Overproduction of agouti-protein did not affect cAMP level but increased steroidogenesis in adrenal glands under forskolin stimulation

Mutation Agouti yellow (Ay) in mice Ay/a results in overproduction of agouti protein (AP), adult onset of obesity, increased corticosterone responses to restrain stress as compared with a/a mice (absence of AP). The enhanced corticosterone response in restrained Ay/a-mice compared with restrained a/a-mice occurred in result of increased adrenal reactivity to ACTH. The purpose of this work was to investigate the influence of AP overproduction on adenylate cyclase (AC) activity and steroidogenesis in forskolin stimulated adrenal cells. To estimate obesity influence, these parameters were measured in young (3 weeks) and adult (15 weeks) animals. The data obtained demonstrated that AP overproduction and the obesity did not affect the AC activity. However, forskolin stimulated corticosterone production in Ay/a-mice was higher than in a/a-mice (in young--during 0.5 h, in adult--during 3 hrs of incubation). So AP overproduction and obesity affect the corticosterone production. We hypothesize that AP overproduction affects steroidogenesis gene expression: accelerates gene activation in ontogenesis and increases enzyme de novo synthesis during long-term stimulation in adults.     

Adrenalectomy and steroid treatment in obese (ob/ob) and diabetic (db/db) mice

Adrenalectomy in young obese (ob/ob) and the diabetic (db/db) mouse slowed body weight gain. Treatment of adrenalectomized ob/ob mice with cortisone or deoxycorticosterone acetate (DOCA) significantly increased weight gain in a dose-related manner. Cortisone had no effect on weight gain on lean mice and treatment with dehydroepiandrosterone sulfate was without effect on either ob/ob or lean mice. The increment in body weight of adrenalectomized ob/ob mice treated with corticosterone and DOCA was associated with an increase in body weight and an increase in food intake. When adrenalectomy was performed at twenty-three days of age (five days before weaning), animals carrying the (db/db) genotype remained lighter than their normal littermates. These data document the importance of the adrenal gland and its steroids for the development and maintenance of many features of the obese or diabetes mouse.     

Steroidogenesis in adrenal glands of young and adult female mice with hyperexpression of the Aguoti gene

Dominant mutation Agouti yellow (AY) leads to ectopic overexpression of the Agouti gene and yellow coat color in mice. Furthermore, the mutation Ay increased adrenal response to emotional stress. The study assessed whether pleiotropic effect of the mutation Ay on adrenals function was dependent on sex and age. 3- and 15-week old female C57B1/6J mice of two agouti-genotypes: Ay/a (ectopic Agouti-gene overexpression) and a/a (absence of Agouti-protein), were investigated. Cyclic AMP level (adenylate cyclase activity) and corticosterone production in adrenal isolated cells stimulated by ACTH and dibutyrul cAMP (db-cAMP) were measured. ACTH increased cAMP accumulation to the same extent in Ay/a- and a/a-mouse adrenal cells of both ages. The dibutyrul cAMP-induced corticosterone production was higher in Ay/a than in a/a-mouse adrenal cells of both ages. The ACTH-induced corticosterone production in 3-week- old Ay/a-m/CQ was lower and in 15-week old Ay/a-mice was higher than in a/a-mice of the respective ages. The ACTH- and db-cAMP-induced steroidogenesis was not changed in Ay/a-mice and decreased in a/a-mice with age. Thus, in females as well as in males, the mutation Agouti yellow did not affect adenylate cyclase activity, increased db-cAMP-induced corticosterone production and disturbed development of adrenal cortex.     

