Minireview: Metabolic control of the reproductive physiology: Insights from genetic mouse models

Bellefontaine, Nicole; Elias, Carol F.

doi:10.1016/j.yhbeh.2014.04.007

Cited by 16 publications

(3 citation statements)

References 104 publications

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“…Estrogens (17β-estradiol) have been demonstrated to play a role in regulating adiposity, reproduction [1] and insulin sensitivity [2,3]. Additionally, recent papers have demonstrated a critical role for three putative estrogen receptors in modulating adiposity, insulin sensitivity, and energy homeostasis.…”

Section: Introductionmentioning

confidence: 99%

Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis

Davis

Carstens

Irani

et al. 2014

Hormones and Behavior

110

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The classical estrogen receptors, estrogen receptor-α and estrogen receptor-β are well established in the regulation of body weight and energy homeostasis in both male and female mice, whereas, the role for G protein-coupled estrogen receptor 1 (GPER) as a modulator of energy homeostasis remains controversial. This study sought to determine whether gene deletion of GPER (GPER KO) alters body weight, body adiposity, food intake, and energy homeostasis in both males and females. Male mice lacking GPER developed moderate obesity and larger adipocyte size beginning at 8 weeks of age, with significant reductions in energy expenditure, but not food intake or adipocyte number. Female GPER KO mice developed increased body weight relative to WT females a full 6 weeks later than the male GPER KO mice. Female GPER KO mice also had reductions in energy expenditure, but not significant increases in body fat content. Consistent with their decrease in energy expenditure, GPER KO males and females showed significant reductions in two brown fat thermogenic proteins. GPER KO females, prior to their divergence in body weight, were less sensitive than WT females to the feeding-inhibitory effects of leptin and CCK. Additionally, body weight was not as modulated by ovariectomy or estradiol replacement in GPER KO mice. Estradiol treatment activated phosphorylated extracellular signal-regulated kinase (pERK) in WT but not GPER KO females. For the first time, GPER expression was found in the adipocyte but not the stromal fraction of adipose tissue. Together, these results provide new information elucidating a sexual dimorphism in GPER function in the development of postpubertal energy balance.

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Section: Introductionmentioning

confidence: 99%

Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis

Davis

Carstens

Irani

et al. 2014

Hormones and Behavior

110

View full text Add to dashboard Cite

show abstract

“…Recently, many efforts have been made to understand how peripheral metabolic hormones mediate aspects of the neuroendocrine reproductive axis, with a particular interest to leptin. 1,2 Leptin is a 16-kDa protein transcribed from the ob gene and secreted by the adipocytes, 3,4 mainly in white adipose tissue, 5 serving as a link between fat and brain. Long-term intake of high-fat diet induces increase in plasma leptin.…”

Section: Introductionmentioning

confidence: 99%

Decreased Implantation Number After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure

et al. 2017

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Leptin is a protein secreted by the adipocytes, which serves as a link between fat and brain. Its main action is to decrease appetite and increase energy expenditure, but it is also involved in the control of different neuroendocrine systems, including gonadal axis. Although the effects of leptin deficiency on reproduction are well recognized, the effect of excess leptin on male reproductive function is not clear. The aim of this study was to evaluate fertility and sperm parameters of male rats exposed to exogenous leptin. A group of adult male rats received exogenous leptin intraperitoneally (30 μg/kg/day) for 42 days, and a control group received only the vehicle during the same period. After the treatment, animals were evaluated for sperm count, sperm motility, and fertility after intrauterine artificial insemination. There was no statistically significant difference between the groups related to sperm production, sperm concentration, and sperm motility. However, fertility evaluation after artificial insemination showed a quantitative decrease in the uterus plus fetuses weight, number of implantation sites, and number of live fetuses. The fertility potential showed a reduction of about 40%, whereas the preimplantation loss rate increased more than 2-fold in leptin-treated animals. In conclusion, leptin administration to nonobese male rats impairs ability of treated animals to generate offspring, since the occurrence of implantation was diminished. So leptin can impair sperm quality, affecting the reproductive capacity.

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“…It is largely assumed that neuronal insulin signalling mediates the central effects of insulin on fertility, as demonstrated by the fact that the ‘brain‐specific’ InsR KO mice are often incorrectly referred to as neurone‐specific InsR KO mice . These mice were generated using Nestin ‐Cre mediated recombination and, because Nestin is highly expressed in neural progenitor cells (from which glial cells are also derived), Cre‐mediated recombination of the Insr gene in the brain‐specific InsR KO mice would have occurred in both the central nervous system (CNS) and peripheral nervous system and would not have been restricted to neurones .…”

mentioning

confidence: 99%

Insulin Does Not Target CamkIIα Neurones to Critically Regulate the Neuroendocrine Reproductive Axis in Mice

Evans

Rizwan

Anderson

2015

J Neuroendocrinology

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Insulin signalling in the brain plays an important role in the central regulation of energy homeostasis and fertility, such that mice exhibiting widespread deletion of insulin receptors (InsR) throughout the brain and peripheral nervous system display diet sensitive obesity and hypothalamic hypogonadism. However, the specific cell types mediating the central effects of insulin on fertility remain largely unidentified. To date, the targeted deletion of InsR from individual neuronal populations implicated in the metabolic control of fertility has failed to recapitulate the hypogonadic and subfertile phenotype observed in brain-specific InsR knockout mice. Because insulin and leptin share similar roles as centrally-acting metabolic regulators of fertility, we used the Cre-loxP system to generate mice with a selective inactivation of the Insr gene from the same widespread neuronal population previously shown to mediate the central effects of leptin on fertility by crossing Insr-flox mice with calcium/calmodulin-dependent protein kinase type IIα (CamkIIα)-Cre mice. Multiple reproductive and metabolic parameters were then compared between male and female Insr-flox/Cre-positive (CamK-IRKO) and Insr-flox/Cre-negative control mice. Consistent with brain-specific InsR knockout mice, CamK-IRKO mice exhibited a mild but significant obesogenic phenotype. Unexpectedly, CamK-IRKO mice exhibited normal reproductive maturation and function compared to controls. No differences in the age of puberty onset, oestrous cyclicity or fecundity were observed between CamK-IRKO and control mice. We conclude that the central effects of insulin on the neuroendocrine reproductive axis are not critically mediated via the same neuronal populations targeted by leptin.

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Minireview: Metabolic control of the reproductive physiology: Insights from genetic mouse models

Cited by 16 publications

References 104 publications

Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis

Sexually dimorphic role of G protein-coupled estrogen receptor (GPER) in modulating energy homeostasis

Decreased Implantation Number After In Utero Artificial Insemination Can Reflect an Impairment of Fertility in Adult Male Rats After Exogenous Leptin Exposure

Insulin Does Not Target CamkIIα Neurones to Critically Regulate the Neuroendocrine Reproductive Axis in Mice

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