Negligible senescence in naked mole rats may be a consequence of well-maintained splicing regulation.

Naked mole-rats (NMRs) have amongst the longest lifespans relative to body size of any known, non-volant mammalian species. They also display an enhanced stress resistance phenotype, negligible senescence and very rarely are they burdened with chronic age-related diseases. Alternative splicing (AS) dysregulation is emerging as a potential driver of senescence and ageing. We hypothesised that the expression of splicing factors, important regulators of patterns of AS, may differ in NMRs when compared to other species with relatively shorter lifespans. We designed assays specific to NMR splicing regulatory factors and also to a panel of pre-selected brain-expressed genes known to demonstrate senescence-related alterations in AS in other species, and measured age-related changes in the transcript expression levels of these using embryonic and neonatal developmental stages through to extreme old age in NMR brain samples. We also compared splicing factor expression in both young mouse and NMR spleen and brain samples. Both NMR tissues showed approximately double the expression levels observed in tissues from similarly sized mice. Furthermore, contrary to observations in other species, following a brief period of labile expression in early life stages, adult NMR splicing factors and patterns of AS for functionally relevant brain genes remained remarkably stable for at least two decades. These findings are consistent with a model whereby the conservation of splicing regulation and stable patterns of AS may contribute to better molecular stress responses and the avoidance of senescence in NMRs, contributing to their exceptional lifespan and prolonged healthspan.

A stereotaxic atlas of the brain of the naked mole-rat (Heterocephalus glaber).

The naked mole-rat (Rodentia, Bathyergidae: Heterocephalus glaber) is a strictly subterranean eusocial mammal. These rodents show a suite of morphological and physiological adaptations, including brain specializations, to this underground milieu that they have inhabited since the early Miocene. Recently, naked mole-rats have received considerable attention as the longest living rodent known, and some of these brain specializations may be potentially important to their exceptional longevity. To serve as a basis for future brain studies, we have constructed a stereotaxic atlas of the brain of this species, labeling all major brain structures.

Bone mineralization and turnover in preterm infants at 8-12 years of age: the effect of early diet.

Our previous studies raised two hypotheses: first that suboptimal early nutrition and second that human milk have enhancing effects on long-term bone mineralization. To test these hypotheses experimentally, we measured whole body and regional bone mineral content (BMC) and bone mineral density (BMD), using dual-energy X-ray absorptiometry and single-photon absorptiometry, and bone turnover at 8-12 years in 244 preterm children (128 boys) who participated in a prospective randomized study of diet during the neonatal period. Dietary randomizations studied were: banked human milk (BBM, n = 87) versus preterm formula (PTF, n = 96) as the sole diet or as a supplement to mother's expressed breast milk (EBM); PTF (n = 25) versus term formula (TF, n = 36) as sole diet. Ninety-five term children of the same age were also studied. First, preterm children were shorter and lighter than term children (height SD scores -0.49 (1.1) vs. +0.22 (0.9), weight SD scores -0.41 (1.2) vs. +0.38 (1.0)) and had significantly lower whole-body BMC than their peers; decrements were also evident at some regional sites. These differences disappeared after adjusting for bone area, body size, and pubertal status. Second, children previously randomized to BBM versus PTF or TF versus PTF showed no significant differences in anthropometry, BMC, BMD, or osteocalcin (OC). Third, there was no independent effect of the proportion of EBM on BMC, BMD, or OC and no interaction between randomized diet and the amount of EBM received. Fourth, plasma OC was significantly higher in preterm children than in term children (12.4 vs. 11.0 ng/ml, p < 0.005) and in preterm children who had received a low-nutrient (BBM/TF) as opposed to a high-nutrient diet (PTF) during the neonatal period (12. 9 vs. 11.9 ng/ml, p = 0.03). In conclusion, preterm children are shorter, lighter, and have lower bone mass than their peers at age 8-12 years. The lower BMC is, however, appropriate for the bone and body size achieved. Despite large differences in early mineral intake, early diet does not affect bone mass in preterm children, and fresh human milk has no specific effect. However, poor nutrition during the neonatal period may result in higher bone formation rates during childhood.

Biochemical markers of calcium and bone metabolism during 18 months of lactation in Gambian women accustomed to a low calcium intake and in those consuming a calcium supplement.