Swim training applied at early age is critical to adrenal medulla catecholamine content and to attenuate monosodium L-glutamate-obesity onset in mice

Exercise has been recommended as a remedy against a worldwide obesity epidemic; however, the onset of excessive weight gain is not fully understood, nor are the effects of exercise on body weight control. Activity deficits of the sympathetic nervous system, including the sympathoadrenal axis, have been suggested to contribute to high fat accumulation in obesity. In the present work, swim training was used to observe fat accumulation and adrenal catecholamine stocks in hypothalamic-obese mice produced by neonatal treatment with monosodium L-glutamate (MSG). MSG-treated and normal mice swam for 15 min/day, 3 days a week, from weaning up to 90 days old (EXE 21-90); from weaning up to 50 days old (EXE 21-50) and from 60 up to 90 days old (EXE 60-90). Sedentary MSG and normal mice (SED groups) did not exercise at all. Animals were sacrificed at 90 days of age. MSG treatment induced obesity, demonstrated by a 43.08% increase in epididymal fat pad weight; these adult obese mice presented 27.7% less catecholamine stocks in their adrenal glands than untreated mice (p<0.001). Exercise reduced fat accumulation and increased adrenal catecholamine content in EXE 21-90 groups. These effects were more pronounced in MSG-mice than in normal ones. Halting the exercise (EXE 21-50 groups) still changed fat accretion and catecholamine stocks; however, no effects were recorded in the EXE 60-90 groups. We conclude that metabolic changes imposed by early exercise, leading to an attenuation of MSG-hypothalamic obesity onset, are at least in part due to sympathoadrenal activity modulation.     

Fat Intake Affects Adiposity,Comorbidity Factors,and Energy Metabolism of Sprague‐Dawley Rats

Objective: Childhood obesity is an emerging health problem. This study assesses the effects of three levels of dietary fat (10%, 32%, and 45% measured by kilocalories) on weight gain, body composition, energy metabolism, and comorbidity factors in rats from weaning through maturation. Research Methods and Procedures: The role of dietary fat on the susceptibility to obesity was assessed by feeding diets containing three levels of dietary fat to rats from weaning through 7 months of age. Body composition was analyzed by DXA after 6 and 12 weeks of dietary treatment. Energy metabolism was measured by indirect calorimetry. Results: Energy intake, weight gain, fat mass, and plasma glucose, cholesterol, triglyceride, free fatty acid, leptin, and insulin levels increased dose‐dependently with increased dietary fat. No difference in absolute lean mass among the three groups was observed. Therefore, the differences in weight gain are accounted for primarily by increased fat accretion. Compared with rats that were relatively resistant to obesity when on a 45% fat diet, diet‐induced obesity‐prone rats were in positive energy balance and had an elevated respiratory quotient, indicating a switch in energy substrate use from fat to carbohydrate, which promotes body‐fat accretion. Discussion: Our data support the hypothesis that administration of increasing amount of dietary fat to very young rats enhances susceptibility to diet‐induced obesity and its comorbidities.     

Body Composition at 6 months of Life: Comparison Of Air Displacement Plethysmography and Dual‐Energy X‐Ray Absorptiometry

Body composition assessment during infancy is important because it is a critical period for obesity risk development, thus valid tools are needed to accurately, precisely, and quickly determine both fat and fat‐free mass. The purpose of this study was to compare body composition estimates using dual‐energy x‐ray absorptiometry (DXA) and air displacement plethysmography (ADP) at 6 months old. We assessed the agreement between whole body composition using DXA and ADP in 84 full‐term average‐for‐gestational‐age boys and girls using DXA (Lunar iDXA v11–30.062; Infant whole body analysis enCore 2007 software, GE, Fairfield, CT) and ADP (Infant Body Composition System v3.1.0, COSMED USA, Concord, CA). Although the correlations between DXA and ADP for %fat (r = 0.925), absolute fat mass (r = 0.969), and absolute fat‐free mass (r = 0.945) were all significant, body composition estimates by DXA were greater for both %fat (31.1 ± 3.6% vs. 26.7 ± 4.7%; P < 0.001) and absolute fat mass (2,284 ± 449 vs. 1,921 ± 492 g; P < 0.001), and lower for fat‐free mass (5,022 ± 532 vs. 5,188 ± 508 g; P < 0.001) vs. ADP. Inter‐method differences in %fat decreased with increasing adiposity and differences in fat‐free mass decreased with increasing infant age. Estimates of body composition determined by DXA and ADP at 6 months of age were highly correlated, but did differ significantly. Additional work is required to identify the technical basis for these rather large inter‐method differences in infant body composition.     

