Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin

Yura, Shigeo; Ogawa, Yoshihiro; Sagawa, Norimasa; Masuzaki, Hiroaki; Itoh, Hiroaki; Ebihara, Ken; Aizawa-Abe, Megumi; Fujii, Shingo; Nakao, Kazuwa

doi:10.1172/jci8353

Cited by 138 publications

(97 citation statements)

References 56 publications

(59 reference statements)

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“…Jejum acompanhado da queda da leptina está associado à redução da atividade secretória do LH em várias espécies (7). Mais recentemente, um estudo demonstrou que a cepa transgênica de camundongos que expressa leptina exageradamente tem a sua puberdade acelerada (65). Os autores notaram porém o aparecimento de hipogonadismo hipogonadotrófico de início tardio nestes mesmos animais.…”

Section: Reproduçãounclassified

Leptina: o diálogo entre adipócitos e neurônios

Negrão¹,

Licinio

2000

Arq Bras Endocrinol Metab

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The discovery of leptin led to a renewed interest in the study of enegy homeostasis. It is now recognized that white adipose tissue is the major site of leptin synthesis. After it is secreted into the bloodstream leptin binds itself to specific receptors in the brain, providing the central nervous system with a satiety signal that reflects the amount of energy stored as fat. Acting through receptors that transduce a signal by the JAK/STAT pathway, leptin modifies the expression and activity of hypothalamic peptides that regulate appetite and energy expenditure. In addition, leptin signals nutritional status to other physiological systems and modulates the function of several target glands. More recently, recombinant leptin was successfully given to an obese patient with leptin deficiency due to a mutation in the ob gene. On the other hand, the effects of recombinant leptin in the only study with obese patients and increased levels of circulating leptin were less impressive.Here we review the complexity of leptin actions with a focus on its integrative role as a signal of nutritional status for the organism.

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Section: Reproduçãounclassified

Leptina: o diálogo entre adipócitos e neurônios

Negrão¹,

Licinio

2000

Arq Bras Endocrinol Metab

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“…We previously created transgenic skinny mice overexpressing leptin under the control of the liver-specific human serum amyloid P component promoter [8]. The "hyperleptinaemia" of these skinny mice causes the disappearance of lipids from the adipose tissue and provides a unique experimental system to investigate the long-term in vivo effects of chronic hyperleptinaemia [8,9,10]. The skinny mice have increased glucose metabolism and insulin sensitivity, accompanied by the activation of insulin signalling for glucose disposal in the skeletal muscle and liver [8].…”

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confidence: 99%

Leptin as an adjunct of insulin therapy in insulin-deficient diabetes

et al. 2003

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Aims/hypothesis. The purpose of this study was to assess the therapeutic implication of leptin in insulindeficient diabetes. Methods. Insulin-deficient diabetes was induced by streptozotocin (STZ) in transgenic skinny mice overexpressing leptin. Plasma concentrations of glucose, insulin, and leptin were measured. The effects on body weight, food intake, and hypothalamic gene expressions were analyzed. After diabetes was induced, graded doses of insulin ranging from 0.4 to 51.2 mU·g -1 ·day -1 were injected. Co-administration of leptin and insulin was also carried out using osmotic pumps. Results. After STZ injection, both transgenic and nontransgenic littermates developed marked hyperglycaemia as a result of severe hypoinsulinaemia [termed diabetic transgenic skinny mice overexpressing leptin (diabetic TGM) and diabetic non-transgenic littermates (diabetic WT) respectively], although diabetic TGM were more sensitive to exogenously administered insulin than diabetic WT. Diabetic WT were hypoleptinaemic and hyperphagic relative to non-diabetic WT, whereas diabetic TGM, which remained hyperleptinaemic, were less hyperphagic than diabetic WT. After STZ injection, hypothalamic expressions of orexigenic and anorexigenic peptide mRNAs were upregulated and down-regulated, respectively, in diabetic WT, whereas they were unchanged in diabetic TGM. Diabetic TGM became normoglycaemic, when treated with insulin at such doses that did not improve hyperglycaemia in diabetic WT. We found that a subthreshold dose of insulin that does not affect glucose homeostasis is effective in improving the diabetes in normal mice rendered diabetic by STZ injection, when combined with leptin. Conclusions/interpretation. This study suggests that leptin could be used as an adjunct of insulin therapy in insulin-deficient diabetes, thereby providing an insight into the therapeutic implication of leptin as an anti-diabetic agent. [Diabetologia (2003[Diabetologia ( ) 46:1329[Diabetologia ( -1337

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“…Like human, dietary-induced obesity is a polygenic trait which combines the contribution of genetic influence to the environmental one; thus, resistance to the endocrine effects of circulating leptin and insulin is strongly related to adherent increases in their circulating concentration levels following increased dietary-intake [19]. Furthermore, concurrent to the emergence of the phenotype of hyperleptinemic obese mutant mice, was the fact that chronically elevated levels of leptin may also be associated with hypothalamic infertility, suggesting that leptin resistance impairs GnRH pulsatile secretion and energy balance closing the vicious cycle of obesity [20].…”

Section: Models Of Obesity and Subfertility; The Bridging Role Of Leptinmentioning

confidence: 99%

Obesity and Female Fertility: The Bridging Role of Leptin

Karoutsos¹

2017

J Data Mining Genomics Proteomics

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Leptin secretion is a requirement in order for both of energy balance and reproductive capacity to be preserved. That is because leptin plays an important role in appetite regulation and balance of body weight. Leptin binds to leptin receptor in the cells of the hypothalamus. This stimulates an intracrine signaling pathway that drives downregulation of the receptors expression involved in appetite increase. It is clearly set that leptin impairs production of sex steroid hormones in granulosa cells. In addition, alterations noted in follicular fluid from obese women include increased androgen activity and decreased human chorionic gonadotropin levels by other studies. Likewise, adiponectin levels are inversely correlated with levels of insulin, which by inhibiting the production of hepatic sex hormone binding globulin, because increased levels of androgens. On meeting with the fertility problems that arise among these women, scientists must understand the pathophysiology of adipose signaling on reproductive function.

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Accelerated puberty and late-onset hypothalamic hypogonadism in female transgenic skinny mice overexpressing leptin

Cited by 138 publications

References 56 publications

Leptina: o diálogo entre adipócitos e neurônios

Leptina: o diálogo entre adipócitos e neurônios

Leptin as an adjunct of insulin therapy in insulin-deficient diabetes

Obesity and Female Fertility: The Bridging Role of Leptin

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