Metabolic actions of the growth hormone-insulin growth factor-1 axis and its interaction with the central nervous system

Al‐Massadi, Omar; Parini, Paolo; Fernø, Johan; Luquet, Serge; Quiñones, Mar

doi:10.1007/s11154-022-09732-x

Cited by 8 publications

(4 citation statements)

References 133 publications

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“…Alternatively, the human hepatocytes can also respond to these signals in a different manner that does not result in the rhythmic activation of the mTOR pathway. The inappropriate response of human hepatocytes to mouse signals is also illustrated by the blunted response to Growth Hormone (GH), an important regulator of the sex biased liver function and metabolism (Al-Massadi et al, 2022; Lichanska and Waters, 2008). Indeed, endogenous mouse GH is high while IGF-1 is low in LHM ( Figure S1G ).…”

Section: Resultsmentioning

confidence: 99%

Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in rhythmic behavior and physiology

Delbès¹,

Quiñones²,

Gobet³

et al. 2022

Preprint

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The circadian clock is an evolutionarily acquired gene network that synchronizes physiological processes to adapt homeostasis to the succession of day and night. While most mammalian cells have a circadian clock, their synchronization at the body-level depends on a central pacemaker located in the suprachiasmatic nuclei of the hypothalamus that integrates light signals. However, peripheral organs are also synchronized by feeding cues that can uncoupled them from the central pacemaker. Nevertheless, the potential feedback of peripheral signals on the central clock remains poorly characterized. To discover whether peripheral organ circadian clocks may affect the central pacemaker, we used a chimeric model in which mouse hepatocytes were replaced by human hepatocytes. These human hepatocytes showed a specific rhythmic physiology caused by their blunted response to mouse systemic signals. Strikingly, mouse liver humanization reprogrammed the liver diurnal gene expression and modified the phase of the circadian clock. The phase advance was also reflected in the muscle as well as the entire rhythmic physiology of the animals, indicating an impact on the circadian function of the central clock. Like mice with a deficient central clock, the humanized animals shifted their rhythmic physiology more rapidly to the light phase under day feeding. Our results indicate that peripheral clocks may affect the central pacemaker and offer new perspectives to understand the impact of peripheral clocks on the global circadian physiology.

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Section: Resultsmentioning

confidence: 99%

Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in rhythmic behavior and physiology

Delbès¹,

Quiñones²,

Gobet³

et al. 2022

Preprint

Self Cite

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“…Several possible explanations have been proposed. Firstly, many obesity-related factors, such as insulin resistance, glucose homeostasis, and chronic in ammation, affect the GH/IGF-1 axis, leading to GH resistance and reducing circulating IGF-1 levels [29][30][31][32] . Secondly, hyperinsulinemia combined with obesity may down-regulate the expression level of IGF-1 binding proteins (IGF-BPs) and inhibit circulating IGF-1 through negative feedback regulation 33 .In addition, Bann et al 34 and Savastano al.…”

Section: Discussionmentioning

confidence: 99%

Non-linear causal association of body mass index with serum insulin-like growth factor 1: A Mendelian randomization study

Pei,

Song,

et al. 2023

Preprint

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Objectives: Insulin-like growth factor1 (IGF-1) is a polypeptide hormone mainly secreted from the liver. The synthesis and secretion of IGF-1 are affected by various factors including unusual body weight. Nonetheless, the causal relationship between body mass index (BMI) and IGF-1 is still under debate from existing epidemiological studies, implying their complicated regulation pattern. Aiming to investigate their causal association, we conducted a large-scale linear and non-linear Mendelian randomization (MR) analysis in the UK Biobank (UKB) cohort with BMI as the exposure and IGF-1 as the outcome. Methods: After applying a series of exclusion criteria and covariate adjustment, a total of 244 991 participants from the UKB were eligible for analysis. The polygenic risk score (PRS) of BMI was constructed on 96 instrumental variables (IVs). The non-linear observational association between BMI and IGF-1 was examined by a restricted cubic spline test. Non-linear MR analysis was performed with the piecewise linear method and verified by doubly-ranked stratification and log-transformation methods. In addition to combined analysis, stratified analysis was performed by sex and age groups. A series of sensitivity analyses were performed to examine the robustness of the results. Results: Restricted cubic spline regression demonstrated an inverted U-shaped association between BMI and IGF-1 (P non-linear<0.001), which was also supported by MR analysis (Quadratic P-value: 4.93×10-6, Cochran Q P-value: 2.94×10-5). Specifically, genetically predicted BMI was significantly positively correlated with IGF-1 levels when BMI was less than 25kg/m2, and genetically predicted BMI was significantly negatively correlated with IGF-1 levels when BMI exceeded around 28kg/m2. Stratified analysis showed no difference against sex and different age groups. Sensitivity analyses gave similar results, demonstrating the robustness of the results. Conclusions: This study suggested a non-linear causal relationship between BMI and IGF-1 and this effect may not influenced by sex and age.

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“…Regulated by hypothalamic secretion of GH-releasing hormone (GHRH), GH is a bone regulatory factor produced by the anterior pituitary gland that exerts a positive influence on bone mass. Numerous studies have demonstrated that GH primarily acts through the release of insulin-like growth factor 1 (IGF-1) [ 72 – 74 ], which bind to glycoprotein-coupled receptors on osteoblasts, thereby promoting osteoblast proliferation [ 50 , 73 ]. FSH, a major regulator of sex hormone secretion, is regulated by the hypothalamic secretion of gonadotropin-releasing hormone (GnRH).…”

Section: Bone-organ Axesmentioning

confidence: 99%

Bone-organ axes: bidirectional crosstalk

Deng,

Wang,

Wang

et al. 2024

Military Med Res

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In addition to its recognized role in providing structural support, bone plays a crucial role in maintaining the functionality and balance of various organs by secreting specific cytokines (also known as osteokines). This reciprocal influence extends to these organs modulating bone homeostasis and development, although this aspect has yet to be systematically reviewed. This review aims to elucidate this bidirectional crosstalk, with a particular focus on the role of osteokines. Additionally, it presents a unique compilation of evidence highlighting the critical function of extracellular vesicles (EVs) within bone-organ axes for the first time. Moreover, it explores the implications of this crosstalk for designing and implementing bone-on-chips and assembloids, underscoring the importance of comprehending these interactions for advancing physiologically relevant in vitro models. Consequently, this review establishes a robust theoretical foundation for preventing, diagnosing, and treating diseases related to the bone-organ axis from the perspective of cytokines, EVs, hormones, and metabolites.

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Metabolic actions of the growth hormone-insulin growth factor-1 axis and its interaction with the central nervous system

Cited by 8 publications

References 133 publications

Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in rhythmic behavior and physiology

Mice with humanized livers reveal the involvement of hepatocyte circadian clocks in rhythmic behavior and physiology

Non-linear causal association of body mass index with serum insulin-like growth factor 1: A Mendelian randomization study

Bone-organ axes: bidirectional crosstalk

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