Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress

González-García, Ismael; Contreras, Cristina; Estévez-Salguero, Ánxela; Ruíz-Pino, Francisco; Colsh, Benoit; Pensado, Iván; Liñares-Pose, Laura; Rial-Pensado, Eva; Morentin, Pablo Blanco Martínez de; Fernø, Johan; Diéguez, Carlos; Nogueiras, Rubén; Stunff, Hervé Le; Magnan, Christophe; Tena‐Sempere, Manuel; López, Miguel

doi:10.1016/j.celrep.2018.09.038

Cited by 72 publications

(77 citation statements)

References 67 publications

(229 reference statements)

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“…Conversely, VMH stimulation increases BAT thermogenesis . Recent evidence suggests that hormones such as oestrogen and 3,3′,5‐triiodothyronine (T3) act in the VMH to stimulate the sympathetic activation of BAT thermogenesis . Interestingly, T3 action in the VMH is also required for the ability of this hormone to promote WAT browning and protect against obesity .…”

Section: Vmhmentioning

confidence: 99%

“…These effects of VMH ERα recapitulate the effects of peripheral and central administration of 17β‐oestradiol (E 2 ). Moreover, central E 2 decreases hypothalamic endoplasmic reticulum stress, suggesting a potential mechanism for the metabolic effects of this hormone …”

Section: Vmhmentioning

confidence: 99%

“…Glucose sensing and oestrogen regulation of VMH GI neurones are both dependent on the cellular fuel sensor, AMP‐activated protein kinase (AMPK) . Oestrogens also regulate energy homeostasis via AMPK‐dependent VMH projections to the lateral/perifornical hypothalamus (LH/PFH) orexin neurones . In this review, we consider the mechanisms by which VMH oestrogen may regulate glucose and energy homeostasis.…”

Section: Introductionmentioning

confidence: 99%

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Ventromedial hypothalamus glucose‐inhibited neurones: A role in glucose and energy homeostasis?

Hirschberg

Sarkar

Teegala

et al. 2019

J Neuroendocrinology

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The ventromedial hypothalamus (VMH) plays a complex role in glucose and energy homeostasis. The VMH is necessary for the counter‐regulatory response to hypoglycaemia (CRR) that increases hepatic gluconeogenesis to restore euglycaemia. On the other hand, the VMH also restrains hepatic glucose production during euglycaemia and stimulates peripheral glucose uptake. The VMH is also important for the ability of oestrogen to increase energy expenditure. This latter function is mediated by VMH modulation of the lateral/perifornical hypothalamic area (lateral/perifornical hypothalamus) orexin neurones. Activation of VMH AMP‐activated protein kinase (AMPK) is necessary for the CRR. By contrast, VMH AMPK inhibition favours decreased basal glucose levels and is required for oestrogen to increase energy expenditure. Specialised VMH glucose‐sensing neurones confer the ability to sense and respond to changes in blood glucose levels. Glucose‐excited (GE) neurones increase and glucose‐inhibited (GI) neurones decrease their activity as glucose levels rise. VMH GI neurones, in particular, appear to be important in the CRR, although a role for GE neurones cannot be discounted. AMPK mediates glucose sensing in VMH GI neurones suggesting that, although activation of these neurones is important for the CRR, it is necessary to silence them to lower basal glucose levels and enable oestrogen to increase energy expenditure. In support of this, we found that oestrogen reduces activation of VMH GI neurones in low glucose by inhibiting AMPK. In this review, we present the evidence underlying the role of the VMH in glucose and energy homeostasis. We then discuss the role of VMH glucose‐sensing neurones in mediating these effects, with a strong emphasis on oestrogenic regulation of glucose sensing and how this may affect glucose and energy homeostasis.

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Section: Vmhmentioning

confidence: 99%

Section: Vmhmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ventromedial hypothalamus glucose‐inhibited neurones: A role in glucose and energy homeostasis?