The effect of 18 months of lactation on indexes of calcium and bone metabolism was studied in 60 Gambian women accustomed to a very low calcium intake. Half the women consumed a calcium supplement from 10 days postpartum for 52 weeks (supplement, 714 mg Ca/day; total Ca intake, 992 +/- 114 mg/day), and half consumed placebo (total Ca intake, 288 +/- 128 mg/day). Fasting blood and 24-h urine samples were collected at 1.5, 13, 52, and 78 weeks of lactation and analyzed for calciotropic hormones (intact PTH, 1,25-dihydroxyvitamin D, and calcitonin), bone turnover markers (osteocalcin, bone alkaline phosphatase, and urinary deoxypyridinoline), and plasma minerals (calcium and phosphate). The first months of lactation were associated with increased bone turnover and plasma phosphate, and decreased PTH and 1,25-dihydroxyvitamin D. These effects diminished by 52 weeks, although breast milk volumes remained high. The Gambians had higher PTH, 1,25-dihydroxyvitamin D, and bone formation than British women with a greater customary calcium intake. None of the biochemical indexes was affected by calcium supplementation, with the possible exception of bone alkaline phosphatase (-29% at 52 weeks; P = 0.015). These data demonstrate that lactation-associated changes in calcium and bone metabolism are physiological and are independent of dietary calcium supply in women with very low calcium intakes.

Restricted energy intake affects nocturnal body temperature and sleep patterns.

Changes in nocturnal body temperature, sleep patterns, and blood variables with energy restriction (3347 kJ/d) were studied in nine overweight (body mass index 26.1 +/- 2.8) premenopausal women aged 20-36 y. Variables were measured both 2 wk before and in the final 2 wk of 4-wk dieting. Data collected 28 d apart were compared to attenuate menstrual cycle differences. Subjects lost 8 +/- 4% of their initial body mass after 4 wk of energy restriction and plasma triiodothyronine (T3) was significantly reduced from 5.9 +/- 0.7 to 5.1 +/- 0.6 pmol/L (P < 0.05). The implied suppression of heat production (metabolic rate) with reduced T3 may account for the observed decrease in minimum nocturnal rectal temperature (from 36.5 +/- 0.3 to 36.3 +/- 0.3 degree C, P < 0.05). Furthermore, dieting significantly altered sleep patterns; sleep onset latency was lengthened and slow-wave sleep decreased (P < 0.05). These changes may be indicative of reduced restorative/biosynthetic requirements. It thus appears that energy restriction results in a hypometabolic state that affects nocturnal body temperature and sleep patterns.

Calcium metabolism and bone mass in female rabbits during skeletal maturation: effects of dietary calcium intake.

This study documents growth and dual-energy X-ray absorptiometry (DXA)-determined peak bone mass profiles in the rabbit model, and tests the hypothesis that rabbits show patterns of bone accretion similar to humans and thus may serve as a viable model for human bone physiology. It is also shown that dietary Ca intake affects peak bone mass and the temporal pattern of its attainment. Groups of weaned animals were administered two nutritionally complete but calcium-altered diets (0.5% or 1.0% Ca). We evaluated growth, bone mass accretion, and Ca metabolism from 20 to 56 weeks of age in both the 1.0% Ca and 0.5% Ca groups of rabbits. For each monthly period, we monitored body mass, naso-tail length, food consumption, and fecal output. In addition, we collected blood and 24 h urine samples for biochemical analyses, and measured bone mass variables of the lumbar spine with DXA. The 1.0% Ca group had a lower apparent fractional absorption of Ca and higher urinary Ca excretion, but retained more Ca than the 0.5% Ca group during the growth phase. Furthermore, the 1.0% Ca group had lower parathyroid hormone (PTH) and bone biochemical marker concentrations throughout the study than the 0.5% Ca group. The lower levels of PTH and bone markers of resorption and formation, may have resulted in a reduction in skeletal remodeling, and this physiological mechanism may have contributed to the 10% increase in peak bone mineral density of the lumbar spine in the 1.0% Ca group of rabbits.

Cholecalciferol has no effect on calcium and inorganic phosphorus balance in a naturally cholecalciferol-deplete subterranean mammal, the naked mole rat (Heterocephalus glaber).

