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Query: UMLS:C0020505 (hyperphagia)
 6,116 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Insulin-induced anestrus in Syrian hamsters. 199 15

The high prevalence of obesity and its well documented association with the cardiovascular risk factors diabetes mellitus, dyslipidemia and hypertension represents a major problem for the general health status of industrialized societies. Although numerous studies have shown that genetic factors have a major influence on the regulation of energy homeostasis and the susceptibility to obesity, the genes and predisposing mutations involved are insufficiently understood. Among several known rodent models of obesity due to single gene mutations, mice homozygous for the obese (ob) gene exhibit massive early-onset obesity, hyperphagia, non-insulin-dependent diabetes mellitus, defective thermoregulation and infertility. Recently the ob gene was identified by positional cloning and shown to be mutated in ob/ob mice. Leptin, the product of the ob gene, is a 167-amino acid secreted protein that is synthesized exclusively in adipose tissue. With the exception of ob/ob mice, circulating plasma leptin is elevated in obesity. Administration of recombinant leptin to ob/ob mice reduces fat mass, food intake, hyperglycemia and hyperinsulinemia. The various effects of the hormone are mediated by leptin receptors expressed at high levels in the hypothalamus, but also in several other non-neuronal tissues. A mutation in the leptin receptor gene is responsible for the obese phenotype of db/db mice. Plasma leptin in humans is positively correlated with body fat mass, suggesting that leptin resistance rather than leptin deficiency is a common feature of human obesity. This review briefly summarizes the current status of the rapidly growing evidence that leptin plays an important role in the regulation of body weight and fat deposition.
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PMID:Regulation of energy balance by leptin. 888 45

The adipocyte-specific hormone leptin, the product of the obese (ob) gene, regulates adipose-tissue mass through hypothalamic effects on satiety and energy expenditure. Leptin acts through the leptin receptor, a single-transmembrane-domain receptor of the cytokine-receptor family. In rodents, homozygous mutations in genes encoding leptin or the leptin receptor cause early-onset morbid obesity, hyperphagia and reduced energy expenditure. These rodents also show hypercortisolaemia, alterations in glucose homeostasis, dyslipidaemia, and infertility due to hypogonadotropic hypogonadisms. In humans, leptin deficiency due to a mutation in the leptin gene is associated with early-onset obesity. Here we describe a homozygous mutation in the human leptin receptor gene that results in a truncated leptin receptor lacking both the transmembrane and the intracellular domains. In addition to their early-onset morbid obesity, patients homozygous for this mutation have no pubertal development and their secretion of growth hormone and thyrotropin is reduced. These results indicate that leptin is an important physiological regulator of several endocrine functions in humans.
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PMID:A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction. 953 16

Excessive diversion of metabolic fuels away from oxidation and into adipose tissue storage depots, such as underfeeding or extraordinary levels of energy expenditure, can induce nutritional infertility. Treatment with pharmacological doses of insulin reduces metabolic fuel availability and suppresses both ovulatory cyclicity and pulsatile luteinizing hormone release in females of several mammalian species, but little attention has been paid to the effects of insulin treatments on reproductive behaviors. Ovariectomized Syrian hamsters were injected with long-acting insulin every 12 h for 72 h and were prevented from overeating by limiting their intake to approximately 110% of pretreatment levels. When given estradiol and progesterone, insulin-treated hamsters exhibited significantly reduced levels of sexual receptivity compared with saline-treated controls. This insulin-induced inhibition of estrous behavior was prevented by lesions of the area postrema. Insulin treatments also caused changes in the number of detectable estrogen receptor immunoreactive cells in the hypothalamus and preoptic area. Therefore, insulin-induced repartitioning of metabolic fuels induces changes in estrous behavior and neural estrogen receptors that are indistinguishable from those caused by food deprivation, cold exposure, or treatment with metabolic inhibitors.
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PMID:Insulin-induced repartitioning of metabolic fuels inhibits hamster estrous behavior: role of area postrema. 957 74