Repeating of emotional stress prevents development of melanocortin obesity and type 2 diabetes in the mice with the Agouti yellow mutation

Brain melanocortin system (MC-system) participates in regulation of energy homeostasis. Dominant mutation yellow of the Agouti gene leads to the hyperphagia, obesity and type 2 diabetes. Stress is known to inhibit food intake and body weight. The aim of the work was to study effects of repeating emotional stress on food intake and lipid-carbohydrate metabolism in Ay-mice. Male mice of C57B1/6J strain predisposed to the obesity (Ay/a-genotype) and normal (a/a-genotype) were used. In control group food intake, body weight and blood levels of insulin and leptin were increased in Ay/a-mice as compared to a/a-mice. Repeating emotional stress (30 min restraint 3 times a week for 5 weeks) did not alter food intake and indices of lipid-carbohydrate metabolism in a/a-mice and decreased food intake, body weight and blood levels of insulin and leptin in Ay/a-mice. Insulin and leptin blood levels were the same in Ay/a- and a/a-mice on 5 week of treatment. The stress increased basal and stress-induced concentrations of corticosterone to an equal degree in Ay/a- and a/a-mice. Thus, light repeating emotional stress hampered development of obesity and 2 type diabetes in the mice with the Agouti yellow mutation.     

Gender differences in fat patterning in children living in Ankara

Body composition is an excellent indicator for assessing obesity and nutritional status of both individuals and populations. Youth obesity has important health and social implications, because a large proportion of adult obesity has its origin in childhood. Numerous studies report that adverse levels of cardiovascular diseases risk factors are associated with adiposity in children. Concerning the Turkish population there is up to now only limited information with regard to adiposity in children. The aim of this study was therefore to determine the anthropometric and body composition characteristics and to investigate sex differences in fat patterning including fat distribution in a group of children living in Ankara. The present study evaluated the body composition of 332 boys and 269 girls aged between 8 and 11 years, attending public schools. It was carried out by a cross-sectional study and was focused on that anthropometric variables, which reflect body fat and fat-free mass. Anthropometric measurements including height, weight, triceps and subscapular skinfolds thickness were carried out on these children. The body mass index (BMI) was also calculated. The measurements were used to estimate the two-compartment model of body composition: fat-free mass (FFM) and body fat (BF) from skinfold equations. The mean fat percentage in boys is highest at 11 years (16.8%) and lowest at 10 years (15.6%). In girls these figures come to 18.2% and 17.1%, respectively. Girls of these age groups have a significantly larger percentage of body fat and skinfold thickness. At this young age there is therefore clear evidence of sexual dimorphism in fat patterning, as girls are showing a greater subcutaneous adiposity, which is mainly contributed by the triceps fat. The body fat (kg) increases in both sexes all over the investigated age groups. The Pearson correlation matrix showed a high significant relation between the anthropometric measurements (p < 0.01). The present study confirms the findings that sexual dimorphism of fat patterning in children is to be seen in the age of 8 - 11 years. It furthermore presents basic data of body composition, which could serve as reference data in other studies on the Turkish population.     

Effects of dehydroepiandrosterone on obesity and glucose-6-phosphate dehydrogenase activity in the lethal yellow mouse (strain 129/Sv-Ay/Aw)

We investigated the anti-obesity effects of the adrenal androgen, dehydroepiandrosterone (DHEA), on genetically predisposed obese lethal yellow mice (Ay/Aw). Secondly, we tested the hypothesis that DHEA promotes its anti-obesity effects by decreasing the activity of glucose-6-phosphate dehydrogenase (G6PDH). We subjected four genotype-sex combinations of yellow and agouti (control) mice to four dietary treatments and determined weight changes, food consumption, and G6PDH activity. Although G6PDH activities of yellow mice were considerably decreased in the 0.4% DHEA treatment group, they were elevated in the 0.0 and 0.1% DHEA treatment groups. In contrast, G6PDH activities of DHEA-treated control agouti mice remained relatively constant. These studies confirm that DHEA prevents the Ay gene from promoting excess fat deposition via some mechanism(s) other than reduced dietary intake. However, the overall absence of agreement between weight change (gain or loss) and G6PDH activity suggests that the anti-obesity activity of DHEA is not mediated via G6PDH. Since yellow obese (Ay/Aw) mice were found to be more susceptible to DHEA's effects than their agouti (Aw/Aw) littermates, Ay appears to induce an altered metabolism in Ay/Aw mice which is more susceptible to the effects of DHEA than the normal metabolism of Aw/Aw mice.     

