Obesity Hypertension: Pathophysiological Role of Leptin in Neuroendocrine Dysregulation

Go, Orson; Liu, Kan; Villarreal, Daniel; Spear, Robert M.; Freeman, Ronald H.; Reams, Garry P.; Weber, Karl T.

doi:10.1097/maj.0b013e31827ad5cf

Cited by 4 publications

(4 citation statements)

References 47 publications

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“…This should also contribute to sound, scientifically-based policies and decisions (e.g., as advocated by (Gore et al, 2013)) regarding the emerging environmental and human health problems resulting from specific disruption of neuroendocrine control systems. This is imperative as evidence grows for associations between environmental contaminant exposures and diseases having strong neuroendocrine components, for example, reduced fertility, obesity, neurodegeneration and cardiac disease, among other conditions (Bellavance and Rivest, 2012; Carro et al, 2013; Go et al, 2013; Straub et al, 2013). Here we outline specific examples of neuroendocrine disruption by various chemicals and highlight some key concepts.…”

Section: Introductionmentioning

confidence: 99%

Current concepts in neuroendocrine disruption

León-Olea

Martyniuk

Orlando

et al. 2014

General and Comparative Endocrinology

127

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In the last few years, it has become clear that a wide variety of environmental contaminants have specific effects on neuroendocrine systems in fish, amphibians, birds and mammals. While it is beyond the scope of this review to provide a comprehensive examination of all of these neuroendocrine disruptors, we will focus on select representative examples. Organochlorine pesticides bioaccumulate in neuroendocrine areas of the brain that directly regulate GnRH neurons, thereby altering the expression of genes downstream of GnRH signaling. Organochlorine pesticides can also agonize or antagonize hormone receptors, adversely affecting crosstalk between neurotransmitter systems. The impacts of polychlorinated biphenyls are varied and in many cases subtle. This is particularly true for neuroedocrine and behavioral effects of exposure. These effects impact sexual differentiation of the hypothalamic-pituitary-gonadal axis, and other neuroendocrine systems regulating the thyroid, metabolic, and stress axes and their physiological responses. Weakly estrogenic and anti-androgenic pollutants such as bisphenol A, phthalates, phytochemicals, and the fungicide vinclozolin can lead to severe and widespread neuroendocrine disruptions in discrete brain regions, including the hippocampus, amygdala, and hypothalamus, resulting in behavioral changes in a wide range of species. Behavioral features that have been shown to be affected by one or more these chemicals include cognitive deficits, heightened anxiety or anxiety-like, sociosexual, locomotor, and appetitive behaviors. Neuroactive pharmaceuticals are now widely detected in aquatic environments and water supplies through the release of wastewater treatment plant effluents. The antidepressant fluoxetine is one such pharmaceutical neuroendocrine disruptor. Fluoxetine is a selective serotonin reuptake inhibitor that can affect multiple neuroendocrine pathways and behavioral circuits, including disruptive effects on reproduction and feeding in fish. There is growing evidence for the association between environmental contaminant exposures and diseases with strong neuroendocrine components, for example decreased fecundity, neurodegeneration, and cardiac disease. It is critical to consider the timing of exposures of neuroendocrine disruptors because embryonic stages of central nervous system development are exquisitely sensitive to adverse effects. There is also evidence for epigenetic and transgenerational neuroendocrine disrupting effects of some pollutants. We must now consider the impacts of neuroendocrine disruptors on reproduction, development, growth and behaviors, and the population consequences for evolutionary change in an increasingly contaminated world. This review examines the evidence to date that various so-called neuroendocrine disruptors can induce such effects often at environmentally-relevant concentrations.

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Section: Introductionmentioning

confidence: 99%

Current concepts in neuroendocrine disruption

León-Olea

Martyniuk

Orlando

et al. 2014

General and Comparative Endocrinology

127

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“…It has central roles in the energy expenditure, food intake, many reproductive processes, regulation of energy homeostasis, neuroendocrine function, and metabolism (Kelesidis et al, 2010). Beside the synthesis by adipose tissue as the main source (Go et al, 2013), there have been indentified other sources of leptin in the body including testicles (Soyupek et al, 2005), ovaries (Löffler et al, 2001), placenta (Maymó et al, 2011), cartilage and bone cells (Morroni et al, 2004), skeletal muscle (Solberg et al, 2005) and stomach (Mix et al, 2004). Furthermore, the mitogenic, transforming or migration-induced properties of leptin have been revealed in many different cell types such as smooth muscle cells (Oda et al, 2001), normal and neoplastic colon cells (Hardwick et al, 2001;Liu et al, 2001); and also normal and malignant mammary epithelial cells (Dieudonne et al, 2002;Laud et al, 2002).…”

Section: Introductionmentioning

confidence: 99%

“…Many factors contribute to breast cancer development that one documented risk factor is leptin (García-Robles et al, 2013). Leptin, a 167 protein with a molecular mass of 16 kDa, expressed mainly by adipose tissues (Go et al, 2013). It has central roles in the energy expenditure, food intake, many reproductive processes, regulation of energy homeostasis, neuroendocrine function, and metabolism (Kelesidis et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

