Biomedical subjects

G N Wade

Publications and source records attributed to G N Wade.

At least 19 recordsLinked to original sources

PubMed1992

Metabolic fuels and reproduction in female mammals.

A complete reproductive cycle of ovulation, conception, pregnancy, and lactation is one of the most energetically expensive activities that a female mammal can undertake. A reproductive attempt at a time when calories are not sufficiently available can result in a reduced return on the maternal energetic investment or even in the death of the mother and her offspring. Numerous physiological and behavioral mechanisms link reproduction and energy metabolism. Reproductive attempts may be interrupted or deferred when food is scarce or when other physiological processes, such as thermoregulation or fattening, make extraordinary energetic demands. Food deprivation suppresses both ovulation and estrous behavior. The neural mechanisms controlling pulsatile release of gonadotropin-releasing hormone (GnRH) and, consequently, luteinizing hormone secretion and ovarian function appear to respond to minute-to-minute changes in the availability of metabolic fuels. It is not clear whether GnRH-secreting neurons are able to detect the availability of metabolic fuels directly or whether this information is relayed from detectors elsewhere in the brain. Although pregnancy is less affected by fuel availability, both lactational performance and maternal behaviors are highly responsive to the energy supply. When a reproductive attempt is made, changes in hormone secretion have dramatic effects on the partitioning and utilization of metabolic fuels. During ovulatory cycles and pregnancy, the ovarian steroids, estradiol and progesterone, induce coordinated changes in the procurement, ingestion, metabolism, storage, and expenditure of metabolic fuels. Estradiol can act in the brain to alter regulatory behaviors, such as food intake and voluntary exercise, as well as adenohypophyseal and autonomic outputs. At the same time, ovarian hormones act on peripheral tissues such as adipose tissue, muscle, and liver to influence the metabolism, partitioning and storage of metabolic fuels. During lactation, the peptide hormones, prolactin and growth hormone, rather than estradiol and progesterone, are the principal hormones controlling partitioning and utilization of metabolic fuels. The interactions between metabolic fuels and reproduction are reciprocal, redundant, and ubiquitous; both behaviors and physiological processes play vital roles. Although there are species differences in the particular physiological and behavioral mechanisms mediating nutrition-reproduction interactions, two findings are consistent across species: 1) Reproductive physiology and behaviors are sensitive to the availability of oxidizable metabolic fuels. 2) When reproductive attempts are made, ovarian hormones play a major role in the changes in ingestion, partitioning, and utilization of metabolic fuels.

Animals↗

PubMed1992

Accelerated reproductive development in juvenile male ground squirrels fed a high-fat diet.

Male golden-mantled ground squirrels held at 23 degrees C were fed high-fat (HF) or standard (chow) diets. In December, ambient temperature was reduced to 6 degrees C, food was removed, and frequency and duration of torpor bouts were monitored continuously by radiotelemetry. Reproductive condition and body composition were assessed upon terminal arousal in the spring. Juvenile males fed the HF diet weighed more than chow-fed controls before and throughout the hibernation season and had significantly greater lipid masses at terminal arousal. Testes masses and plasma testosterone concentrations were substantially higher in HF than in chow-fed juveniles. The accelerated reproductive development of fatter squirrels was not contingent upon increases in the total number of days spent in torpor, number of torpor bouts, or the average duration of each arousal from torpor. Access to the HF diet had no effect on body mass, adiposity, or reproductive status of adult male ground squirrels in spring. Threshold levels of white adipose tissue and associated differences in availability of metabolic fuels may be permissive for testicular growth during the hibernation season. Juveniles exceed this threshold only when fed the HF diet.

Aging↗

PubMed1992

Expression of Fos-like proteins in gonadotropin-releasing hormone neurons of Syrian hamsters: effects of estrous cycles and metabolic fuels.

