIA; and REE, by indirect calorimetry. Stepwise multiple linear regression analysis indicated that serum leptin could best be predicted from total fat mass, fasting serum insulin, and total lean mass [log leptin = 1.08 x log fat mass) + (0.46 x log insulin) + (-1.25 x log lean mass) + 1.88; model R2 = 0.78, P < 0.001]. Multiple linear regression analysis indicated that visceral fat was independently related to leptin (parameter estimate = 0.23, P < 0.05), after adjusting for s.c. abdominal fat and leg fat, as well as lean mass and insulin. After adjusting for total fat mass, total lean mass, and fasting insulin, serum leptin did not differ between users and nonusers of HRT (21.7 +/- 1.0 vs. 20.2 +/- 1.3 ng/mL, P = 0.369, adjusted mean +/- SE, respectively). Serum estradiol was inversely correlated with (adjusted) leptin in non-HRT users (r = -0.50), suggesting that ovarian senescence may lead to an increase in leptin. Multiple linear regression analysis indicated that REE (adjusted for fat mass, fat-free mass, and ethnicity) was not associated with leptin (P = 0.298) or hormone use status (P = 0.999; 1323 +/- 31 vs. 1316 +/- 42 kcal/day, adjusted mean +/- SE for users and nonusers, respectively). These results indicate that, in postmenopausal women: 1) total fat mass, lean mass, and fasting insulin, but not HRT, are significant determinants of serum leptin; 2) visceral and s.c. fat contribute to serum leptin; and, 3) neither HRT nor leptin is independently related to REE.

Effects of gender, ethnicity, body composition, and fat distribution on serum leptin concentrations in children.

The Ob protein leptin has been shown to be closely correlated with measures of body fat in humans and animals. Studies have suggested that there are both gender and ethnic differences in serum leptin concentrations, even after controlling for total and relative body fat and body mass index. We hypothesized that gender and ethnic differences in serum leptin concentrations are due to differences in both body composition and body fat distribution. We measured fasting serum leptin concentration, body composition (fat mass and fat-free mass by dual energy x-ray absorptiometry), and body fat distribution (intraabdominal and sc abdominal adipose tissue by computed tomography) in 74 prepubertal boys and girls (43 African-Americans and 31 Caucasians). Our results showed that gender differences in serum leptin concentrations could not be fully explained by differences in body mass index, total fat mass, or relative body composition. However, when serum leptin concentrations were adjusted for differences in relative body composition (fat mass and fat-free mass) and body fat distribution (sc and intraabdominal adipose tissue), gender no longer had an independent effect on the serum leptin concentration. Serum leptin concentrations were not influenced by ethnicity. Thus, when comparing group differences in serum leptin concentrations, it is necessary to adequately control for group differences in body composition and fat distribution.

Cross-calibration of fat and lean measurements by dual-energy X-ray absorptiometry to pig carcass analysis in the pediatric body weight range.

The objective of this study was to cross-calibrate measurements of body composition by dual-energy X-ray absorptiometry (DXA) with chemical analysis of carcasses of pigs in the pediatric range of body weight. Eighteen pigs (25.5 +/- 7.0 kg; 9.9-32.8% body fat) were scanned in duplicate by using DXA with a Lunar DPX-L densitometer in the pediatric medium and adult fast-detail scan modes. Pigs were then killed and their carcasses analyzed completely. Carcass lean and fat contents were highly correlated with DXA measurement in both scan modes (Pearson r values > 0.98). For lean mass, the relation between carcass content and DXA measures was not significantly different from the line of identity in the adult mode, but was in the pediatric mode. For fat mass, the relations between carcass content and DXA measures were significantly different from the line of identity in both the adult and pediatric modes. In duplicate scans, the reliability of DXA measures of lean mass and fat mass was excellent in both scan modes. Because neither the adult nor the pediatric scan mode provided accurate measures of fat and lean mass, we derived specific correction factors to improve the measurement of total fat and lean compartments, thereby calibrating the Lunar DPX-L to the laboratory standard of carcass analysis in pigs.

