Is there a causal relationship between obesity and puberty?

The Lancet Child & Adolescent Health, Journal Year: 2018, Volume and Issue: 3(1), P. 44 - 54

Published: Nov. 14, 2018

Language: Английский

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Metabolic regulation of kisspeptin — the link between energy balance and reproduction

Nature Reviews Endocrinology, Journal Year: 2020, Volume and Issue: 16(8), P. 407 - 420

Published: May 19, 2020

Language: Английский

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Obesity, Neuroinflammation, and Reproductive Function

Endocrinology, Journal Year: 2019, Volume and Issue: 160(11), P. 2719 - 2736

Published: Sept. 12, 2019

Abstract The increasing occurrence of obesity has become a significant public health concern. Individuals with have higher prevalence heart disease, stroke, osteoarthritis, diabetes, and reproductive disorders. Reproductive problems include menstrual irregularities, pregnancy complications, infertility due to anovulation, in women, lower testosterone diminished sperm count, men. In particular, women reduced levels both gonadotropin hormones, and, obese men, is accompanied by LH. Taken together, these findings indicate central dysregulation the hypothalamic–pituitary–gonadal axis, specifically at level GnRH neuron function, which final brain output for regulation reproduction. Obesity state hyperinsulinemia, hyperlipidemia, hyperleptinemia, chronic inflammation. Herein, we review recent advances our understanding how metabolic immune changes affect hypothalamic function neurons. latter part, focus on neuroinflammation as major consequence discuss that reveal neurons are uniquely positioned respond inflammatory changes.

Language: Английский

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Hypogonadism and male obesity: Focus on unresolved questions

Clinical Endocrinology, Journal Year: 2018, Volume and Issue: 89(1), P. 11 - 21

Published: April 23, 2018

Summary Obesity, increasing in prevalence globally, is the clinical condition most strongly associated with lowered testosterone concentrations men and presents as one of strongest predictors receiving treatment. While low circulating total modest obesity primarily reflect reduced sex hormone binding globulin, more marked can lead to genuine hypothalamic‐pituitary‐testicular axis ( HPT ) suppression. suppression likely mediated via pro‐inflammatory cytokine dysregulated leptin signalling aggravated by comorbidities. Whether oestradiol‐mediated negative hypothalamic‐pituitary feedback plays a pathogenic role requires further study. Although obesity‐hypogonadism relationship bidirectional, effects on are substantial than adiposity. In markedly obese submitted bariatric surgery, weight loss very effective reactivating axis. contrast, lifestyle measures less reducing generally only increases testosterone. randomized controlled trials RCT s), treatment does not reduce body weight, but modestly reduces fat mass muscle mass. Short‐term studies have shown that carefully selected may benefits symptoms androgen deficiency composition even additive diet alone. However, longer term, larger s designed for patient‐important outcomes potential risks required. Until such available, cannot be routinely recommended obesity‐associated nonclassical hypogonadism. Lifestyle or where indicated surgery achieve loss, optimization comorbidities remain first line.

Language: Английский

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Novel mechanisms for the metabolic control of puberty: implications for pubertal alterations in early-onset obesity and malnutrition

Journal of Endocrinology, Journal Year: 2019, Volume and Issue: 242(2), P. R51 - R65

Published: June 10, 2019

Puberty is driven by sophisticated neuroendocrine networks that timely activate the brain centers governing reproductive axis. The timing of puberty genetically determined; yet, also sensitive to numerous internal and external cues, among which metabolic/nutritional signals are especially prominent. Compelling epidemiological evidence suggests alterations age becoming more frequent; underlying mechanisms remain largely unknown, but escalating prevalence obesity other metabolic/feeding disorders possibly a major contributing factor. This phenomenon may have clinical implications, since in pubertal been associated adverse health outcomes, including higher risk earlier all-cause mortality. urges for better understanding neurohormonal basis normal its deviations. has recently documented master role hypothalamic neurons producing kisspeptins, encoded Kiss1, pathways controlling puberty. Kiss1 seemingly participate transmitting regulatory actions metabolic cues on maturation. Key cellular sensors, as mammalian target rapamycin (mTOR), AMP-activated protein kinase (AMPK) fuel-sensing deacetylase, SIRT1, shown modulation Recently, we AMPK SIRT1 operate molecular effectors control and, thereby, onset. Alterations these contribute perturbation linked conditions stress humans, such subnutrition or might become druggable targets management disorders.