Naked mole rats, Heterocephalus glaber, have no obvious source of cholecalciferol (D3) available to them, given their underground habitat and tubiferous diet. They have undetectable levels of 25-OH-D3 and as such appear to be naturally deplete in D3. The effect of an oral D3 supplement on mineral balance and homeostasis was therefore investigated. This D3 treatment did not affect circulating levels of Ca2+ and inorganic phosphorus (P(i]. Nor did D3 treatment affect mineral intake and absorption. The Ca2+ and P(i) present in the food was efficiently extracted and absorbed, resulting in an apparent fractional absorption (AFA) efficiency exceeding 98%. Irrespective of D3 treatment, the amount of Ca2+ and P(i) absorbed was positively correlated with the amount ingested, suggesting that intestinal uptake is by a passive D3-independent process. After D3 supplementation urinary Ca2+ secretion was unchanged; however, the amount of P(i) excreted in the urine increased (P less than or equal to 0.05). This resulted in a concomitant decline in P(i) AFR (P less than or equal to 0.02 from 99.95 +/- 0.02% to 99.82 +/- 0.03%). Almost all the Ca2+ and P(i) in the glomerular filtrate were reabsorbed, facilitating AFR efficiencies that approach physiological maxima (greater than 99%). Changes in AFR efficiency with D3 supplementation are therefore of no biological significance. Net mineral flux of both elements, irrespective of D3 treatment, was positive. It is speculated that the ever-growing incisors of these animals act as mineral dumps and assist in the tight regulation of plasma Ca2+ and P(i). These data suggest that naked mole rats utilize mechanisms independent of D3 in regulating mineral homeostasis and are therefore well-adapted to an environment devoid of sunlight.

Vitamin D metabolism in the Damara mole-rat is altered by exposure to sunlight yet mineral metabolism is unaffected.

Vitamin D may be endogenously synthesized in the skin in the presence of sunlight or, alternatively, acquired from dietary sources. Cryptomys damarensis appear to have a naturally impoverished vitamin D status with low plasma concentrations of both 25-hydroxyvitamin D (25(OH)D; < 5 ng/ml) and 1,25-dihydroxyvitamin D (1,25(OH)2D; < 20 pg/ml). We attribute this to their underground habitat and herbivorous habits. We questioned whether these subterranean mammals could utilize sunlight-mediated pathways and therefore compared vitamin D metabolism and function when animals were (a) housed naturally (control), (b) given an oral vitamin D3 (D3) supplement (1 IU/g dry matter food eaten per day) and (c) exposed to 10 h of sunlight. Control animals exhibited a highly efficient apparent fractional absorption of both calcium (Ca) and inorganic phosphorus (Pi) (> 90%), passive mode of intestinal mineral uptake, yet tightly regulated serum ionized calcium (Ca2+). The ratio of 25(OH)D-1 alpha-hydroxylase (1-OHase) to 25(OH)D-24R-hydroxylase (24-OHase) activity in the kidney, corresponded with a state of vitamin D deficiency. Cryptomys damarensis responded to both oral D3 supplementation and sun exposure by an increase in plasma concentration of 1,25(OH)2D with a commensurate decline (P < 0.05) in 1-OHase activity, and a resulting decrease (P < 0.05) in the ratio of 1-OHase:24-OHase activity. Despite these changes, the intestinal mode of Ca uptake and plasma total Ca, Ca2+ and Pi remained unchanged with either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Vitamin D hydroxylases and their regulation in a naturally vitamin D-deficient subterranean mammal, the naked mole rat (Heterocephalus glaber).