Cross-calibration of body-composition techniques against dual-energy X-ray absorptiometry in young children.

Using dual-energy X-ray absorptiometry (DXA) as a standard method for determining body composition in children, we evaluated the accuracy of skinfold-thickness measurements (with the Slaughter et al equations, which are based on triceps and calf skinfold-thickness measurements), bioelectrical resistance (BR; with the Kushner el al equations and age-specific hydration constants), and other clinical measurements (individual skinfold thicknesses and body mass index) for the assessment of body fat in children. We studied a heterogenous group of 49 boys and 49 girls, aged 6.6 +/- 1.4 y and weighing 24.1 +/- 5.9 kg. Fat mass estimated by DXA was significantly lower than fat mass measured by skinfold thickness, even though fat mass measurements by these two techniques were strongly related to each other. Fat mass estimated by DXA was also significantly lower than fat mass measured by BR, and the model R2 and SEE were not as strong as for the skinfold-thickness technique. Fat mass estimated by DXA also correlated with other clinical indexes such as triceps skinfold thickness, body mass index, body weight, and subscapular skinfold thickness. In forward-regression analysis, subscapular skinfold thickness, body weight, triceps skinfold thickness, sex, and height2/resistance estimated the value for fat mass measured by DXA with a model R2 of 0.91 and an SEE of 0.94 kg fat mass. These studies suggest that existing techniques for assessing body fat in children may be inaccurate. We provide new anthropometric equations based on the use of DXA as a criterion that provide accurate and precise measures of body fat and fat-free mass in white children aged 4-9 y. This approach provides estimates of body fat standardized to a known laboratory standard of chemical analysis of carcasses.

Fat distribution and insulin response in prepubertal African American and white children.

Ethnic differences in obesity-related disease prevalence may relate to differences in fat distribution or metabolism. We conducted a study in 73 African American and white children to examine the relation between fat distribution and insulin and to determine whether ethnic differences in fat distribution or in adiposity-insulin relations contribute to differences in insulin concentrations. Fasting and postchallenge insulin concentrations were determined by oral-glucose-tolerance test, total body fat by dual-energy X-ray absorptiometry, and subcutaneous abdominal (SAAT) and intraabdominal (IAAT) adipose tissue by computerized tomography. African Americans had greater fasting insulin (x +/- SD: 79 +/- 37 compared with 55 +/- 23 pmol/L, P < 0.01), incremental 30-min insulin (567 +/- 438 compared with 300 +/- 304 pmol/L, P < 0.001), and incremental area under the insulin curve (AUC; 262 +/- 209 compared with 164 +/- 156 pmol/L, P < 0.01). In multiple linear regression, fasting insulin was independently related to total fat within both ethnic groups (model R2 = 0.42 and 0.52 for African Americans and whites, respectively), incremental 30-min insulin to total fat and IAAT in whites only (model R2 = 0.71), and AUC to SAAT in African Americans only (model R2 = 0.49). Adjusting insulin indexes for adiposity did not eliminate the significant effect of ethnicity. In general, relations between adiposity and insulin were stronger in whites than in African Americans. African American children had higher insulin concentrations than white children after total body fat, IAAT, and SAAT were controlled for. However, strong relations between adiposity (total and abdominal) and insulin in both groups suggest that obesity may contribute to disease risk regardless of ethnicity.

Visceral fat in white and African American prepubertal children.