Body composition in Division I football players

This study assessed body composition of Division I football players (n = 69) and compared the findings with previously reported data to ascertain whether the increase in player total body mass that has been observed over the past 10 years has been accompanied by an increase in body fat. Body composition was determined by hydrostatic weighing and the measurement of skinfold thicknesses. Total body mass, skinfold thicknesses, and body fat were greater in the current players than in players in studies conducted in the early 1980s and early 1990s. Body fat varied significantly across playing position, with the defensive backs, offensive backs, and receivers being the leanest and the offensive linemen and tight ends the most fat. There was no significant relationship between body composition and playing year or scholarship status, nor were any differences observed between ethnic groups. Of important clinical relevance was the finding that the linemen (offensive, defensive) and tight ends were on average greater than 25% body fat, the borderline for obesity in this age group. Much of this fat was deposited in the abdominal region, a significant finding when one considers the high correlation between abdominal obesity and ischemic heart disease and stroke. The current findings suggest that more attention needs to be given to the nature of the increase in body mass being achieved by today's football player to minimize long-term negative health consequences, and the findings reemphasize the need identified in earlier studies of the importance of detraining programs for these athletes.     

Is genetically transmitted obesity due to an adipose tissue defect?

1. The aim of this investigation was to ascertain of a variety of obese rodents whether the primary cause of fat cell enlargement lay in the fat cell itself, or in its environment. Rodents studied were the mutant mice 'diabetic' (db/db), 'adipose' (dbad/dbad), and 'yellow obese' (Ay/+), New Zealand obese mice, CBA mice made obese with gold thioglucose, and obese BIO 4.24 hamsters. 2. Gonadal fat of obese or lean genotype was transplanted under the kidney capsule of an obese or lean host. Grafts were left in place for at least one month, then examined histologically to measure fat cell diameters, from which fat cell masses were calculated. 3. Immunological rejection of grafts was avoided either by using mice syngeneic except for the obesity producing mutation (db/db, dbad/dbad or Ay/+) or by transplanting into F1 hybrids (NZO X BALB/c) made by mating the strains acting as donors of obese or lean fat. Transplantation of fat between lean BIO 4.22 hamsters and obese BIO 4.24 hamsters was possible because these had common histocompatibility antigens. 4. In all the forms of murine obesity studied, 'lean' fat cells enlarged in an obese recipient to the size typical of cells in 'obese' fat whilst 'obese' fat cells shrunk in a lean recipient to, at least, the size typical of 'lean' fat. Lean hamster fat cells also enlarged in an 'obese' environment and 'obese' hamster cells shrunk in a 'lean' environment. 5. Environment therefore contributes to the determination of fat cell size in all the rodents studied, and in several rodents (db/db, dbad/dbad, Ay/+, and gold thioglucose obese mice) our results showed that environmental factors are of paramount importance in determining cell size, and factors associated with the fat cell itself make a negligible contribution.     

Reduced adiposity in ob/ob mice following total body irradiation and bone marrow transplantation

Objective: The objective of this study was to assess long‐term metabolic consequences of total body irradiation (TBI) and bone marrow transplantation. Severe obesity develops due to both hypertrophy and hyperplasia of adipocytes. We hypothesized that TBI would arrest adipose tissue growth and would affect insulin resistance (IR). Research Methods and Procedures: We exposed 2‐month‐old female ob/ob mice to 8 Grays of TBI followed by bone marrow transplantation and tested the animals for body weight (BW) gain, body composition, blood glucose, and insulin sensitivity. Results: Two months after TBI, irradiated mice stopped gaining BW, whereas non‐treated mice continued to grow. At the age of 9.5 months, body mass of irradiated mice was 60.6 ± 1.4 grams, which was only 61% of that in non‐treated ob/ob controls (99.4 ± 1.6 grams). Body composition measurements by DXA showed that decreased BW was primarily due to an impaired fat accumulation. This could not result from the production of leptin by bone marrow‐derived adipocyte progenitors because inhibition of the obese phenotype was identical in recipients of both B6 and ob/ob bone marrow. Inability of the irradiated mice to accumulate fat was associated with hepatomegaly, lower levels of monocyte chemoattractant protein‐1 expression in adipose tissue, and increased IR. Discussion: Our data argue in favor of the hypothesis that inability of adipose tissue to expand may increase IR. This mouse model may be valuable for studies of late‐onset radiation‐induced IR in humans.     