In female mammals, reproduction is sensitive to the availability of metabolic fuels, and food deprivation has been shown to suppress pulsatile LH secretion, attenuate the preovulatory LH surge, and prevent ovulation. It has been suggested that food deprivation impairs fertility by reducing the secretion of GnRH by GnRH-producing neurons in the forebrain. A series of experiments tested this hypothesis by examining the effects of estrous cycles and manipulations of metabolic fuel availability on the expression of Fos-like proteins (Fos-IR) in GnRH-immunoreactive (GnRH-IR) neurons in the forebrain of Syrian hamsters. GnRH-IR neurons were detected in several areas, including the diagonal band of Broca (DBB), medial septum (MS), rostral medial preoptic area (mPOA), and caudal POA. In the more rostral regions (DBB and MS/mPOA), GnRH-IR neurons expressed Fos-IR almost exclusively on day 4 of the cycle, just after the preovulatory LH surge. However, in the caudal POA, GnRH-IR neurons expressed Fos-IR across the entire cycle, including days 1-3, when LH secretion is pulsatile. Food deprivation on days 1 and 2 of the cycle, which attenuates the LH surge and blocks ovulation in hamsters, significantly reduced the proportion of GnRH-IR neurons that expressed Fos-IR on days 2 and 4 (caudal POA) or only on day 4 (DBB and MS/mPOA). Suppression of fuel availability with insulin or 2-deoxy-D-glucose on day 1 of the cycle mimicked the effects of food deprivation and reduced the proportion of caudal POA GnRH-IR neurons that expressed Fos-IR. The results of these experiments suggest that in Syrian hamsters, there are separate populations of GnRH-IR neurons associated with pulsatile and surge modes of LH secretion. In addition, the fact that manipulations of metabolic fuel availability cause changes in the expression of Fos-IR in both populations of GnRH-IR neurons provides strong support for the hypothesis that nutritional infertility is due in part to decreased GnRH secretion.

Animals↗

PubMed1991

Effects of ambient temperature and body fat content on maternal litter reduction in Syrian hamsters.

Reproduction in Syrian hamsters is sensitive to the general availability of metabolic energy. For example, females often modify their litter size by cannibalism on days 1-7 postpartum, and the number of young eaten is a function of the total supply of metabolic energy as determined by both food supply and body fat content. If the level of cannibalism is a function of energy availability, it might be expected that a drop in ambient temperature would increase cannibalism, since cold acclimation demands greater energy expenditure. We found that hamsters ate significantly more of their offspring when housed at 10 compared to 22 degrees C during lactation. The effect of cold on cannibalism was attenuated in hamsters fattened prior to cold exposure and exaggerated in hamsters that were lean prior to cold exposure. Thus, the litter size maintained by Syrian hamsters is a function of the total supply of metabolic fuels as determined by energy sources, such as food supply and adipose tissue, and by energetic costs of thermoregulatory and other processes.

Adipose Tissue↗

PubMed1991

Effects of ovariectomy on thermogenesis in brown adipose tissue and liver in Syrian hamsters.

Weight gain in ovariectomized Syrian hamsters occurs without increased food intake, which suggests that metabolic efficiency may be enhanced through a reduction in energy expenditure. We examined the effect of ovariectomy on metabolic activity in brown adipose tissue and liver. Four groups of hamsters (n = 13, each) were killed 0, 2, 4, or 16 weeks following ovariectomy. Ovariectomized hamsters rapidly gained weight without overeating. Body weights stabilized after 8 weeks and remained 12-17% above sham-operated control weights for the duration of the experiment. Weight gain in the hamsters ovariectomized for 16 weeks was characterized by significant increases in retroperitoneal white adipose tissue weight and carcass lipid content. Similar trends were seen in 2-week and 4-week ovariectomized animals. There were no differences in interscapular brown adipose tissue weight, protein content, DNA content, or norepinephrine (NE) content among sham-operated and 2-, 4-, or 16-week ovariectomized hamsters, indicating that ovariectomy had no effect on brown adipose tissue growth. Similarly, there was no difference in either sympathetic nervous system activity (estimated by the rate of NE turnover) or mitochondrial GDP binding among the four groups of hamsters. In contrast, hepatic cytochrome P-450 activity was significantly reduced 2, 4, and 16 weeks after ovariectomy. These results suggest that reduced thermogenic activity in liver, but not in brown adipose tissue, could contribute to the weight gain in Syrian hamsters after ovariectomy.