The vitamin D hormone 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is generated by a series of hydroxylation steps in the liver and kidneys. We investigated whether naturally vitamin D-deficient subterranean mammals (naked mole rats, Heterocephalus glaber) employ the same enzymatic pathways, and whether these are regulated in a similar manner to that established for other mammals. Vitamin D3-25-hydroxylase in the liver and both 25-hydroxyvitamin D3-1-hydroxylase and 25-hydroxyvitamin D3-24 hydroxylase (1-OHase and 24-OHase) in the kidney were detectable in mole rats. As expected for vitamin D-deficient mammals, the 1-OHase activity predominated over the 24-OHase. After mole rats received a supraphysiological supplement of vitamin D3, 1-OHase activity was suppressed and 24-OHase activity was enhanced. Irrespective of vitamin D status, forskolin (a protein kinase A activator) and dibutyryl cyclic AMP did not alter the activity of either 1-OHase or 24-OHase. These findings suggest that the response of renal hydroxylases to parathyroid hormone was blunted. Phorbol esters, 12-O-tetradecanoylphorbol 13-acetate (TPA) and 1-oleoyl-2-acetylglycerol (OAG) (protein kinase C activators), suppressed 1-OHase activity. 24-OHase activity was induced by TPA but not by OAG. These effects were similar to those illicited by vitamin D3 supplementation but were additive in that they increased the responses shown in vitamin D-replete mole rats. These data confirm that naturally vitamin D-deficient mole rats can convert vitamin D3 to the hormone, 1,25(OH)2D3.(ABSTRACT TRUNCATED AT 250 WORDS)

Maternal vitamin D status has no effect on the ontogeny of calcium-binding proteins in the duodenum, kidney and cerebellum of fetal mice.

The effects of vitamin D3 deficiency on the ontogeny of calcium-binding proteins (CaBPs) and the vitamin D receptor in the duodenum, kidney and cerebellum of the mouse were examined. Maternal vitamin D status did not affect the time of appearance of the fetal 28 kDa CaBP (CaBP-D28k) in the cerebellum, kidney and duodenum, and the 9 kDa CaBP (CaBP-D9k) in the intestine and kidney. Vitamin D receptor was undetectable in all fetal tissues, regardless of maternal vitamin D status, at all stages of gestation examined. Thus it appears that maternal vitamin D status does not affect the ontogeny of CaBP-D9k or CaBP-D28k in the mouse fetus. The factors that influence the appearance of calbindins in the fetus are unclear.

Trophoblastic giant cells of the mouse placenta contain calbindin-D9k but not the vitamin D receptor.

The effects of vitamin D deficiency on the ontogeny of calcium-binding proteins (CaBPs) and the vitamin D receptor (VDR) in the placenta and yolk sac of the mouse were examined. Maternal vitamin D status did not affect the time of appearance of CaBP-D9k (9 kDa) in the yolk sac endoderm or trophoblastic giant cells (TGCs) of the placenta. VDRs were undetectable in TGCs and yolk sac endoderm, but were present in the intraplacental yolk sac. Since yolk sac endoderm and TGCs contain CaBP but not VDR, it is unlikely that CaBP synthesis and/or activity in these cells is controlled by vitamin D. The TGCs, therefore, may be involved in vitamin D-independent transplacental transfer of calcium.

Effect of oral cholecalciferol supplementation at physiological and supraphysiological doses in naturally vitamin D3-deficient subterranean damara mole rats (Cryptomys damarensis).

The damara mole rat, Cryptomys damarensis, is a strictly subterranean dwelling herbivorous rodent that in its natural habitat has no access to any obvious source of cholecalciferol (D3). We examined the effects of D3 supplementation, at physiological and supraphysiological doses, on calcium metabolism, plasma concentrations of calcium and alkaline phosphatase (ALP) and D3 metabolites. Animals not receiving a D3 supplement maintained normal plasma calcium concentrations. In addition, they exhibited a high apparent fractional mineral absorption efficiency (91%) and maintained a positive mineral flux. The serum concentration of 25-(OH)D3 was undetectable (less than 5 nmol/l) and that of 1,25-(OH)2D3 was 41 +/- 10 pmol/l. Supplementation at a physiological dose of D3 resulted in increased plasma concentrations of D3 metabolites, food intake, apparent fractional absorption efficiency and apparent fractional retention efficiency. Despite the 1.8-fold increase in food intake, body mass remained constant suggesting that the enhanced energy intake was dissipated in catabolic processes. Plasma calcium and ALP concentrations were not significantly altered with physiological doses of D3. The group given supraphysiological doses of D3 exhibited hypercalcaemia, increased creatinine concentrations and markedly increased ALP levels. These data indicate that a pathological response to D3 intoxication occurred and that hepatic and renal excretory functions were impaired. It appears, therefore, that these animals function optimally at the low concentrations of D3 metabolites found naturally. Supplementation at both physiological and supraphysiological doses of D3 may disadvantage the damara mole rat.