Prevention of caffeine-induced limb malformations by maternal adrenalectomy

Caffeine at high doses is a known rodent teratogen and induces limb malformations along with cleft palate in various strains of rats and mice. Fujii and Nishimura ('74) postulated that caffeine was teratogenic by virtue of catecholamine release from maternal or embryonic tissue. We tested this hypothesis by surgically removing the maternal adrenal gland on day 6 of pregnancy and then administering 175 mg/kg of caffeine intraperitoneally at 1600 h day 11 and 900 h day 12. The teratogenic effects of caffeine in adrenalectomized versus nonadrenalectomized AKR mice were assessed in day 18 fetuses. Thirty percent of the surviving offspring were malformed in caffeine-treated, nonadrenalectomized dams compared to 7% of the offspring from adrenalectomized dams. Therefore we believe caffeine teratogenesis is initiated by release of catecholamines from the maternal adrenal gland.     

A Low Sympathoadrenal Activity is Associated with Body Weight Gain and Development of Central Adiposity in Pima Indian Men

TATARANNI P ANTONIO JAMES B YOUNG, CLIFTON BOGARDUS, ERIC RAVUSSIN. A low sympathoadrenal activity is associated with body weight gain and development of central adiposity in Pima Indian men. To investigate the possible role of impaired sympathetic nervous system and/or adrenal medullary function in the etiology of human obesity, we studied 64 Pima Indian men (28 ± 6 years, 101 ± 25 kg, 34 ± 9% body fat, mean ± SD) in whom sympathoadrenal function was estimated at baseline by measurements of 24-hour urinary norepinephrine (NE) and epinephrine (Epi) excretion rates under weight-maintenance conditions. Body weight, body composition (hydrodensitometry), and body fat distribution (waist-to-thigh circumference ratio, W/T) were measured at baseline and follow-up. Follow-up data were available on 44 subjects who gained on average 8.4 ± 9.5 kg over 3.3 ± 2.1 years. In these subjects, baseline NE excretion rate, adjusted for its determinants (i.e., fat free mass, fat mass, and W/T), correlated negatively with bodyweight gain (r=?0.38; p=0.009). Baseline Epi excretion rate correlated negatively with changes in W/T (r=?0.44; p=0.003). In conclusion, our data show for the first time that a low sympathetic nervous system activity is associated with body weight gain in humans. Also, a low activity of the adrenal medulla is associated with the development of central adiposity.     

Adrenal medullary function and expression of catecholamine-synthesizing enzymes in mice with hypothalamic obesity

The mechanisms underlying the onset of obesity are complex and not completely understood. An imbalance of autonomic nervous system has been proposed to be a major cause of great fat deposits accumulation in hypothalamic obesity models. In this work we therefore investigated the adrenal chromaffin cells in monosodium glutamate (MSG)-treated obese female mice. Newborn mice were injected daily with MSG (4 mg/g body weight) or saline (controls) during the first five days of life and studied at 90 days of age. The adrenal catecholamine content was 56.0% lower in the obese group when compared to lean controls (P < 0.0001). Using isolated adrenal medulla we observed no difference in basal catecholamine secretion percentile between obese and lean animals. However, the percentile of catecholamine secretion stimulated by high K+ concentration was lower in the obese group. There was a decrease in the tyrosine hydroxylase enzyme expression (57.3%, P < 0.004) in adrenal glands of obese mice. Interestingly, the expression of dopamine beta-hydroxylase was also reduced (47.0%, P < 0.005). Phenylethanolamine N-methyltransferase expression was not affected. Our results show that in the MSG model, obesity status is associated with a defective adrenal chromaffin cell function. We conclude that in MSG obesity the low total catecholamine content is directly related to a decrease of key catecholamine-synthesizing enzymes, which by its turn may lead to a defective catecholamine secretion.     