The objectives of this study were 1) to examine interrelations among intraabdominal adipose tissue (IAAT) and other adiposity indexes, 2) to identify a visceral obesity index that is independent of total adiposity, and 3) to examine sex and ethnic (white compared with African American) differences in IAAT. We measured IAAT and subcutaneous abdominal adipose tissue (SAAT) using computed tomography, and total fat mass (FM) by dual-energy X-ray absorptiometry in a heterogenous sample of 101 children aged 7.7 +/- 1.6 y weighing 33.2 +/- 12.6 kg. IAAT was highly variable (mean +/- SE; 31 +/- 22 cm2; range: 7-107 cm2) and related to SAAT (r = 0.87) and FM (r = 0.81). The regression slope between IAAT and SAAT was significantly lower in African Americans (0.17 +/- 0.02 cm2 IATT/cm2 SAAT) than in whites (0.23 +/- 0.02 cm2 IAAT/cm2 SAAT). Within each ethnic group there was no effect of sex on IAAT adjusted for SAAT (mean +/- SE: 40.2 +/- 3.1 and 43.2 +/- 2.7 cm2 in white boys and girls, respectively; 26.4 +/- 1.9 and 25.1 +/- 1.6 cm2 in African American boys and girls, respectively). We conclude that in children 1) there is wide variation in visceral fatness; 2) IAAT relative to SAAT is an index of visceral fat, independent of FM, allowing examination of the unique effects of IAAT; and 3) the relative distribution of adipose tissue in the intraabdominal compared with the subcutaneous abdominal region is significantly lower in African Americans than in whites.

Influence of sex, seasonality, ethnicity, and geographic location on the components of total energy expenditure in young children: implications for energy requirements.

BACKGROUND: There are limited data on the influence of body composition, sex, seasonality, ethnicity, and geographic location on the components of energy expenditure in children. OBJECTIVE: The objective was to examine the determinants of total energy expenditure (TEE), resting energy expenditure (REE), and activity-related energy expenditure (AEE) in children. DESIGN: Cross-sectional data from 232 children (4-10 y of age) from 4 ethnic groups (white American, African American, Guatemalan Mestizo, and Native American Mohawk) were examined. RESULTS: In 104 white children studied in Vermont and Alabama, TEE was significantly higher in spring than in fall, higher in boys than in girls, and higher in children in Vermont (all effects: approximately 0.42 MJ/d, P < 0.05). The significant effect of sex was explained through REE; the influences of season and location were explained through AEE. In all children, there was no effect of sex but a significant effect of ethnicity (P < 0.01) on TEE: a significant effect of sex (P < 0.01) and no effect of ethnicity (P = 0.16) on REE; and no effect of sex and a significant effect of ethnicity on AEE. The significant effects of ethnicity were due to lower values in Guatemalan children. TEE correlated most strongly with weight (r = 0.81) and fat-free mass (r = 0.79-0.81); REE with weight (r = 0.85) and fat-free mass (r = 0.80-0.87); and AEE with maximal oxygen consumption (r = 0.54), fat-free mass (r = 0.50), and fat mass (r = 0.49). CONCLUSIONS: 1) Season and location influenced TEE in children through their effects on AEE, 2) a higher REE in boys was consistent across all groups examined, 3) Guatemalan children had lower TEE due to a lower AEE, 4) body weight may be the best predictor of TEE, and 5) maximal oxygen consumption was the strongest marker of AEE.

Do adaptive changes in metabolic rate favor weight regain in weight-reduced individuals? An examination of the set-point theory.

BACKGROUND: Obese persons generally regain lost weight, suggesting that adaptive metabolic changes favor return to a preset weight. OBJECTIVE: Our objective was to determine whether adaptive changes in resting metabolic rate (RMR) and thyroid hormones occur in weight-reduced persons, predisposing them to long-term weight gain. DESIGN: Twenty-four overweight, postmenopausal women were studied at a clinical research center in four 10-d study phases: the overweight state (phase 1, energy balance; phase 2, 3350 kJ/d) and after reduction to a normal-weight state (phase 3, 3350 kJ/d; phase 4, energy balance). Weight-reduced women were matched with 24 never-overweight control subjects. After each study phase, assessments included RMR (by indirect calorimetry), body composition (by hydrostatic weighing), serum triiodothyronine (T(3)), and reverse T(3) (rT(3)). Body weight was measured 4 y later, without intervention. RESULTS: Body composition-adjusted RMR and T(3):rT(3) fell during acute (phase 2) and chronic (phase 3) energy restriction (P: < 0.01), but returned to baseline in the normal-weight, energy-balanced state (phase 4; mean weight loss: 12.9 +/- 2.0 kg). RMR among weight-reduced women (4771 +/- 414 kJ/d) was not significantly different from that in control subjects (4955 +/- 414 kJ/d; P: = 0.14), and lower RMR did not predict greater 4-y weight regain (r = 0.27, NS). CONCLUSIONS: Energy restriction produces a transient hypothyroid-hypometabolic state that normalizes on return to energy-balanced conditions. Failure to establish energy balance after weight loss gives the misleading impression that weight-reduced persons are energy conservative and predisposed to weight regain. Our findings do not provide evidence in support of adaptive metabolic changes as an explanation for the tendency of weight-reduced persons to regain weight.