Hirschberg

Sarkar

Teegala

et al. 2019

J Neuroendocrinology

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“…Lin et al have recently demonstrated that the estradiol/ERα signaling axis upregulates the mitochondrial bioenergetic system to improve osteoblast maturation . It has recently been shown that estradiol down‐regulates hypothalamic ceramide‐induced lipotoxicity and ER stress and up‐regulates energy balance in ovariectomized rats . 17β‐Estradiol supplementation has been demonstrated to increase CHOP expression in estrogen apoptosis‐sensitive colon cancer cells .…”

Section: Resultsmentioning

confidence: 99%

Gender difference of CCAAT/enhancer binding protein homologous protein deficiency in susceptibility to osteopenia

Lin

et al. 2019

Journal Orthopaedic Research

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Expression of CCAAT/enhancer binding protein (C/EBP) homologous protein (CHOP) is induced during endoplasmic reticulum (ER) stress, which is related to apoptosis in several cell types. CHOP null mice have been exhibited to decrease bone formation. However, a study of transgenic mice overexpressing CHOP in the bone microenvironment showed that CHOP overexpression impairs the osteoblastic function leading to osteopenia. The regulatory role of CHOP in bone formation is controversial and still remains to be clarified. Here, we investigated the alterations in bone microstructure of CHOP knockout (Chop−/−) mice and tested the gender difference of CHOP deficiency in susceptibility to osteopenia. Adult female and male mice (WT) and Chop−/− mice were used. The microcomputed tomography (µCT) analysis in trabecular bone and cortical bone of tibia was determined. Trabecular bone volume fraction (BV/TV), trabecular number, and bone mineral density (BMD) in tibia are markedly decreased in both male and female Chop−/− mice compared to the control WT mice. Unexpectedly, the BMD and BV/TV in trabecular bone of tibia in female Chop−/− mice were significantly lower than in male Chop−/− mice. The similar results could also be observed in the cortical bone of tibia in Chop−/− mice. This gender difference was also observed in the decreased capacity of osteoblast differentiation of bone marrow cells isolated from Chop−/− mice. These results indicated that ER stress‐related CHOP signaling might play an important role in the bone formation in a mouse model, especially in females. There is the gender difference of CHOP deficiency in susceptibility to osteopenia. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res

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“…through ceramide-mediated lipotoxicity and alleviated through the chaperone GRP78/BiP (glucose-regulated protein 78 kDa/binding immunoglobulin protein) (Contreras et al 2014(Contreras et al , 2017a. The mechanisms by which estradiol and thyroid hormones positively regulate energy balance also include the suppression of VMH endoplasmic reticulum (Martinez-Sanchez et al 2017b, Gonzalez-Garcia et al 2018.…”

Section: Neuronal Control Of Wat Beigingmentioning

confidence: 99%

Adipose tissue browning in mice and humans

Herz

Kiefer

2019

Journal of Endocrinology

113

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In the midst of an obesity epidemic, the promotion of brown adipose tissue (BAT) function and the browning of white adipose tissue (WAT) have emerged as promising therapeutic targets to increase energy expenditure and counteract weight gain. Despite the fact that the thermogenic potential of bone fide BAT in rodents is several orders of magnitudes higher than white fat containing brite/beige adipocytes, WAT browning represents a particularly intriguing concept in humans given the extreme amount of excess WAT in obese individuals. In addition, the clear distinction between classic brown and beige fat that has been proposed in mice does not exist in humans. In fact, studies of human BAT biopsies found controversial results suggesting both classic brown and beige characteristics. Irrespective of the true ‘color’, accumulating evidence suggests the induction of thermogenic adipocytes in human WAT depots in response to specific stimuli, highlighting that WAT browning may occur in both, mice and humans. These observations also emphasize the great plasticity of human fat depots and raise important questions about the metabolic properties of thermogenically active adipose tissue in humans and the potential therapeutic implications. We will first review the cellular and molecular aspects of selected adipose tissue browning concepts that have been identified in mouse models with emphasis on neuronal factors, the microbiome, immune cells and several hormones. We will also summarize the evidence for adipose tissue browning in humans including some experimental pharmacologic approaches.

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Estradiol Regulates Energy Balance by Ameliorating Hypothalamic Ceramide-Induced ER Stress

Cited by 72 publications

References 67 publications

Ventromedial hypothalamus glucose‐inhibited neurones: A role in glucose and energy homeostasis?

Ventromedial hypothalamus glucose‐inhibited neurones: A role in glucose and energy homeostasis?

Gender difference of CCAAT/enhancer binding protein homologous protein deficiency in susceptibility to osteopenia

Adipose tissue browning in mice and humans

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