Obesity in transgenic female mice with constitutively elevated luteinizing hormone secretion

Transgenic (TG) female mice, expressing a chimeric bovine luteinizing hormone (LH) beta-subunit/human chorionic gonadotropin beta-subunit COOH-terminal extension (bLHbeta-CTP) gene, produce high levels of circulating LH and serve as a model for functional ovarian hyperandrogenism and follicular cysts. We report here that obesity is a typical feature of these female mice. The mean body weight of the bLHbeta-CTP females was significantly higher than in controls at, and beyond 5 wk of age, and at 5 mo, it was 32% increased. At this age, the amount of white adipose tissue in the bLHbeta-CTP females was significantly increased, as reflected by the weight difference of the retroperitoneal fat pad. In addition, the expression of leptin mRNA in white adipose tissue of the TG females was elevated about twofold. Serum leptin and insulin levels, and food intake, were also increased significantly in the TG females. Brown adipose tissue (BAT) thermogenic activity, as measured by GDP binding to BAT mitochondria, was reduced (P < 0.05). Ovariectomy at the age of 3 wk totally prevented the development of obesity. In summary, the present results show that intact female bLHbeta-CTP mice are obese, have increased food consumption, and reduced BAT thermogenic activity. The weight gain can be explained partly by elevated androgens but is probably also contributed to the increased adrenal steroidogenesis. Hence, the bLHbeta-CTP mice provide a useful model for studying obesity related to elevated LH secretion, with consequent alterations in ovarian and adrenal function.     

Effect of adrenalectomy on the activity of small intestine enzymes in monosodium glutamate obese rats

It is well known that adrenalectomy (ADX) reverses the eating and energy balance disturbances in a variety of models of obesity associated with elevated food intake. We have previously demonstrated enhanced functional activity in the small intestine of neonatally monosodium glutamate-treated (MSG) obese rats despite the absence of overeating and we concluded that these changes might also contribute to the development of MSG obesity. The objective of the present experiments was to investigate whether ADX would affect the small intestinal functions and whether their changes would counteract attenuation or prevention of obesity development in MSG rats. Therefore the investigation was carried out in MSG-obese Wistar male rats and untreated intact rats adrenalectomized on day 40, as well as in lean littermates of MSG rats and intact rats subjected to Sham-ADX surgery. All animals had free access to a standard pellet diet after weaning. At the age of 80 days, body mass, body fat content and food consumption as well as changes of the brush-border-bound duodenal and jejunal alkaline phosphatase (AP), the dipeptidyl(amino)peptidase IV (DPP IV) and maltase activity were measured. During the postoperative period, ADX resulted in a significant decrease of mass gain in both MSG and control rats (P<0.05). ADX fully prevented the development of obesity in MSG rats (significantly decreased epididymal+retroperitoneal fat pad mass, P<0.05) and increased mean daily food intake (P<0.001). These effects were only minimal in the ADX controls suggesting that enhanced adrenal secretion is involved in the expression of MSG obesity and its complications. The AP activity in obese MSG rats was increased by about 21 % (P<0.01) in both intestinal segments when compared to the lean controls, whereas no parallel variations in the activities of DPP IV and maltase were observed in the intestinal parts mentioned. In MSG rats, ADX significantly reduced the AP activity in the duodenum and jejunum (P<0.01). A similar tendency was also seen in the DPP IV activity of adrenalectomized MSG rats as well as in lean control rats. Nevertheless, no significant effect of adrenal withdrawal on maltase activity was found. These results indicate that the decrease of enzyme activities in the small intestine and the different effectiveness of nutrient absorption might be a significant factor preventing the development of excess adiposity in glutamate-treated rats. This information contributes to a better understanding of the importance of small intestinal function for the development of obesity and its maintenance in later life.     

