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Biomedical subjects

G N Wade

Publications and source records attributed to G N Wade.

At least 73 records · Page 4Linked to original sources

Dissociation of sympathetic and thermogenic activity in brown fat of Syrian hamsters.

Syrian hamsters (Mesocricetus auratus) were fed a high-fat (HF) diet for up to 16 wk. Sympathetic and thermogenic activities in their brown adipose tissue (BAT) were assessed by measuring norepinephrine content and turnover and mitochondrial GDP binding and cytochrome c oxidase activity. Chronic ingestion of the HF diet resulted in significant increases in carcass lipid and interscapular BAT wet weight by the end of the second week. HF-fed hamsters were slightly hyperphagic during the first 2 wk of HF feeding only. Significant weight gains persisted beyond the period of hyperphagia. Hypertrophy of interscapular BAT after 16 wk on the HF diet was accompanied by increases in protein and DNA content, indicating growth of functional tissue. Norepinephrine turnover and content in BAT were decreased throughout the entire period of HF feeding, regardless of changes in caloric intake or body weight. Mitochondrial cytochrome c oxidase activity and GDP binding were increased after 16 wk on the HF diet, a time when the HF-fed animals were obese but not hyperphagic. These results demonstrate a dissociation of BAT thermogenesis from sympathetic activity in the tissue. It appears that sympathetic nervous system activity in BAT was suppressed by the HF diet, whereas thermogenic activity of the tissue was activated when the hamsters became obese.

Adipose Tissue, Brown↗

Energy balance and brown adipose tissue thermogenesis during pregnancy in Syrian hamsters.

Energy balance and brown adipose tissue thermogenesis were examined during pregnancy in Syrian hamsters (Mesocricetus auratus). Neither estrous cycles nor pregnancy had any effect on food intake, but both were accompanied by significant changes in body weight. Despite their substantial weight gains (attributable to growth of fetuses and placentas), pregnant hamsters actually lost a mean of 48 kJ in carcass energy, whereas unmated controls gained 98 kJ over the same 15 days. During pregnancy hamsters exhibited an increase in protein deposition (almost entirely in the fetuses and placentas), but they lost nearly 40% of their body lipid. An apparent increase in energy expenditure occurred despite a highly significant decrease in brown adipose tissue thermogenesis during pregnancy. By day 15 of pregnancy (within 13 h of expected parturition) there were substantial decreases in interscapular brown adipose tissue weight (-59%), protein content (-54%), and cytochrome-c oxidase activity (-69%). These changes in brown adipose tissue were evident by day 4 of pregnancy and persisted through lactation. It is suggested that this suppression of brown adipose tissue function is due to increased circulating levels of prolactin and subsequently to the nutritional stress of conceptus growth in the absence of an increase in food intake.

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Photoperiod and body weight in female Syrian hamsters: skeleton photoperiods, response magnitude, and development of photorefractoriness.

Two experiments examined the effects of various photoperiods on body weight and reproductive function in Syrian hamsters (Mesocricetus auratus). In Experiment 1 female hamsters were exposed to symmetrical skeleton photoperiods in which dawn and dusk were mimicked by 1-hr light pulses. A skeleton long (LD 16:8) photoperiod had no effect on body weight or estrous cyclicity (compared with animals in a complete LD 16:8 photoperiod), but exposure to a skeleton short (LD 10:14) photoperiod increased body weight and interrupted estrous cycles. Thus, body weight appears to respond to the relative timing of the two light pulses (a circadian mechanism) rather than to the absolute amount of light or darkness (an hourglass mechanism), just as does reproduction. In Experiment 2 female hamsters were exposed to a long photoperiod (LD 16:8) or to one of two short photoperiods (LD 10:14 and LD 8:16). Both short photoperiods increased body weight and interrupted estrous cycles, but the LD 8:16 photoperiod was substantially more effective at increasing body weight than was the LD 10:14. Thus, hamster body weight appears to be capable of a graded response to photoperiod, with shorter days producing a greater obesity. With prolonged exposure to the two short photoperiods (greater than 30 weeks), body weights spontaneously returned to the same level as the long-day controls, and estrous cycles resumed. When these hamsters were treated with the pineal gland hormone, melatonin, only those housed in long days exhibited the characteristic body weight gains, growth of brown and white adipose tissues, and decreases in uterine weight. Therefore, with prolonged exposure to short days, energy balance develops a photorefractoriness and an insensitivity to melatonin treatment, just as with reproductive function.

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The role of the uterus in regulation of heat duration in cycling rats.