Inhibition of Leptin and Leptin Receptor Gene Expression by Silibinin-Curcumin Combination

Nejati-Koshki¹,

Akbarzadeh²,

Pourhasan-Moghaddam³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Leptin and its receptor are involved in breast carcinogenesis as mitogenic factors. Therefore, they could be considered as targets for breast cancer therapy. Expression of the leptin receptor gene could be modulated by leptin secretion. Silibinin and curcumin are herbal compounds with anti-cancer activity against breast cancer. The aim of this study was to assess their potential to inhibit of expression of the leptin gene and its receptor and leptin secretion. Cytotoxic effects of the two agents on combination on T47D breast cancer cells was investigated by MTT assay test after 24h treatment. With different concentrations the levels of leptin, leptin receptor genes expression were measured by reverse-transcription real-time PCR. Amount of secreted leptin in the culture medium was determined by ELISA. Data were statistically analyzed by one-way ANOVA test. The silibinin and curcumin combination inhibited growth of T47D cells in a dose dependent manner. There were also significant difference between control and treated cells in leptin expression and the quantity of secreted leptin with a relative decrease in leptin receptor expression. In conclusion, these herbal compounds inhibit the expression and secretion of leptin and it could probably be used as drug candidates for breast cancer therapy through leptin targeting in the future.

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“…This brings about a biomechanical imbalance, ultimately manifesting in clinical symptoms. The release of adipocyte factors, notably leptin and adiponectin, plays a critical role in driving the metabolic changes and in ammatory responses associated with disc degeneration [12,13]. Furthermore, obesity is linked to signi cantly elevated levels of IL-6 and pro-in ammatory cascades throughout the body, contributing to the in ammation-mediated pathway of disc degeneration [14].…”

Section: Introductionmentioning

confidence: 99%

Causal relationship between trunk and lower limb fat mass and interver tebral disc disorders: A two-sample mendelian randomization study

Huang,

Tian,

Tian

et al. 2024

Preprint

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Background: Intervertebral disc disorders (IVDDs) represent a significant cause of disability worldwide, with their etiology being multifactorial, including genetic predispositions and lifestyle factors such as obesity. The significance of body fat distribution in the onset of intervertebral disc disorders (IVDDs) has been recognized, yet the causal relationship remains poorly understood. This study aimed to elucidate the genetic underpinnings of this relationship by investigating the association between fat mass distribution in the trunk and low limb and the risk of IVDDs using Mendelian randomization (MR). Methods: A comprehensive analysis was conducted using single nucleotide polymorphisms (SNPs) as instrumental variables to assess the genetic predispositions to increased fat mass in specific body regions (trunk and low limb) and their associations with IVDDs. The study began with reading 9,851,866 SNPs for trunk and low limb fat mass and 21,304,570 SNPs for IVDDs. Through a series of data cleaning steps, including linkage disequilibrium clumping, SNP merging, allele harmonization, and checks against the Phenoscanner database for confounding factors, the number of relevant SNPs was reduced to 353 for trunk fat mass, and 346 and 337 for left and right leg fat mass, respectively. The final causal analysis was performed using the inverse variance weighted (IVW) method and MR-Egger method, along with sensitivity analysis to test the robustness of the findings. Results: The IVW method demonstrated a significant positive causal relationship between trunk fat mass and IVDDs (OR = 1.274, 95% CI: 1.186-1.368, p < 0.001), while the MR-Egger method showed no statistical significance (p = 0.214). However, both methods revealed a consistent and statistically significant association for low limb fat mass with IVDDs. Specifically, the IVW method indicated OR of 1.461 (95% CI: 1.330-1.605, p < 0.001) for left leg fat mass and 1.467 (95% CI: 1.331-1.618, p < 0.001) for right leg fat mass. The presence of heterogeneity and potential pleiotropy was assessed, with findings supporting the stability and reliability of the causal inferences. Conclusion: This study confirmed a positive causal relationship between trunk and lower limb fat mass and the risk of IVDDs, highlighting the importance of considering body fat distribution in the prevention and management of IVDDs. The findings suggested that interventions aimed at reducing trunk and lower limb fat mass could potentially lower the risk of developing IVDDs. This research added valuable insights into the genetic and physiological links between body fat distribution and IVDDs, paving the way for targeted preventive strategies and therapeutic interventions.

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Obesity Hypertension: Pathophysiological Role of Leptin in Neuroendocrine Dysregulation

Cited by 4 publications

References 47 publications

Current concepts in neuroendocrine disruption

Current concepts in neuroendocrine disruption

Inhibition of Leptin and Leptin Receptor Gene Expression by Silibinin-Curcumin Combination

Causal relationship between trunk and lower limb fat mass and interver tebral disc disorders: A two-sample mendelian randomization study

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