Adipose Tissue, Brown↗

PubMed1991

Insulin-induced anestrus in Syrian hamsters.

In Syrian hamsters, reproduction is sensitive to the availability of metabolic fuels. Estrous cycles can be interrupted by brief periods of food deprivation, by pharmacological inhibition of glycolysis and fatty acid oxidation, or by increasing energy demands for thermoregulation. We predicted that manipulations that divert an excessive portion of the metabolic fuel supply into storage also should inhibit reproduction. Redirection of metabolic fuels from oxidation to storage was accomplished by treatment with protamine zinc insulin suspension (PZI). Syrian hamsters treated with PZI and fed ad libitum increased their food intake by approximately equal to 40% and body fat stores, but there was no effect on estrous cycles. When PZI-treated hamsters were limited to approximately equal to 110% of their preinjection food intake, they still fattened, and there was a significant inhibition of estrous cyclicity. Thus, in the absence of overeating, PZI-enhanced energy storage may lead to a shortage of oxidizable metabolic fuels with the result that reproduction is inhibited in favor of processes essential for survival (e.g., cellular maintenance, thermoregulation). It is unlikely that insulin-induced anestrus is due to actions of PZI unrelated to metabolic fuel partitioning, because the hormone had no effects on estrous cyclicity in ad libitum-fed hamsters. These findings are inconsistent with the hypothesis that nutritional infertility is due to the failure to maintain a minimum body fat content and raise the possibility that the infertility associated with some types of obesity could be due in part to a disorder of macronutrient partitioning.

Anestrus↗

PubMed1991

Effects of pregnancy and ovarian steroids on fatty acid synthesis and uptake in Syrian hamsters.

The effects of pregnancy and ovarian steroids on the in vivo distribution of newly synthesized fatty acids (incorporation of tritium from 3H2O into fatty acid) in Syrian hamsters (Mesocricetus auratus) were examined. During late, but not early, gestation hamsters had reduced levels of newly synthesized fatty acids in heart, liver, uterus, and white adipose tissues (parametrial and inguinal fat pads). Treatment of ovariectomized hamsters with estradiol + progesterone significantly decreased fatty acid synthesis-uptake in heart, liver, and inguinal white adipose tissue. Treatment with either estradiol or progesterone alone was without significant effect in any tissue. Pretreatment of hamsters with Triton WR-1339 (tyloxapol), an inhibitor of lipoprotein lipase activity and tissue triglyceride uptake, abolished the effects of estradiol + progesterone in white adipose tissue and heart but not in liver. Thus hamsters lose body fat during pregnancy in part because of decreased de novo lipogenesis. The effect of pregnancy on lipogenesis is mimicked by treatment with estradiol + progesterone but not by either hormone alone. Furthermore, it appears that the liver is the principal site of estradiol + progesterone action on lipogenesis in Syrian hamsters.

Adipose Tissue↗

PubMed1991

Role of sympathetic nerves in effects of estradiol on rat white adipose tissue.

Two experiments examined the role of the sympathetic nerves in estradiol-induced fat pad weight losses in ovariectomized (OVX) rats. Rats were OVX, and the retroperitoneal white adipose tissue (RWAT) was unilaterally denervated 4 wk later. After 14 days of treatment with estradiol benzoate (EB, 2 micrograms/day), the intact pads lost 23% more weight than the denervated pads. There was no effect of denervation on fat pad weight or on cytosol estrogen receptor concentration in RWAT in the animals treated with sesame oil vehicle. These data suggest that the sympathetic nerves play a role in estrogen-induced reductions in fat pad weight but not via changes in adipose tissue cytosol estrogen receptors. A second experiment examined whether estradiol-induced fat pad weight losses are accompanied by increased norepinephrine (NE) turnover, an index of sympathetic activity, in adipose tissue. Rats were OVX and treated with EB or sesame oil vehicle. NE turnover was assessed by measuring the decline of tissue NE over time after injection of alpha-methyl-p-tyrosine, an inhibitor of tyrosine hydroxylase activity and thus NE biosynthesis. NE turnover in RWAT, but not heart, was significantly greater in animals treated with EB, suggesting that estradiol decreases fat pad weight in part by increasing sympathetic nervous system activity. It is possible that estradiol acts in the brain to regulate the activity of the sympathetic nerves to white adipose tissue and peripherally to alter adipose tissue responsiveness to catecholamines.