These experiments examined the effects of hysterectomy on heat duration and on the reinduction of estrous behavior by progesterone (P) following the termination of spontaneous heat in 4-day cycling rats. Hysterectomy did not affect the onset of estrus but prolonged heat duration. The average duration of sexual receptivity for hysterectomized (H) and sham-hysterectomized (SH) rats was 18.2 and 13.0 hr, respectively. Furthermore, H animals injected with either 0.5 mg P within 2 hr, or 4.0 mg P 24 hr following the termination of natural estrus showed significantly higher lordosis and solicitation responses than SH rats similarly treated. These behavioral findings were correlated with the level of hypothalamic progestin receptors. That is, H animals had a significantly higher concentration of progestin receptors than SH rats immediately following the termination of spontaneous heat and also 24 hr later. Both in estrous-cycling rats and in gonadectomized animals treated with estradiol benzoate (EB), hysterectomy resulted in higher serum estradiol (E2) levels. The results of these experiments suggest that prolongation of the period of sexual receptivity and the facilitated behavioral responses to P following the cessation of estrus in hysterectomized animals may be due to a lowered clearance rate of circulating estradiol which presumably enhances the estrogen conditioning of the neural substrates.

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Body weight, food intake and energy regulation in exercising and melatonin-treated Siberian hamsters.

The coupling among energy intake, storage, and expenditure was examined in male Siberian hamsters (Phodopus sungorus sungorus) given access to running wheels for 14 weeks. Half of the hamsters were injected with melatonin in a schedule that mimics the effects of short photoperiods by decreasing body weight, carcass lipid content, and testis weight. The exercise-induced body weight increases which are seen in Syrian hamsters (Mesocricetus auratus) were not found in Siberian hamsters. Instead, the Siberian hamsters maintained their body weights, compensating for the increased energy demands of exercise by increasing their food intakes. Exercise did not affect carcass composition. Melatonin treatment decreased food intake and carcass lipid stores but did not affect voluntary exercise. The previously reported decrease in testis weight was seen in all melatonin-treated hamsters, but the stimulation of brown adipose tissue growth was not. Thus, exercising Siberian hamsters, unlike exercising Syrian hamsters, appear to exhibit a tight coupling among energy intake, storage, and expenditure.

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Photoperiodic control of seasonal body weight cycles in hamsters.

Syrian (Mesocricetus auratus) and Siberian (Phodopus sungorus sungorus) hamsters exhibit seasonal changes in body weight mainly by altering their carcass lipid stores. These seasonal changes are triggered largely by the photoperiod. Although both species exhibit gonadal regression when exposed to short photoperiods ("winterlike") daylength), they show opposite body weight changes. Syrian hamsters gain weight, but Siberian hamsters lose weight following short photoperiod exposure. Syrian hamsters prepare for overwintering by increasing energy stored as carcass lipid. In contrast, Siberian hamsters decrease their metabolic mass and therefore require lower energy intake for energy maintenance. In Syrian, and perhaps Siberian hamsters the short day-induced weight changes are exaggerated by high fat diets. Both species show photoperiod-induced changes in body weight without changing their food intake, suggesting a metabolic basis for these effects. In Syrian hamsters, the obesity is not secondary to gonadal regression, whereas in Siberian hamsters, the decrease in body weight is independent of the gonads for males but may be dependent upon the gonads in females. The pineal gland and its hormone, melatonin, are important transducers of photoperiodic signals in hamsters. This is certainly true for Siberian hamsters, in which pinealectomy blocks the short day-induced body weight loss. In contrast, pinealectomy has little effect on short day-induced weight gain in Syrian hamsters. Nevertheless, in both species, the body weight and gonadal changes induced by short day exposure are mimicked by systemic administration of melatonin in long day-housed animals. Thus, for these two hamster species, the same hormone, melatonin, produces opposite effects on body weight but does so by affecting the same carcass component. The target sites of action for the effects of melatonin on body weight change, energy metabolism, and reproductive status are not known. However, the suprachiasmatic and paraventricular nuclei of the hypothalamus are potentially important sites of action. The target site(s) and mechanism(s) of action for the pineal/melatonin-independent effect of photoperiod on body weight in Syrian hamsters are also unknown. This photoperiodic response is highly unusual among mammals in that it is not pineal-dependent. Studies of the mechanisms underlying these body weight changes in Syrian and Siberian hamsters may provide fundamental knowledge about how environmental influences affect obesity and they may also provide insight into the various strategies for overwintering shaped by natural selection.(ABSTRACT TRUNCATED AT 400 WORDS)

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Paraventricular nucleus lesions exaggerate dietary obesity but block photoperiod-induced weight gains and suspension of estrous cyclicity in Syrian hamsters.

