The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity

Martínez-Sánchez, Noelia; Sweeney, Owen; Sidarta-Oliveira, Davi; Caron, Alexandre; Stanley, Sarah A.; Domingos, Ana I.

doi:10.1016/j.neuron.2022.10.017

Cited by 34 publications

(20 citation statements)

References 277 publications

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“…There is abundant neuronal crosstalk between peripheral organs and the brain. The sympathetic nervous system (SNS) affects metabolic homeostasis by influencing the activity and function of several tissues and organs including skeletal muscle, liver and adipose tissue [82,83]. There is some evidence that overfeeding has a modest effect on the activity of the SNS, but this is not corroborated by studies measuring catecholamine excretion in urine [2].…”

Section: Non-endocrine Defence Systems Against Weight Gainmentioning

confidence: 99%

Physiological protection against weight gain: evidence from overfeeding studies and future directions

Lund

Clemmensen

2023

Phil. Trans. R. Soc. B

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Body weight is under physiological regulation. When body fat mass decreases, a series of responses are triggered to promote weight regain by increasing food intake and decreasing energy expenditure. Analogous, in response to experimental overfeeding, excessive weight gain is counteracted by a reduction in food intake and possibly by an increase in energy expenditure. While low blood leptin and other hormones defend against weight loss, the signals that oppose overfeeding-induced fat mass expansion are still unknown. In this article, we discuss insights gained from overfeeding interventions in humans and intragastric overfeeding studies in rodents. We summarize the knowledge on the relative contributions of energy intake, energy expenditure and energy excretion to the physiological defence against overfeeding-induced weight gain. Furthermore, we explore literature supporting the existence of unidentified endocrine and non-endocrine pathways that defend against weight gain. Finally, we discuss the physiological drivers of constitutional thinness and suggest that overfeeding of individuals with constitutional thinness represents a gateway to understand the physiology of weight gain resistance in humans. Experimental overfeeding, combined with modern multi-omics techniques, has the potential to unveil the long-sought signalling pathways that protect against weight gain. Discovering these mechanisms could give rise to new treatments for obesity. This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.

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Section: Non-endocrine Defence Systems Against Weight Gainmentioning

confidence: 99%

Physiological protection against weight gain: evidence from overfeeding studies and future directions

Lund

Clemmensen

2023

Phil. Trans. R. Soc. B

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“…In particular, two independent studies used immunolabeling‐enabled three‐dimensional imaging of solvent‐cleared organs plus (iDisco+), and convincingly concluded that neural innervations within the liver are exclusively of sympathetic nature (Adori et al, 2021; Liu et al, 2021). This suggests that the vagus control of liver metabolism may occur through indirect effects, such as alterations of portal blood flow or by modulating the sympathetic nervous system (Bockx et al, 2012; Martinez‐Sanchez et al, 2022). Nevertheless, the work from Kwon and colleagues is consistent with the study from Üner and colleagues, reporting that chronic inhibition of ARC POMC neurons lowers blood glucose (Üner et al, 2019).…”

Section: Leptin Regulates Glucose Homeostasis Through Direct Actions ...mentioning

confidence: 99%

A critical update on the leptin‐melanocortin system

Lavoie

Michael

Caron

2023

Journal of Neurochemistry

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“…These factors, such as nerve growth factor (NGF) and brain‐derived neurotrophic factor (BDNF) can influence the development and plasticity of WAT nerves, supporting their growth and establishing connections. [ 14,121d,129 ]…”

Section: The Sympathetic Innervation and Immune Milieu In Adipose Tis...mentioning

confidence: 99%

“…By employing tissue‐clearing methods, researchers have successfully detected nerve bundles throughout the iWAT, visualizing the complete axonal tree of sympathetic neurons in situ. [ 14,123c,d,129c ] Catecholaminergic reporter mice labeled with lipophilic dye and analyzed using two‐photon microscopy revealed that sympathetic nerves innervate fat pads and bouton‐like structures were found to innervate around 8% of adipocytes. [ 123e ]…”

Section: The Sympathetic Innervation and Immune Milieu In Adipose Tis...mentioning

confidence: 99%

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The Sympathetic‐Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues

Ren,

Hua,

Cao

et al. 2023

Advanced Science

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Sympathetic innervation plays a crucial role in maintaining energy balance and contributes to metabolic pathophysiology. Recent evidence has begun to uncover the innervation landscape of sympathetic projections and sheds light on their important functions in metabolic activities. Additionally, the immune system has long been studied for its essential roles in metabolic health and diseases. In this review, the aim is to provide an overview of the current research progress on the sympathetic regulation of key metabolic organs, including the pancreas, liver, intestine, and adipose tissues. In particular, efforts are made to highlight the critical roles of the peripheral nervous system and its potential interplay with immune components. Overall, it is hoped to underscore the importance of studying metabolic organs from a comprehensive and interconnected perspective, which will provide valuable insights into the complex mechanisms underlying metabolic regulation and may lead to novel therapeutic strategies for metabolic diseases.

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The sympathetic nervous system in the 21st century: Neuroimmune interactions in metabolic homeostasis and obesity

Cited by 34 publications

References 277 publications

Physiological protection against weight gain: evidence from overfeeding studies and future directions

Physiological protection against weight gain: evidence from overfeeding studies and future directions

A critical update on the leptin‐melanocortin system

The Sympathetic‐Immune Milieu in Metabolic Health and Diseases: Insights from Pancreas, Liver, Intestine, and Adipose Tissues

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