Adipose Tissue↗

PubMed1991

Effects of food restriction and social cues on sexual maturation and growth in male musk shrews (Suncus murinus).

In the first experiment, the effects of food availability on growth and reproduction were assessed by placing male musk shrews on 3 different feeding schedules, i.e. fed ad libitum, fed 50% of the amount eaten by the ad-libitum controls or fed 25% of the amount eaten by the ad-libitum controls. After 25 days, growth and sexual maturation were significantly retarded in both of the food-restricted groups compared to the control group. In the second experiment, the combined effects of food availability and social cues were investigated in juvenile males that were either fed ad libitum (during the day) or placed on a restricted diet known to inhibit growth and reproduction. Half of these males were either housed alone or with an adult female (separated from female during the day by a wire barrier, but in full contact at night). The ad-libitum-fed males living with a female ate more food, gained more body weight and were more sexually mature than ad-libitum-fed animals living alone. Furthermore, males in the two food-restricted groups had lower body weights and were sexually immature compared with males in both of the ad-libitum-fed groups. Finally, there were little or no differences in growth and reproduction between animals in the two food-restricted groups. These results suggest that food availability is an important environmental regulator of the timing of sexual maturation, and that stimulatory social cues cannot override the inhibitory effects of an inadequate diet.

Androgens↗

PubMed1990

Long day lengths enhance myelination of midbrain and hindbrain regions of developing meadow voles.

Rates of brain growth differed in meadow voles maintained in long (LP) or short (SP) photoperiods postnatally. At 35 days of age, brain weight was greater by 6.6% in LP males and by 4.7% in LP females as compared to their SP counterparts. Whole brain galactolipid content, an index of brain myelin, was greater by 15.6% in LP as compared to SP males. At 70 days of age, brains of LP males were 4% heavier than those of SP males. Differences attributable to photoperiod were most pronounced in midbrain and hindbrain (8% and 14%, respectively). DNA and galactolipid contents were greater by 11% and 15%, respectively, in hindbrain of LP males. Photoperiod did not affect any of these measures in diencephalon, striatum, or cerebellum. Short day lengths reduce myelination in meadow voles, presumably by decreasing proliferation rates of oligodendroglia. This is one facet of a general delay in somatic development associated with being born at the end of the normal breeding season when day lengths are decreasing or below a critical threshold.

Animals↗

PubMed1990

Long day lengths promote brain growth in meadow voles.

Male meadow voles kept in a long photoperiod (LP) from birth to 70 days of age have heavier brains than those kept in a short photoperiod (SP). Brain weights of male voles kept in the LP first exceeded those of SP animals at 20 days of age; differences were greatest at 35 days (5.8%) and persisted through 140 days of age (2%), although the magnitude of the difference declined progressively. Accelerated compensatory increases in brain weight were observed in voles transferred from the SP to the LP at 70 days of age. Total brain DNA content, an index of cell number, was not significantly affected by initial or final photoperiod, although it increased 7.8% within 70 days after voles were transferred from the SP to the LP. Brain weights (but not DNA content) of males exceeded those of females, but this sex difference was present only in the LP. We suggest that short day lengths retard brain development by reducing rates of myelination and possibly reducing cell size as well; this is part of a general retardation of somatic growth associated with a delayed onset of puberty that can be reversed by a stimulatory LP but, ordinarily, occurs spontaneously as voles become refractory to short day lengths.

Aging↗

PubMed1990

Sexual dimorphism in brain weight of meadow voles: role of gonadal hormones.