Language: Английский

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Nitric oxide signalling in the brain and its control of bodily functions

British Journal of Pharmacology, Journal Year: 2019, Volume and Issue: 177(24), P. 5437 - 5458

Published: July 26, 2019

Nitric oxide (NO) is a versatile molecule that plays key roles in the development and survival of mammalian species by endowing brain neuronal networks with ability to make continual adjustments function response moment‐to‐moment changes physiological input. Here, we summarize progress field argue NO‐synthetizing neurons NO signalling provide core hub for integrating sensory‐ homeostatic‐related cues, control bodily functions, potential target new therapeutic opportunities against several neuroendocrine behavioural abnormalities.

Language: Английский

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The effect of excess body fat on female and male reproduction

Metabolism, Journal Year: 2020, Volume and Issue: 107, P. 154193 - 154193

Published: Feb. 29, 2020

Language: Английский

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Childhood obesity and central precocious puberty

Frontiers in Endocrinology, Journal Year: 2022, Volume and Issue: 13

Published: Nov. 18, 2022

Childhood obesity is a major public health problem worldwide, and the relationship between central precocious puberty has long been confirmed, however, mechanisms underlying this association remain elusive. This review provides an overview of recent progress regarding how childhood impacts on hypothalamic-pituitary-gonadal axis pubertal onset, focusing adipokines (leptin ghrelin), hormone (insulin), lipid (ceramide), as well critical signaling pathways (AMPK/SIRT, mTOR) that integrate peripheral metabolism circuits. Notably, prevention CPP beneficial for adult life children, thus we further summarize potential strategies in treating preventing CPP. The updated understanding metabolic stress pediatric endocrine disease will arise attention society, also contribute to more serious comorbidities later period children.

Language: Английский

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Kisspeptins and the neuroendocrine control of reproduction: Recent progress and new frontiers in kisspeptin research

Frontiers in Neuroendocrinology, Journal Year: 2022, Volume and Issue: 65, P. 100977 - 100977

Published: Jan. 7, 2022

In late 2003, a major breakthrough in our understanding of the mechanisms that govern reproduction occurred with identification reproductive roles kisspeptins, encoded by Kiss1 gene, and their receptor, Gpr54 (aka, Kiss1R). The discovery this unsuspected facet attracted an extraordinary interest boosted intense research activity, human model species, that, relatively short period, established series basic concepts on physiological kisspeptins. Such fundamental knowledge, gathered these early years kisspeptin research, set scene for more recent in-depth dissection intimacies neuronal networks involving neurons, precise regulation molecular underpinnings function kisspeptins as pivotal regulators all key aspects function, from puberty onset to pulsatile gonadotropin secretion metabolic control fertility. While no clear temporal boundaries between two periods can be defined, review we will summarize most prominent advances last ten years, means provide up-dated view state art potential paths future progress dynamic, ever growing domain Neuroendocrinology.

Language: Английский

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Early programming of reproductive health and fertility: novel neuroendocrine mechanisms and implications in reproductive medicine

Human Reproduction Update, Journal Year: 2022, Volume and Issue: 28(3), P. 346 - 375

Published: Jan. 25, 2022

Abstract BACKGROUND According to the Developmental Origins of Health and Disease (DOHaD) hypothesis, environmental changes taking place during early maturational periods may alter normal development predispose occurrence diverse pathologies later in life. Indeed, adverse conditions these critical developmental windows high plasticity have been reported offspring trajectory, causing permanent functional structural perturbations that long term enhance disease susceptibility. However, while solid evidence has documented fluctuations factors, ranging from nutrient availability chemicals, stages (including peri-conceptional period) discernible programming effects increase vulnerability develop metabolic perturbations, impact eventual mechanisms involved, such alterations on reproductive phenotype received less attention. OBJECTIVE AND RATIONALE This review will summarize recent advances basic clinical research support concept DOHaD context nutritional hormonal occurring periconceptional, fetal postnatal stages, different aspects function both sexes. Special emphasis be given stress timing puberty adult gonadotropic function, address underlying neuroendocrine pathways, with particular attention involvement Kiss1 system perturbations. The implications phenomena terms medicine also considered. SEARCH METHODS A comprehensive MEDLINE search, using PubMed as main interface, articles reviews, published mainly between 2006 2021, carried out. Search was implemented multiple terms, focusing preclinical data studies, addressing gestational perinatal reproduction. Selected studies considered, when relevant. OUTCOMES body evidence, prenatal pubertal maturation, well fertility. Furthermore, exposure bisphenol A, maternal shown negatively influence adulthood. pathways involved addressed, by which identified an, yet incomplete, array molecular neurohormonal effectors. These include, prominently, epigenetic regulatory hypothalamic system, likely contribute generation and/or stress. In addition other major regulators GnRH neurosecretion, γ-aminobutyric acid glutamate, targets programming. WIDER IMPLICATIONS addresses an underdeveloped area biology help improve our understanding human disorders stresses importance, pathogenic impact, determinants puberty,

Language: Английский

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