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Duquenne et al. show that tanycyte leptin receptor expression is required for leptin to enter the brain and regulate peripheral lipogenesis and pancreatic β-cell function.

The median eminence (ME) at the base of the brain controls body homeostasis. Here, the authors describe a functional tanycyte subpopulation at the ME which tastes the surrounding milieu, responds to metabolic signals and regulates glucose homeostasis.

The hypothalamus is the main integrator of endocrine regulation. Glia–neuron interactions contribute to physiological processes such as puberty, the maintenance of bodily homeostasis and ageing. Here, Vincent Prevot and Jerome Clasadonte discuss glia–neuron interactions in the control of hypothalamic neuroendocrine function.

GnRH neurons control their own connectivity and function as well as the sexual maturation of the individual by using prostaglandin D₂ DP1 signaling to recruit and stably associate with newborn astrocytes in the preoptic region during infancy in rodents.

Vincent Prevot and colleagues discuss the role of neuronal nitric oxide (NO) in the regulation of key physiological processes controlled by the preoptic region of the hypothalamus, including reproduction. How deregulation of NO production might be involved in the pathophysiology of brain diseases, for which hormonal imbalances during postnatal development could be a risk factor, is also discussed.

Reproduction in mammals is dependent on the function of specific neurons that secrete gonadotropin-releasing hormone (GnRH) and project their axons to the median eminence (ME) of the hypothalamus. Here the authors show that Semaphorin7A signaling plays a role in mediating the plasticity of GnRH axon terminals and tanycytes in the ME.

The authors show that a gene expression switch operated by microRNAs regulates the control of puberty onset and adult fertility by the CNS by triggering increased hypothalamic Gnrh mRNA expression during the infantile period of postnatal development.

Energy homeostasis requires brain sensing of peripheral metabolic signals. Here, the authors show that energy-state-dependent aggrecan deposits by hypothalamic neurons at a key interface gate brain entry of blood-borne signals and thus food intake.

Diabetes complications are attributed to reactive by-products of glycolysis, but cells consuming lactate and pyruvate are not spared. Here, the authors show that the reactive dicarbonyl dimethylglyoxal is formed from pyruvate, rises in diabetes, and potentially causes neurological complications of diabetes.

Alzheimer disease has a sex bias: women are twice as likely as men to be affected. Studies have linked elevated follicle-stimulating hormone (FSH) levels to worsened Alzheimer disease pathology and cognitive decline in mice. Exploring the interaction of FSH with APOE4 has uncovered new aspects of Alzheimer disease. The therapeutic potential of FSH and gonadotropin-releasing hormone have also been highlighted.

Studying GnRH neuroendocrine cells in the mouse olfactory bulb (GnRH^OB neurons), Decoster et al. show that these cells respond to female odors and their activation regulates males’ female-odor preference and mating behavior.

Ependymal cell cilia regulate cerebrospinal fluid flow through the cerebral ventricles. Here the authors show that the metabolic peptide melanin-concentrating hormone (MCH) increases cilia beat frequency in the third ventricle, and a lack of the MCH receptor increases ventricle size.

Gonadotropin-releasing hormone is implicated in cognitive functions, and its loss is a factor in pathological brain ageing. There are similarities between these processes and the neurological and cognitive deficits observed in patients with long COVID. Here, we explore the hypothesis that neuroanatomical and transcriptomic alterations associated with long COVID could stem from this neuroendocrine perturbation.

Extended exposure to breastfeeding in rodent pups protects them from diet-induced obesity in adulthood by increasing thermogenesis and energy expenditure. This is mediated by liver-derived FGF21 signalling to the lateral hypothalamic area.

In response to acute thermal challenge, thermosensing glutamatergic neurons of the parabrachial nucleus in mouse brain activate tanycytes, which reduce the excitability of Flt1-expressing dopamine and agouti-related peptide-containing neurons, thus suppressing appetite.