In most adult mammals, brain weights of males exceed those of females. The role of androgens in the genesis of this sex difference was assessed in meadow voles by acute neonatal or chronic postweaning manipulation of testosterone titers. Female voles given a single injection of testosterone propionate (TP) on the second day of postnatal life had brain weights in adulthood that were indistinguishable from those of male voles and significantly heavier than those of control females. Whole brain DNA content, a measure of cell number, was not increased by neonatal TP treatment. Females treated with TP from day 19 to 70 had lower brain weights than control females and males gonadectomized at 19 days of age had greater brain weights than did intact male voles at day 70. The sex dimorphism in brain weight reflects organizational effects of testosterone during perinatal development. Beginning at weaning, and continuing through postpubertal development, testosterone decreases brain weight in both sexes. We suggest that testosterone affects brain weight by altering cell size or non-cellular components rather than cell number.

Animals↗

PubMed1990

Decreased availability of metabolic fuels induces anestrus in golden hamsters.

Food deprivation inhibits ovulation and estrous behavior in golden hamsters. In experiment 1, the effects of phasic starvation (food deprivation on days 1 and 2 of the 4-day estrous cycle) depended on prior body weight and fat content. Starvation-induced anestrus, which occurs after only one cycle of phasic starvation in lean hamsters, did not occur until after three or more cycles in fat hamsters. None of the fat hamsters became anestrous until their body weights had declined to the level of lean hamsters. However, in experiment 2, we found evidence that changes in reproductive status were not signaled by any dimension of body size per se but instead by the general availability of metabolic fuels. Estrous cycles of thin hamsters were not significantly affected by food deprivation and weight loss when the hamsters were provided with either a 25% glucose solution or with vegetable shortening. In experiment 3, simultaneous pharmacological reduction of both fatty acid oxidation and glycolysis inhibited estrous cycles in hamsters fed ad libitum. Estradiol treatment restored estrous behavior, but not ovulation, in food-deprived, lean hamsters and in hamsters in which both fatty acid oxidation and glycolysis were reduced. Decreased availability of utilizable metabolic fuels may inhibit follicular development, which may in turn lead to circulating estradiol levels that are insufficient to stimulate estrous behavior.

Adipose Tissue↗

PubMed1990

Effects of diet and body fat content on cold-induced anestrus in Syrian hamsters.

Mammalian reproduction is inhibited by food shortages, increased foraging requirements, and other factors that decrease the energy available for biological processes. Cold-induced inhibition of reproduction may result from a depletion of available metabolic energy due to the increased requirements for thermogenesis or, alternatively, from mechanisms unrelated to energy expenditure. We examined the relationship between energy availability (in the diet and the body fat stores) and cold-induced anestrus in Syrian hamsters. In experiment 1, hamsters were housed in the cold (5 degrees C) and fed diets that differed in the amount of effort required to ingest them. The number of consecutive estrous cycles was positively correlated with caloric intake and negatively correlated with body weight loss in the cold. In experiment 2, hamsters were fed these diets for several weeks, so that they differed dramatically in body weight and fat content before cold exposure. Half of each group retained the same diet during cold exposure, whereas the other half were fed a regular chow diet. The effects of body weight before cold exposure were less pronounced than the effects of caloric intake during cold exposure. In experiment 3, females were fed different diets before cold exposure, then, during cold exposure, all were fed in a manner that decreased food intake and increased the effort required to obtain food. This energetic challenge exaggerated the effect of prior body weight on the latency to cold-induced anestrus. Thus the latency to cold-induced anestrus in Syrian hamsters is primarily a function of the availability of metabolic energy.(ABSTRACT TRUNCATED AT 250 WORDS)

Adipose Tissue↗

PubMed1989

Availability of metabolic fuels controls estrous cyclicity of Syrian hamsters.