Lesions of the paraventricular nucleus (PVN) of the hypothalamus block short photoperiod-induced testicular regression in Syrian hamsters. We examined the effects of PVN or sham lesions on the short photoperiod-induced increases in body weight and adiposity in female Syrian hamsters. PVN lesions did not affect body weight when hamsters were housed in a long photoperiod (LD, 16:8) and fed Purina laboratory rodent chow (No. 5001). However, when fed a high-fat diet both groups gained weight, and the hamsters with PVN lesions gained approximately twice as much as the sham-operated controls. When the hamsters were exposed to a short photoperiod (LD, 8:16), only the hamsters with sham lesions displayed the typical increase in body weight. No further increase in body weight or parametrial fat pad weight was seen when the hamsters with PVN lesions were exposed to the short photoperiod. The lack of a short photoperiod-induced increase in body weight gain in hamsters with PVN lesions seems unlikely to be due to a "ceiling effect" on body weight gain because we have routinely observed neurally intact, melatonin-treated female Syrian hamsters with body weight in excess of 250 g. Finally, the short photoperiod interrupted estrous cyclicity in sham-lesioned hamsters but not in those with PVN lesions. Thus, PVN lesions exaggerate dietary obesity but prevent short photoperiod-induced weight gains and vaginal acyclicity in female Syrian hamsters.

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Gonadal influences on adiposity.

Gonadal steroids affect energy balance and adiposity in a variety of mammalian species. For example, estradiol acts via multiple, redundant mechanisms to reduce body weight and adiposity. The steroid can act directly in the brain to decrease food intake and stimulate voluntary exercise. Sex hormones may act concurrently in non-neural peripheral tissues to alter metabolic processes and energy balance. White adipose tissue estrogen receptors may mediate estradiol-induced decreases in lipoprotein lipase activity and lipid storage. Finally, estradiol increases energy expenditure independent of any effects on voluntary exercise. Brown adipose tissue is a potential site for estradiol-induced thermogenesis.

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Ovarian modulation of lipoprotein lipase activity in white adipose tissue of ground squirrels.

Golden-mantled ground squirrels were ovariectomized (OVX) or Sham-OVX during the weight gain phase of the circannual body weight cycle. Other squirrels, OVX or Sham-OVX during the weight loss phase, were subcutaneously implanted with estradiol-filled or empty Silastic capsules. The mass of several fat pads as well as adipose tissue lipoprotein lipase (LPL) activity were determined at autopsy. Ovariectomy at either phase of the annual cycle was without effect on body weight. However, LPL activity of the parametrial fat pad was increased in OVX as compared to Sham-OVX squirrels. Fourteen days of estradiol treatment during the weight loss phase decreased the mass and LPL activity of the retroperitoneal fat depot but did not affect these parameters in perirenal adipose tissue. Although estradiol exerts different or opposite effects on body mass and food intake of rats and ground squirrels, ovariectomy and estrogen treatment affect LPL activity in a similar fashion in both species.

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Dietary obesity in exercising or cold-exposed Syrian hamsters.

High-fat diet-feeding increases body weight and adiposity in Syrian hamsters (Mesocricetus auratus), effects due in part to decreased energy expenditure. The effects of voluntary exercise- or cold exposure-induced increases in energy expenditure were examined in fat- or chow-fed, female Syrian hamsters. In Experiment 1, voluntary exercise (10 weeks) caused a moderate hyperphagia and actually increased body weight in both diet groups through increases in lean body mass. Carcass lipid was not affected by by exercise in chow-fed hamsters and only slightly reduced in fat-fed animals. In Experiment 2, chronic (8 weeks) cold exposure (5 degrees C) increased energy intake to the same extent in both dietary groups relative to the warm-exposed (23 degrees C) controls. High-fat diet-induced obesity was largely prevented by cold exposure. Cold exposure reduced lean body mass in chow-fed hamsters, but this carcass component was spared by fat-feeding. These results indicate that the increased metabolic demands of cold exposure were more effective in preventing this form of diet-induced obesity than those of voluntary exercise (80% and 17% reductions in carcass lipid, respectively). These results are discussed in terms of possible beneficial effects of eating a lipid-rich diet prior to winter.

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Adipose tissue lipoprotein lipase activity in rats maintained at a reduced body weight.