Longitudinal changes in fatness in white children: no effect of childhood energy expenditure.

Reduced energy expenditure may predispose children to the development of obesity, but there are limited longitudinal studies to support this theory. We studied 75 white, preadolescent children over 4 y by taking annual measures of body composition and resting energy expenditure (by indirect calorimetry) and two annual measures of total energy expenditure and physical-activity-related energy expenditure (by doubly labeled water). Body composition of parents was assessed at the onset of the study with use of underwater weighing. The major outcome variable was the individual rate of change in fat mass (FM) adjusted for fat-free mass (FFM). The influence of sex, energy expenditure components, initial FM, and parental FM on the rate of change in FM was analyzed by hierarchical linear modeling and analysis of variance. The rate of change in absolute FM was 0.89 +/- 1.08 kg/y (range: -0.44 to 5.6 kg/y). The rate of change in FM adjusted for FFM was 0.08 +/- 0.64 kg/y (range: -1.45 to 2.22 kg/y) and was similar among children of two nonobese parents and children with one nonobese or one obese parent, but was significantly higher in children with two obese parents (0.61 +/- 0.87 kg/y). The major determinants of change in FM adjusted for FFM were sex (greater fat gain in girls), initial fatness, and parental fatness. None of the components of energy expenditure were inversely related to change in FM. The main predictors of change in FM relative to FFM during preadolescent growth are sex, initial fatness, and parental fatness, but not reduced energy expenditure.

Corticosterone facilitates saccharin intake in adrenalectomized rats: does corticosterone increase stimulus salience?

Unlike normal rats, adrenalectomized rats do not voluntarily drink sweet saccharin solutions. To test whether this is a function of corticosterone in the circulation, and if corticosterone also increases the impetus for drinking saccharin after a period of withdrawal, we performed the following experiments. Young male rats were sham adrenalectomized (sham) or adrenalectomized (ADX); the ADX rats were provided with subcutaneous pellets containing (percent replacement of corticosterone, %B) 0%B, 15%B, 30%B or 100%B. Sham and ADX rats were immediately provided with saline (0.5%) and saccharin (2 mM) bottles in their home cages. Saccharin was allowed for 4 days on, 3 days off, 4 days on, 3 days off and a final day on, over the 15 days experiment. The dose of corticosterone determined both how much saccharin was voluntarily drunk by the ADX rats and the degree of overshoot after days off. Corticosterone also determined energy balance of the groups of ADX rats. The 30%B pellets restored food intake, body weight gain, insulin and caloric efficiency to the normal levels observed in sham rats. White fat depot weights and uncoupling protein concentration in brown adipose tissue were restored to sham levels by 100%B, suggesting that these variables which depend on activity in the sympathetic nervous system require considerable glucocorticoid receptor occupancy. We conclude that corticosterone increases the willingness to ingest sweetened water in a unimodal, dose-related manner, while moderate doses of corticosterone restore energy balance.

Voluntary sucrose ingestion, like corticosterone replacement, prevents the metabolic deficits of adrenalectomy.