Food deprivation and weight loss inhibit ovulation and estrous behavior in Syrian hamsters. In the present experiments, lean hamsters were more susceptible to starvation-induced anestrus than fat hamsters. However, anestrus was not caused by changes in any dimension of body size per se, but instead by the availability of metabolic fuels. Simultaneous pharmacological blockade of both fatty acid oxidation and glycolysis inhibited reproduction, but, as long as one of these metabolic pathways could be used, estrous cycles continued. Thus, reproduction in female Syrian hamsters is sensitive to the general availability of oxidizable metabolic fuels.

Animals↗

PubMed1989

Effects of maternal diet, body weight and body composition on infanticide in Syrian hamsters.

We examined the idea that female hamsters kill and eat their own offspring as part of an organized mechanism that balances litter size with metabolic energy supply. In Experiment 1, females fed diets that made them lighter and leaner cannibalized more offspring and maintained smaller litters than females fed diets that made them heavier and fatter. A greater supply of metabolic energy from the diet and/or from body fat stores may have attenuated cannibalism in heavier mothers. In Experiment 2, food restriction during lactation increased the level of cannibalism to a greater degree in lighter, leaner mothers. Heavier, fatter mothers may have eaten fewer offspring because they were better able to mobilize fatty acids from adipose tissue as an alternative fuel source during food restriction. These results suggest that an important factor influencing cannibalism of pups is the general availability of metabolic fuels from both external (food supply) and internal (adipose tissue) sources.

Animals↗

PubMed1989

Progesterone can either increase or decrease weight gain and adiposity in ovariectomized Syrian hamsters.

We examined the effects of estradiol and progesterone on weight gain, food intake, and carcass composition in Syrian hamsters (Mesocricetus auratus). In ovariectomized (OVX) hamsters injections of 5 micrograms/day estradiol benzoate (EB) alone decreased weight gain and adiposity, whereas treatment with progesterone alone (1 or 5 mg/day) resulted in increased weight gain and adiposity. However, concurrent treatment with progesterone and EB reduced body fat content to levels significantly below those of hamsters treated with EB alone. In a second experiment, 17 beta-estradiol and progesterone were administered via subcutaneous Silastic capsules in doses which produce physiological levels of steroids. Implants of estradiol significantly decreased body weight gain and fat content. As in the first experiment, these effects of estradiol were exaggerated by concurrent progesterone administration. Implants of progesterone alone did not affect body weight or fatness in OVX hamsters. These data indicate that estradiol and progesterone interact to decrease body lipid stores in hamsters, whereas in rats progesterone reverses the adiposity-reducing actions of estradiol. This species difference in responses to progesterone could help to explain why rats increase, whereas hamsters decrease, their body lipid stores during pregnancy, when circulating progesterone levels are elevated.

Adipose Tissue↗

PubMed1989

Effects of norepinephrine and denervation on brown adipose tissue in Syrian hamsters.

Daily injections of either 0.8 or 3.2 mg norepinephrine (NE)/kg for 2 wk failed to stimulate brown adipose tissue (BAT) growth, GDP binding, or cytochrome-c oxidase activity (COA) in Syrian hamsters (Mesocricetus auratus). However, a single injection of 1.6 mg NE/kg produced a small (23%) but significant acute increase in BAT GDP binding without affecting COA. Thus there is some loss of sensitivity to NE with chronic treatment in Syrian hamsters. Unilateral sympathectomy by surgical denervation of the interscapular BAT (IBAT) resulted in decreased GDP binding and COA in the denervated pad. Chronic NE treatment in hamsters with denervated IBAT only partially reversed the denervation-induced decreases in GDP binding and COA. It therefore appears that NE is not solely responsible for the maintenance and stimulation of thermogenic activity and COA in Syrian hamster BAT. Denervation of IBAT also resulted in elevated levels of lipoprotein lipase (LPL) in this tissue, a surprising finding since brown and white adipose tissue LPL activity were both stimulated by chronic NE treatment. Therefore, although NE has a stimulatory effect on LPL activity, the primary influence of the neural input to IBAT on this enzyme is inhibitory. These data exemplify dramatic differences between rats and hamsters in the mechanisms controlling BAT thermogenesis and white and brown adipose tissue LPL activity.

Adipose Tissue, Brown↗