Male rats fed a cellulose-diluted diet maintained a reduced body weight. Adipose tissue lipoprotein lipase (LPL) activity decreased after two days of cellulose feeding, but was not different from chow-fed control levels with weight stabilized at 90% or 70% of the control group. Plasma triglyceride concentration decreased with weight loss and remained depressed with stabilized reduced weight. Regaining lost weight had no effect on LPL activity when compared with chow-fed controls or with levels obtained for the weight-reduced group. However, plasma triglyceride concentration returned to chow-fed control levels with weight gain. The disparity between these results and those obtained in obese human beings lends support to the hypothesis that the increase in adipose tissue LPL activity in weight-reduced obese human beings is indicative of a defect in regulation of adipose tissue metabolism.

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Effects of interscapular brown adipose tissue denervation on body weight and energy metabolism in ovariectomized and estradiol-treated rats.

Ovariectomy-induced increases and estradiol-induced decreased in body weight cannot be fully accounted for by changes in energy intake and appear to reflect alterations in thermogenesis. Because changes in energy expenditure have been linked to altered sympathetic nervous system (SNS) activity in brown adipose tissue (BAT), the role of estradiol in thermogenesis and body weight, as mediated by the SNS innervation of interscapular BAT (IBAT), was examined. The IBAT of ovariectomized rats was bilaterally or unilaterally surgically denervated. The chow-fed, bilaterally denervated group gained more weight than the unilaterally denervated or sham-operated group, an effect that was exaggerated by sucrose feeding. Food intake did not differ among the groups within each dietary condition. Estradiol benzoate (EB) injections decreased body weight in all groups. Bilateral, and to a lesser extent, unilateral IBAT denervation blocked the EB-induced increase in thermogenesis. Treatment with EB increased IBAT wet weight regardless of surgical treatment. Because IBAT denervation markedly decreased lipoprotein lipase activity and fatty acid synthesis/uptake, the estradiol-induced increase in denervated IBAT wet weight is most likely due to decreased lipolysis produced by the surgical sympathectomy. These results are discussed in terms of the role of the SNS and IBAT in the mediation of estradiol-induced changes in body weight and energy metabolism.

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Effects of photoperiod and gonadectomy on food intake, body weight, and body composition in Siberian hamsters.

Two experiments examined the effects of gonadectomy, photoperiod, and melatonin treatment on food intake, body weight, and carcass composition in male and female Siberian hamsters (Phodopus sungorus sungorus). Gonadectomy caused small decreases in body weight in both sexes but did not affect food intake. In males the weight reduction was due to small (nonsignificant) decreases in all carcass components. Ovariectomy caused a significant reduction in carcass lipid but did not affect lean body mass. A short photoperiod (8 h light, 16 h dark, LD 8:6) caused significant weight losses in all animals except ovariectomized females. Daily melatonin injections (12.5 micrograms sc, 3 h before lights-out) also reduced body weight in males and females housed in a long photoperiod (LD 16:8). The photoperiod- and melatonin-induced weight losses were almost entirely due to decreases in carcass lipid; lean body mass was unaffected by either treatment. Although short photoperiods and melatonin treatments decreased food intake, these changes were preceded by a significant loss of body weight. Thus photoperiod induced changes in food intake may be a consequence of the changes in body weight, rather than vice versa. These findings indicate that photoperiod and melatonin have important effects on adipose tissue mass in both Siberian and Syrian hamsters, even though one species gains weight (Syrian) and the other loses weight (Siberian) in short photoperiods.

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Short photoperiods counteract the effects of ovariectomy on energy balance of voles.

Adult female meadow voles maintained from birth in a long photoperiod (14 h light, 10 h darkness; LD 14:10) were ovariectomized or sham-ovariectomized and housed subsequently in long or short (LD 10:14) photoperiods for 10 wk. Absolute and relative daily food intake, body mass, carcass lipid and water content, and lipoprotein lipase activity of white adipose tissue were reduced in voles housed in short photoperiods. Ovariectomy resulted in increases in food intake and body weight and altered carcass composition in long-day voles, but these changes were negated in voles kept in short photoperiods. Responsiveness to short photoperiods promotes winter weight loss and subsequent energy intake savings and counteracts the body weight increases normally associated with gonadal quiescence and diminished hormone secretion.

Animals↗

Seasonal obesity in Syrian hamsters: effects of age, diet, photoperiod, and melatonin.