Subterranean mole-rats naturally have an impoverished calciol status, yet synthesize calciol metabolites and calbindins.

Mole-rats (Family Bathyergidae) have no obvious source of calciol. They live in an environment devoid of sunlight and consume a herbivorous diet. Calciol status, metabolism and expression were examined in six species of Bathyergids. Serum levels of calcidiol in all species were < 5 micrograms/l and those of calcitriol were low (18.0 +/- 11.0 (SD) ng/l, N = 57) when compared to other rodents. Within 72 h of injecting animals with tritium-labelled calciol, most of the labelled prohormone had been metabolized to more polar metabolites. Three times more tritium-labelled calcitriol (19.3 +/- 2.9%) was present than (24R)-hydroxycalcidiol (6.2 +/- 10%). The natural absence of detectable circulating concentrations of calcidiol and the threefold greater amount of calcitriol to (24R)-hydroxycalcidiol produced indicate that calciol naturally is in short supply. Calciol-dependent calbindins were absent in the duodenum. Calbindin-D28k was present in the Purkinje cells of the cerebellum and in some collecting ducts and proximal and distal convoluted tubules of the kidney. Calbindin-D9k also was present but was localized uniquely in the juxtaglomerular cells of the five southern African species. These data confirm that Bathyergid mole-rats naturally have an impoverished calciol status. Despite the presence of calbindins in renal tissues, the functional importance of this hormone in calbindin synthesis and other normal mole-rat physiology is not known.

Beneficial physiological and performance responses to a month of restricted energy intake in healthy overweight women.

Changes in mood, performance, cortisol, and physiological variables with a month-long energy restricting diet (3.347 MJ/day) were studied in nine overweight (mean mass 71.2 +/- 8 kg; body mass index 26.1 +/- 2.8 kg/m(2)), healthy premenopausal (age 20-36 years) women. Measurements were taken in the 2 weeks before the diet (baseline) and again in the final 2 weeks of the diet to attenuate menstrual cycle differences. A reduction in energy intake and concomitant weight loss (5.80 +/- 1.65 kg) were accompanied by a significant decline in systolic blood pressure (5.4%), heart rate (7.6%), and cortisol concentration (13.6%). Fatigue and vigour on the Profile of Mood States (POMS) questionnaire were adversely affected; however, subjective assessments of mood, concentration, temperature sensitivity, appetite, and sleep quality using visual analogue scales, were not significantly altered during the month-long period of energy restriction. Motor performance, as assessed by hand-eye coordination, improved with both a reduction in mean reaction time and improved accuracy in response to visual stimuli. The very low-energy diet appeared to be neither physiologically nor psychologically stressful. Beneficial effects were evident with a reduction in BMI, reduced risk of cardiovascular stress, improved motor performance, and a decline in physiological stress with dieting success.

Short-term effects of macronutrient preloads on appetite and energy intake in lean women.

This study investigated the relative satiating hierarchy of the four energy-providing macronutrients (fat, carbohydrate (CHO), protein, and alcohol) in lean women. On four separate occasions, the composition of an iso-energetic lunch preload was manipulated in 12 lean (BMI < 25 kg/m2) women. The four treatments comprised a 1-MJ baseline meal and drink (40% fat, 48% CHO, 12% protein) to which was covertly added: 1) + 1MJ protein; 2) + 1MJ alcohol; 3) + 1MJ CHO; and 4) + 1MJ fat. Prior to and at 30-min intervals, subjects completed 100-mm visual analogue scales rating subjective hunger and satiety. Ninety min following the preload, an ad lib. lunch meal was given (40% fat, 48% CHO, and 12% protein) and energy intake (EI) measured. Energy intake at the lunch meal was 2195 (880, SD) kJ, 2772 (1191, SD) kJ, 2502 (681, SD), kJ and 2558 (1050, SD) kJ for the protein, alcohol, CHO, and fat preloads, respectively. There was no significant difference between the pleasantness of the preloads (p > 0.05). Macronutrient composition had a significant effect on short-term hunger (F = 3.19; p < 0.05), subjects being less hungry after the protein preload. Subjects also had a lower energy intake after the protein preload (F = 3.11; p < 0.05). We conclude that only protein has a differential short-term satiating effect when incorporated iso-energetically and at a similar energy density into the diet.