Perinatal Lead (Pb) Exposure Results in Sex-Specific Effects on Food Intake,Fat, Weight,and Insulin Response across the Murine Life-Course

Developmental lead (Pb) exposure has been associated with lower body weight in human infants and late onset obesity in mice. We determined the association of perinatal Pb exposure in mice with changes in obesity-related phenotypes into adulthood. Mice underwent exposure via maternal drinking water supplemented with 0 (control), 2.1 (low), 16 (medium), or 32 (high) ppm Pb-acetate two weeks prior to mating through lactation. Offspring were phenotyped at ages 3, 6, and 9 months for energy expenditure, spontaneous activity, food intake, body weight, body composition, and at age 10 months for glucose tolerance. Data analyses were stratified by sex and adjusted for litter effects. Exposed females and males exhibited increased energy expenditure as compared to controls (p<0.0001 for both). In females, horizontal activity differed significantly from controls (p = 0.02) over the life-course. Overall, food intake increased in exposed females and males (p<0.0008 and p<0.0001, respectively) with significant linear trends at 9 months in females (p = 0.01) and 6 months in males (p<0.01). Body weight was significantly increased in males at the medium and high exposures (p = 0.001 and p = 0.006). Total body fat differed among exposed females and males (p<0.0001 and p<0.0001, respectively). Insulin response was significantly increased in medium exposure males (p<0.05). Perinatal Pb exposure at blood lead levels between 4.1 µg/dL and 32 µg/dL is associated with increased food intake, body weight, total body fat, energy expenditure, activity, and insulin response in mice. Physiological effects of developmental Pb exposure persist and vary according to sex and age.     

Bayesian analyses of multiple epistatic QTL models for body weight and body composition in mice

To comprehensively investigate the genetic architecture of growth and obesity, we performed Bayesian analyses of multiple epistatic quantitative trait locus (QTL) models for body weights at five ages (12 days, 3, 6, 9 and 12 weeks) and body composition traits (weights of two fat pads and five organs) in mice produced from a cross of the F1 between M16i (selected for rapid growth rate) and CAST/Ei (wild-derived strain of small and lean mice) back to M16i. Bayesian model selection revealed a temporally regulated network of multiple QTL for body weight, involving both strong main effects and epistatic effects. No QTL had strong support for both early and late growth, although overlapping combinations of main and epistatic effects were observed at adjacent ages. Most main effects and epistatic interactions had an opposite effect on early and late growth. The contribution of epistasis was more pronounced for body weights at older ages. Body composition traits were also influenced by an interacting network of multiple QTLs. Several main and epistatic effects were shared by the body composition and body weight traits, suggesting that pleiotropy plays an important role in growth and obesity.     

Comparative studies of body mass,body measurements and organ weights of wild-derived and laboratory golden hamsters (Mesocricetus auratus)

All laboratory golden hamsters originate from a sibling pairing back in 1930. To investigate possible differences between domesticated and wild conspecifics, descendants of both strains were maintained under standardized laboratory conditions individually and in unisexual groups. Body mass and food consumption were monitored from birth to 22 weeks of age. The animals were subsequently sacrificed, and body measurements and body composition were analysed. In addition, the absolute and relative masses of different organs were measured. Laboratory hamsters gained more body mass through higher food consumption. However, they did not get fatter, since relative fat values were the same for both strains. Body measurements revealed only minor differences (in body and ear lengths). As deducible from the body mass, the organs (spleen, kidneys, adrenal glands, testes, epididymis and ovaries) were seen to be heavier in laboratory hamsters. Furthermore, with the exception of the kidneys, the same went for the relative values. There were distinct sexual specific differences in both strains only for body fat ( male symbol male symbol upward arrow ) and adrenal glands ( male symbol male symbol upward arrow ). In females, group housing induced an elevated level of aggression. In general, these housing conditions led to social stress symptoms, such as heavier adrenal glands. Additionally, spleen, kidneys, ovaries, body length and mass, body water and body fat were increased in group-housed hamsters. In conclusion, no major differences between laboratory and wild-derived hamsters were observed.