Two experiments examined the effects of photoperiod, melatonin, and diet on body weight in female Syrian hamsters (Mesocricetus auratus). In experiment 1, daily injections of 25 micrograms melatonin increased body weight when given 3 h before lights-out but not when given at the midpoint of the light phase, in a 16-h light-8-h dark cycle (LD 16:8). Ten micrograms of melatonin, given 3 h before lights-out, were sufficient to increase body weight and fat content, to increase interscapular brown adipose tissue weight, to decrease uterine weight, and to interrupt estrous cyclicity. However, 2.5 micrograms of melatonin increased body weight and fat content without affecting brown adipose tissue weight or reproductive function. In experiment 2, melatonin treatment, exposure to a short photoperiod (LD 8:16), and feeding a high-fat diet increased body weight gain in weanling (25-day-old) female hamsters. When melatonin treatment or high-fat diet were withdrawn, hamsters reduced their food intake, and their body weight and fat content returned to control levels. After 15-17 wk in the short photoperiod, hamsters also began to undereat, and their body weight and fat content returned to control levels. These findings suggest several conclusions. 1) As with the changes in reproductive function, melatonin is effective at increasing body weight only when given at certain times of day. 2) Not all end points are equally responsive to melatonin, suggesting that they are independent of one another. 3) Weanling hamsters respond to photoperiod, melatonin, and diet just as adults do. 4) The striking obesities induced by these manipulations are completely reversible.

Age Factors↗

Photoperiodic control of body weight and energy metabolism in Syrian hamsters (Mesocricetus auratus): role of pineal gland, melatonin, gonads, and diet.

The effects of photoperiod and the pineal hormone melatonin on the regulation of body weight and energy metabolism were examined in Syrian hamsters, Mesocricetus auratus. Short photoperiod-housed female and male hamsters showed increases in body weight gain, feed efficiency, carcass lipid, brown adipose tissue mass, and thermogenic capacity. These effects of short photoperiods were mimicked by afternoon melatonin injections to hamsters in long-day photoperiods and were exaggerated in hamsters fed high fat diets. To determine the role of the gonads in these effects, ovariectomized hamsters were treated similarly and found to exhibit changes in body weight and energy metabolism that were 80-90% of those in gonadally intact hamsters. The role of the pineal gland in short photoperiod-induced body weight gain was examined in sham-pinealectomized and pinealectomized hamsters. Short photoperiod-induced increases in body weight were seen in both pinealectomized and sham-pinealectomized hamsters. Thus, pinealectomy blocks the effects of short photoperiods on reproductive function and thyroid activity, but not on body weight regulation. These results suggest that the effects of short photoperiods on body weight and energy metabolism are mediated by multiple, redundant mechanisms involving decreases in gonadal hormone secretion, changes in melatonin secretion, and gonad- and pineal-independent changes. All of the effects of short photoperiods are exaggerated in hamsters fed a high fat diet. These changes may represent adaptive preparatory responses that enhance winter survival in Syrian hamsters.

Adipose Tissue, Brown↗

Hysterectomy facilitates proceptive behavior in rats.

The effects of hysterectomy on proceptive behavior were investigated using several doses of estradiol benzoate (EB) and progesterone (P) in female rats. One week after surgery, ovariectomized (OV) and ovariectomized-hysterectomized (OH) rats were given three daily injections of 1.0 or 2.0 micrograms EB followed by 0.5 mg P or oil on the fourth day and were tested for solicitation 4 hr later. The same animals received 1.0 or 2.0 micrograms EB plus 0.1 mg P, or 4.0 micrograms EB plus oil on the same schedule a week following the first test and were tested again. Ovariectomized-hysterectomized animals receiving 0.5 mg P, regardless of the EB dose, showed significantly higher solicitation scores than OV animals, but the scores of the EB-primed OV and OH rats receiving 0.1 mg P or oil vehicle did not differ.

Animals↗

Effect of sucrose overfeeding on brown adipose tissue lipogenesis and lipoprotein lipase activity in rats.

During cold-induced nonshivering thermogenesis, interscapular brown adipose tissue (BAT) lipoprotein lipase (LPL) activity and lipogenesis are elevated. Because of the many similarities between cold- and diet-induced thermogenesis, we examined the effect of ad libitum access to a 32% sucrose solution on caloric intake, adiposity, and BAT enzyme activities in male rats. Daily caloric intakes of sucrose-fed animals were elevated by 20%-25%, and 8 wk of sucrose feeding doubled carcass fat content. This sucrose-feeding induced obesity was associated with increases in circulating triglyceride and insulin levels as well as increased retroperitoneal white adipose tissue LPL activity. However, the increased carcass lipid content accounted for less than half of the excess calories ingested by the sucrose-fed rats. Sucrose feeding stimulated in vivo lipogenesis in BAT and elevated BAT fatty acid synthetase and acetyl-CoA carboxylase activities but not LPL activity. These findings suggest that overeating enhances endogenous lipogenesis but not uptake of circulating triglyceride in BAT. Thus, both cold- and diet-induced thermogenesis increase BAT lipogenesis, while only cold-induced thermogenesis is associated with elevated LPL activity in BAT.

Adipose Tissue↗