Food intake and the menstrual cycle: a retrospective analysis, with implications for appetite research.

The biological regulation of appetite is currently an important topic in nutrition, since hyperphagia has been implicated as the prime cause of obesity. Cyclical fluctuations in food intake occur in women across the menstrual cycle, with a periovulatory nadir and a peak in the luteal phase. These alterations in food intake, in response to ovarian steroid hormone changes may be more than 2.5 MJ/day, with the mean reported changes shown in 19 separate studies of 1.0 MJ/day. Hormonal induced fluctuations in food intake could, therefore, contribute to energy imbalance and consequent weight gain. Further, in nutrition studies involving women subjects where the menstrual cycle phase is not controlled, hormonally induced changes in food selection and intake may mask the often considerably smaller changes in response to experimental variables in appetite research.

Energy content of the evening meal alters nocturnal body temperature but not sleep.

Meals of varying energy content and episodes of sleep influence body temperature. We compared the effect of an evening meal, varying from high-energy (11.91 +/- 0.86 MJ) to average (5.74 +/- 0.88 MJ) and a 10-h fast (no evening meal), on nocturnal body temperature and sleep. Seven healthy men (20-24 years, mean body mass index of 23.4 +/- 2.6 kg/m2) reported to the laboratory for an evening meal at 2000 h having consumed similar amounts of food before 1300 h. After completing the meal, subjective hunger ratings were assessed, and a venous blood sample taken. The subjects spent 4 nonconsecutive nights (an adaptation night, followed by either of the two meal conditions or the fast in random order) in the sleep laboratory when polysomnographic recordings were made from 2300 to 0700 h. Meal energy content and serum concentrations of insulin, triglyceride, and low-density lipoproteins (LDL) varied significantly. Lower rectal temperatures were measured during the fast than following the meals. Over the 8-h recording period, thermal response indices (TRI) varied with higher body temperatures following the higher energy meal. Similar rectal temperatures were attained by the end of the sleep periods. There were no significant differences in any of the subjective or objective sleep measures. The physiological responses associated with the transient dietary changes of an evening meal or a 10-h fast altered nocturnal body temperature but did not significantly affect sleep of good sleepers when sleep was initiated 2 to 3 h after finishing the meal.

Appetite dysfunction in obese males: evidence for role of hyperinsulinaemia in passive overconsumption with a high fat diet.

OBJECTIVE: To test the hypothesis that caloric and fat intake in a pre-load meal have no subsequent effects upon blood glucose and insulin concentrations, perceived hunger, subsequent food intake and appetite control in lean and obese men. DESIGN: Lean and obese men reported to the laboratory in the morning in a fasted state where they were subject to an eating test based on the pre-load-test meal paradigm, using a double-blind protocol. The breakfast pre-load was either a reduced caloric low-fat (LF) meal or an overfeeding high-fat (HF) meal. LF was 20% of each individual's average daily energy requirement (ADER) and comprised 60% carbohydrate, 27% protein, and 13% fat, whilst HF was adjusted to yield 55% of the ADER, and comprised 45% carbohydrate, 22% protein and 43% fat. The pre-loads on both trials were administered as one single mean, and were given in a random order. After 5(1/2) h, an ad libitum test-lunch was given to determine how much energy was consumed. Between the two meals, blood samples were collected and subjective hunger ratings were assessed hourly. These variables were measured at 30-min intervals for 75 min after the ad libitum meal. STUDY PARTICIPANTS: Twelve healthy men, six of whom were lean (BMI 22. 50+/-1.08 kg.m2) and six of whom were obese (BMI 39.05+/-11.63 kg. m2) were recruited. RESULTS: When given 55% of their ADER in a HF pre-load meal, the obese group consumed more energy (5426+/-1126 kJ; F1,20=11.45, P<0.01), than the lean group did (3473+/-1114 kJ), accounting for 45% of the ADER in that meal setting. However, no differences between lean and obese intake were noted at the test meal following a LF pre-load. The lean group exhibited a significant inverse correlation (r=0.628, P<0.05) between serum insulin concentration before eating the test meal and the amount of energy consumed at the test meal, while such a relationship was absent in the obese group. CONCLUSION: The obese males were unable to compensate for the caloric overloading when fed a HF (55% ADER) pre-load at a subsequent test meal, whereas a calorically reduced pre-load (20% ADER) produced similar intakes to the lean control group. The inverse relationship noted in the lean group between insulin levels before the test meal and the energy intake at that test meal suggests that insulin may play a role in the regulation of appetite - satiety mechanism in lean males. The absence of such a relationship in the obese may suggest the site for possible appetite dysfunction contributing to obesity. These results further suggest that when obese individuals consume a high-fat meal they are prone to passive overconsumption, whereas lean study participants appear to be more resistant to such a phenomenon.