Several observations suggest the presence of an interaction between immune and the endocrine systems. Leptin is an adipocyte-derived hormone, that belongs structurally to the long-chain helical cytokine family such as interleukin-2 (IL-2), interleukin-12 (IL-12), growth hormone (GH), and signals by a class I cytokine receptor (Ob-R). This cytokine represents an important link between fat mass on the one side and the regulation of energy balance and reproductive function on the other. Indeed, obese leptin-deficient ob/ob mice display low body temperature, hyperphagia, infertility and evidence of immune defects with lymphoid organ atrophy, mainly affecting thymic size and cellularity. Acute starvation, associated with decreased leptin levels, causes thymic atrophy and reduces the delayed type hypersensitivity (DTH) reaction to antigens in normal mice, resembling that observed in ob/ob mice. Leptin replacement reverses the immunosuppressive effects of acute starvation in mice. Leptin differentially affects the in vitro proliferation and cytokine production by naive and memory T cells, increasing IL-2 secretion and proliferation of naive T cells, while inducing IFN-g production in memory T cells with little effect on their proliferation. Presence of leptin seems to be necessary for the induction and maintenance of the pro-inflammatory Th1 immune response. These findings support the hypothesis that leptin plays a key role in linking nutritional state to the T cell function. According to this view, leptin might represent an important target for immune intervention in a variety of pathophysiological conditions.
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PMID:Leptin and the immune system: how nutritional status influences the immune response. 1070 94

In these studies we investigated the time course of changes in circulating leptin levels in lactating rats and the dependence of these changes on the energetic cost of lactation and evaluated the contribution of changes in leptin levels to lactational hyperphagia and infertility. In the first experiment, plasma leptin levels were measured on Days 5, 10, 15, 20, and 25 postpartum in freefeeding lactating rats and age-matched virgin females. Retroperitoneal and parametrial fat pads weights were obtained from the same females. In the second experiment the same measures, together with plasma insulin and prolactin levels, were taken on Days 15 and 20 postpartum from galactophore-cut and sham-operated females. In Experiments 3 and 4, the effects of exogenous leptin administration, either subcutaneously (sc) or intracerebroventricularly (icv), on lactational anovulation, maternal food intake, and dam and litter weights were examined. Circulating leptin levels decreased in lactating rats. Leptin levels were highly positively correlated with fat pad weight. Eliminating the energetic costs of lactation by preventing milk delivery induced dramatic increases in plasma leptin and insulin levels and also increased adiposity. Exogenous leptin administration did not affect length of lactational anovulation but reduced food intake, maternal body weight, and litter weight gain when given centrally and maternal body weight when given systemically. Together, these data show that the energetic costs of lactation are associated with a fall in circulating leptin levels but that these do not make a major contribution to the suppression of reproduction in lactating rats; however, they may be permissive to the hyperphagia of lactation.
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PMID:Changes in leptin levels during lactation: implications for lactational hyperphagia and anovulation. 1086 Jun 79

Leptin, the product of the obese gene, is a circulating hormone secreted primarily from adipocytes. The lack of leptin in ob/ob mice, who are homozygous for the obese gene, results in hyperglycemia, hyperinsulinemia, hyperphagia, obesity, infertility, decreased brain size and decreased stature. To this end, we investigated the role of leptin as a hormonal regulator of bone growth. Leptin administration led to a significant increase in femoral length, total body bone area, bone mineral content and bone density in ob/ob mice as compared to vehicle treated controls. The increase in total body bone mass was a result of an increase in both trabecular and cortical bone mass. These results suggest that the decreased stature of the ob/ob mouse is due to a developmental defect that is readily reversible upon leptin administration. Our demonstration that the signalling or long form (Ob-Rb) of the leptin receptor is present in both primary adult osteoblasts and chondrocytes suggests that the growth promoting effects of leptin could be direct. In summary, these results indicate a novel role for leptin in skeletal bone growth and development.
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PMID:Leptin is a potent stimulator of bone growth in ob/ob mice. 1102 68