We tested whether corticosterone replacement causes increased sucrose drinking in adrenalectomized (ADX) rats compared to sham-ADX (sham) rats. ADX rats given high doses of corticosterone drank as much sucrose as sham rats, whereas at three lower doses of corticosterone, drinking was similar between groups and was only approximately 40% of that ingested by shams. Compared to sham rats, ADX rats drinking saline, or saline and saccharin, gain weight more slowly, contain less white adipose tissue, and have higher sympathetic outflow as assessed by uncoupling protein content in brown adipose tissue. Allowing sucrose as well as saline to drink restored all of these variables to normal in ADX rats with no- or low-corticosterone. All endpoints from sucrose-drinking ADX rats with no-or low-corticosterone were indistinguishable from those in water-drinking shams. By contrast, sucrose-drinking ADX rats that were given high doses of corticosterone exhibited the usual catabolic effects of corticosterone on body weight gain and, unlike sucrose-drinking shams, were obese. We conclude that (i) high corticosterone stimulates the potability of sucrose and inhibits sympathetic stimulation of uncoupling protein; (ii) sucrose, without corticosterone, normalizes metabolic deficits in ADX rats probably through actions mediated both peripherally and by the central nervous system; and (iii) ADX rats have a distinct sucrose appetite.

Determinants of basal fat oxidation in healthy Caucasians.

In a retrospective study, we examined several determinants of basal fat oxidation in 720 healthy Caucasian volunteers. Adult men (n = 427) and women (n = 293) were characterized for resting energy expenditure and substrate oxidation by indirect calorimetry (after a 12-h overnight fast), peak O2 consumption by a treadmill test to exhaustion, body composition by hydrodensitometry, food intake from a 3-day food diary, and hormonal status by fasting hormone concentrations. Fat oxidation was negatively correlated with fat mass in men (r = -0.11; P < 0.05), but no statistical relationship was found in women. In a stepwise multiple regression analysis, fat oxidation was best predicted by peak O2 consumption and fat-free mass in men (model R2 = 0.142) and by free thyroxine, fat-free mass, and fasting insulin in women (model R2 = 0.153). Relative rates of fat oxidation (fat oxidation adjusted for differences in resting energy expenditure) were not correlated with fat mass in either gender. Women showed a lower rate of basal fat oxidation (both absolute and adjusted) than did men. Our results show that fat oxidation is not greater in individuals with a greater fat mass. Furthermore, our results support a sexual dimorphism in basal rates of fat oxidation.

Validation of quantitative magnetic resonance (QMR) for determination of body composition in rats.

OBJECTIVE: To validate the use of quantitative magnetic resonance (QMR) to measure fat and lean mass in conscious rats. METHODS: Fifty Osborne-Mendel rats (249-770 g) were scanned using the Echo Medical 2 MHz body composition analyzer. Each rat was scanned under six settings (three acquisition times, with and without determination of total water). Precision was determined by the calculated coefficient of variation (CV) of three consecutive scans. Accuracy was determined by comparing the first scan to chemical carcass analysis and analyzed by paired t-tests and least-squares regression analyses. Twenty-five rats were used in the validation study, and 25 in the cross-validation study. RESULTS: The precision for fat, lean and water at all settings was <1%. QMR significantly overestimated fat (~5%; P<0.0001), and underestimated both lean (~12.5%; P<0.0001) and total water (~5.5%; P<0.0001). All QMR measures were significantly correlated with carcass measures (r(2)>0.99; P<0.0001). Using prediction equations from the validation study with the cross-validation rats, there were no significant differences between QMR fat and carcass fat at any setting (P>0.400). For four of the six QMR settings, there were no significant differences between QMR and carcass lean (P>0.05). For total water, all QMR settings were significantly different than carcass (P<0.05), but only by ~1%. CONCLUSIONS: QMR showed excellent precision for the determination of fat, lean and water. Despite overestimating fat and underestimating lean and water, all were highly related to carcass values. When tested in the cross-validation group, QMR fat could be accurately predicted at all settings; however, lean mass (two settings) and water were still slightly different (less than 1%).