Mate preference and copulatory behavior in female rodents are coordinated with the ovulation cycles of the animal. This study shows that hypothalamic kisspeptin neurons control both mate choice and copulation, and therefore, that sexual behavior and ovulation may be synchronized by the same neuropeptide.

Delval, Hantute-Ghesquier, Sencio and colleagues demonstrate that depletion of age-associated senescent cells decreases pulmonary viral load and ameliorates early and late lung COVID-19 in a hamster model of aging.

Kiss1 neurons are essential for puberty and fertility. Here, the authors show that canonical microRNA biosynthesis in Kiss1 neurons plays an essential role in the control of puberty and fertility, especially in females, likely via repression of repressors on the Kiss1 gene.

A novel study led by scientists in Lübeck, Germany, shows that SARS-CoV-2-infected brain endothelial cells undergo cell death due to the cleavage of NEMO by the viral protease M^pro, potentially causing cerebral COVID-19 and ‘long COVID’ symptoms.

Food odour recognition is involved in the food anticipatory response. A study in Nature Metabolism describes how the olfactory system differentially regulates metabolic adaptations depending on energy availability. These effects are mediated by a brain circuit involving the melanocortin system that controls systemic lipid utilization via the sympathetic nervous system.

Folgueira et al. show that dopamine signalling in the lateral hypothalamic area and the zona incerta reduces body weight and increases energy expenditure by increasing brown adipose tissue thermogenesis in rodents. Weight loss and increased energy expenditure were also observed in patients treated with a dopamine receptor 2 agonist.

Anti-Müllerian hormone (AMH) plays a role in sexual differentiation and gonadal function, but extra-gonadal effects of AMH are not known. Here Cimino et al. show that AMH activates a subset of gonadotrophin-releasing hormone (GnRH)-releasing neurons, contributing to luteinizing hormone secretion from the pituitary gland.

Transforming growth factor-β (TGFβ) regulates many cellular processes. Here the authors show that the orphan G-protein coupled receptor GPR50 can activate the TGFβ receptor I, in the absence of TGFβ, by stabilizing its active conformation and show antitumor activity in a mouse model of breast cancer.

Excess anti-Müllerian hormone during pregnancy results in polycystic ovary syndrome-like phenotypes in female offspring, possibly explaining its pathogenesis as well as suggesting a possible therapy.

Tumorigenesis is a complex process driven by numerous risk factors. Here, genomic analysis of liver cancer reveals the evolution of mutational signatures during tumor development, highlighting mutational and structural signatures linked to environmental exposures and endogenous cellular processes.

Congenital hypogonadotropic hypogonadism (CHH)—a rare disorder caused by deficient production, secretion or action of gonadotropin-releasing hormone—results in an absence of puberty and infertility. Here, Ulrich Boehm and colleagues summarize approaches for the diagnosis and treatment of CHH in light of recent discoveries. This Consensus Statement differs from existing guidelines for the treatment of hypogonadism as it focuses exclusively on CHH.

Nampoothiri et al. discuss the most recent literature that places glial cells as key mediators of energy balance through integration of peripheral signals in discrete brain regions, highlighting the relevance of glia in the pathophysiology of metabolic diseases.

Melanin-concentrating hormone (MCH) integrates physiological functions and mood states associated with energy and glucose homeostasis. In this Review, Al-Massadi et al. describe how MCH regulates the hedonic component of food intake and discuss its potential as a therapeutic target.

Key papers on the role of nutrition and metabolic cues in puberty timing were published in 1963, and there have been many advances in this field in the subsequent 60 years. This Review discusses the latest advances in basic and translational sciences underlying the nutritional and metabolic control of pubertal development.

Knowledge of the role of glial–neuronal interactions in the physiology of food intake and energy metabolism is emerging. This review highlights the role of astrocytes, microglia, and tanycytes in central control of systemic metabolism.

SARS-CoV-2 pseudovirus infects human hepatocytes leading to metabolic reprogramming towards glycolysis and impaired mitochondrial activity, and metformin can reduce infection under steatotic conditions.