Validation and application of dual-energy X-ray absorptiometry to measure bone mineral density in rabbit vertebrae.

The rabbit could be a superior animal model to use in bone physiology studies, for the rabbit does attain true skeletal maturity. However, there are neither normative bone mineral density (BMD) data on the rabbit nor are there any validation studies on the use of dual-energy X-ray absorptiometry (DXA) to measure spinal BMD in the rabbit. Therefore, our aim was twofold: first, to investigate whether DXA could be used precisely and accurately to determine the bone mineral content (BMC). bone area (BA). and BMD of the rabbit lumbar spine: Second. to evaluate the new generation fan-beam DXA (Hologic QDR-4500) with small animal software by comparing two DXA methodologies QDR-1000 and QDR-4500 with each other, as well as against volumetric bone density (VBMD) derived from Archimedes principle. As expected. there was a magnification error in the QDR-4500 (BMC, BA. and BMD increased by 52%. 38%. and 10%, respectively, when the vertebrae were positioned flat against the scanning table). With the magnification error kept constant (vertebrae positioned 10 cm above the scanning table to match the height in vivo). there were no differences among the mean BMC. BA. and BMD of the rabbit vertebrae (Ll-L7) in vivo and in vitro using the QDR-4500 (p > 0.05). BMC, BA, and BMD differed between QDR-1000 and QDR-4500 in vitro because of a magnification error when the vertebrae were flat on the table (p <0.0001). and, consequently. the machines did not correlate with one another (p > 0.05). However, the BMC, BA, and BMD of the two DXAs did significantly correlate with each other in vivo and in vitro when the magnification error was compensated for (r = 0.44 and 0.52. i2 = 0.45 and 0.63. and 12 = 0.41 and 0.60. respectively. p < 0.05-0.008). The BMC and BMD (in vivo and in vitro) of the rabbit vertebrae measured by QDR-4500 was significantly correlated with VMBD, ash weight, and mineral content (,2 = 0.67-0.90,j <0.01-0.0001). Therefore, the QDR-4500 can be used to yield precise and accurate measurements of the rabbit spine.

Thermoregulation in the Angolan free-tailed bat Mops condylurus: A small mammal that uses hot roosts.

The Angolan free-tailed bat (Mops condylurus) uses roosts that often exceed 40 degrees C, an ambient temperature (Ta) that is lethal to many microchiropterans. We measured the physiological responses of this species at Ta's from 15 degrees to 45 degrees C. Torpor was commonly employed during the day at the lower Ta, but the bats generally remained euthermic at night, with a mean body temperature (Tb) of 35.2 degrees C. Metabolic rate reflected the pattern of Tb, increasing with falling Ta at night but decreasing during the day. Metabolic rate and evaporative losses were lower in torpid than in euthermic bats. Body temperature increased at each Ta >35 degrees C and was 43 degrees C at Ta of 45 degrees C. At Ta of 40 degrees C bats increased dry thermal conductance and evaporative heat loss compared to lower Ta. At 45 degrees C dry thermal conductance was lower than at 40 degrees C and evaporative heat loss was 132% of metabolic heat production. At high Ta there was only a slight increase in metabolic rate despite the employment of evaporative cooling mechanisms and an increase in Tb. Collectively our results suggest that M. condylurus is well suited to tolerate high Ta, and this may enable it to exploit thermally challenging roost sites and to colonise habitats and exploit food sources where less stressful roosts are limiting.