Successful reproduction requires the accumulation of energy reserves. Although acute and chronic food deprivation disrupts reproduction, surprisingly, an over-abundance of energy reserves can also result in infertility. The infertility of obese, ob/ob mice can be reversed by the reintroduction of leptin, the protein product of the ob gene. In rats, energy reserves are increased during pregnancy by far accumulation and during lactation by hyperphagia. We have therefore investigated the interactions of leptin and food intake during late pregnancy and lactation in rats. Cycling rats consume their daily food intake during the dark phase and this is accompanied by a subsequent increase in plasma leptin concentration compared to light levels. During late pregnancy, rats increase their food intake during the dark phase and this is accompanied by a nocturnal increase in plasma leptin level. However, the nocturnal increase is not seen on the day prior to parturition, and is absent throughout lactation. Surprisingly, despite the massive increase in food intake during lactation plasma leptin levels continue to fall, suggesting that leptin release in response to food intake is suppressed during lactation. Furthermore, central leptin administration is less effective in reducing food intake in late pregnant and early lactating rats compared to cycling rats which suggests that these rats are insensitive to leptin. This may result from downregulation of brain leptin receptors. Decreased leptin production and action during late pregnancy and lactation will result in a decreased satiety effect, with up-regulation of orexigenic factors that produce hyperphagia, so allowing adequate energy intake for successful rearing of offspring.
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PMID:Food intake and leptin during pregnancy and lactation. 1158 32

Signal transducer and activator of transcription (STAT)3 is widely expressed in the CNS during development and adulthood. STAT3 has been implicated in the control of neuron/glial differentiation and leptin-mediated energy homeostasis, but the physiological role and degree of involvement of STAT3 in these processes is not defined and controversial because of the lack of a direct genetic model. To address this, we created mice with a neural-specific disruption of STAT3 (STAT3(N-/-)). Surprisingly, homozygous mutants were born at the expected Mendelian ratio without apparent developmental abnormalities but susceptible to neonatal lethality. Mutants that survived the neonatal period were hyperphagic, obese, diabetic, and infertile. Administering a melanocortin-3/4 receptor agonist abrogated the hyperphagia and hypothalamic immunohistochemistry showed a marked reduction in proopiomelanocortin with an increase in neuropeptide Y and agouti-related protein. Mutants had reduced energy expenditure and became hypothermic after fasting or cold stress. STAT3(N-/-) mice are hyperleptinemic, suggesting a leptin-resistant condition. Concomitant with neuroendocrine defects such as decreased linear growth and infertility with accompanying increased corticosterone levels, this CNS knockout recapitulates the unique phenotype of db/db and ob/ob obese models and distinguishes them from other genetic models of obesity. Thus, STAT3 in the CNS plays essential roles in the regulation of energy homeostasis and reproduction.
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PMID:Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. 1507 Jul 74

Mitochondria play critical roles in oxidative phosphorylation and energy metabolism. Increasing evidence supports that mitochondrial DNA (mtDNA) damage and dysfunction play vital roles in the development of many mitochondria-related diseases, such as obesity, diabetes mellitus, infertility, neurodegenerative disorders, and malignant tumors in humans. Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) transgenic (TG) mice were produced by nuclear microinjection. Transgene integration was analyzed by PCR. Transgene expression was measured by RT-PCR and Western blot analysis. Mitochondrial DNA damage was analyzed by mutational analyses and measurement of mtDNA copy number. Total fat content was measured by a whole-body scan using dual-energy X-ray absorptiometry. The hOGG1 overexpression in mitochondria increased the abundance of intracellular free radicals and major deletions in mtDNA. Obesity in hOGG1 TG mice resulted from increased fat content in tissues, produced by hyperphagia. The molecular mechanisms of obesity involved overexpression of genes in the central orexigenic (appetite-stimulating) pathway, peripheral lipogenesis, down-regulation of genes in the central anorexigenic (appetite-suppressing) pathway, peripheral adaptive thermogenesis, and fatty acid oxidation. Diffuse hepatosteatosis, female infertility, and increased frequency of malignant lymphoma were also seen in these hOGG1 TG mice. High levels of hOGG1 expression in mitochondria, resulting in enhanced oxidative DNA damage processing, may be an important factor in human metabolic syndrome, infertility, and malignancy.
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PMID:Obesity and hepatosteatosis in mice with enhanced oxidative DNA damage processing in mitochondria. 2143 53


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