Carotid Body and Metabolic Syndrome: Mechanisms and Potential Therapeutic Targets

Kim, Lenise Jihe; Polotsky, Vsevolod Y.

doi:10.3390/ijms21145117

Cited by 15 publications

(18 citation statements)

References 218 publications

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“…2 ) (see e.g. (Kim and Polotsky 2020 ; Sacramento et al 2020 )). Leptin receptors are present in type I cells of mice, rat and human CBs (Caballero-Eraso et al 2019 ; Messenger et al 2012 ; Porzionato et al 2011 ; Ribeiro et al 2018 ).…”

Section: The Carotid Body As a New Player In The Link Between Immunitmentioning

confidence: 98%

Immunity and the carotid body: implications for metabolic diseases

2020

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Neuro-immune communication has gained enormous interest in recent years due to increasing knowledge of the way in which the brain coordinates functional alterations in inflammatory and autoimmune responses, and the mechanisms of neuron-immune cell interactions in the context of metabolic diseases such as obesity and type 2 diabetes. In this review, we will explain how this relationship between the nervous and immune system impacts the pro- and anti-inflammatory pathways with specific reference to the hypothalamus-pituitary-adrenal gland axis and the vagal reflex and will explore the possible involvement of the carotid body (CB) in the neural control of inflammation. We will also highlight the mechanisms of vagal anti-inflammatory reflex control of immunity and metabolism, and the consequences of functional disarrangement of this reflex in settlement and development of metabolic diseases, with special attention to obesity and type 2 diabetes. Additionally, the role of CB in the interplay between metabolism and immune responses will be discussed, with specific reference to the different stimuli that promote CB activation and the balance between sympathetic and parasympathetic in this context. In doing so, we clarify the multivarious neuronal reflexes that coordinate tissue-specific responses (gut, pancreas, adipose tissue and liver) critical to metabolic control, and metabolic disease settlement and development. In the final section, we will summarize how electrical modulation of the carotid sinus nerve may be utilized to adjust these reflex responses and thus control inflammation and metabolic diseases, envisioning new therapeutics horizons.

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Section: The Carotid Body As a New Player In The Link Between Immunitmentioning

confidence: 98%

Immunity and the carotid body: implications for metabolic diseases

2020

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“…Carotid bodies are indeed sensitive to glucose ( Pardal and López-Barneo, 2002 ) and metabolic signals and also to inflammatory signals since insulin, leptin, and pro-inflammatory cytokines activate the carotid bodies, inducing a sympathetic overactivation that leads to glucose intolerance and insulin insensitivity ( Sacramento et al, 2020 ). The carotid body-induced sympathetic overactivation may thus underlie metabolic syndrome and systemic hypertension ( Kim and Polotsky, 2020 ) and justify carotid body denervation or pharmacological targeting as possible therapies ( Lastra et al, 2014 ; Pijacka et al, 2016 ; Sacramento et al, 2017 ). These, however, are not without risk, given the relevance of carotid bodies in the response to acute hypoxia and hypercapnia in particular in hypertensive subjects ( Conde, 2018 ).…”

Section: Introductionmentioning

confidence: 99%

Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases

Caretta

Mucignat-Caretta

2022

Front. Neural Circuits

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Chemosensory systems are deemed marginal in human pathology. In appraising their role, we aim at suggesting a paradigm shift based on the available clinical and experimental data that will be discussed. Taste and olfaction are polymodal sensory systems, providing inputs to many brain structures that regulate crucial visceral functions, including metabolism but also endocrine, cardiovascular, respiratory, and immune systems. Moreover, other visceral chemosensory systems monitor different essential chemical parameters of “milieu intérieur,” transmitting their data to the brain areas receiving taste and olfactory inputs; hence, they participate in regulating the same vital functions. These chemosensory cells share many molecular features with olfactory or taste receptor cells, thus they may be affected by the same pathological events. In most COVID-19 patients, taste and olfaction are disturbed. This may represent only a small portion of a broadly diffuse chemosensory incapacitation. Indeed, many COVID-19 peculiar symptoms may be explained by the impairment of visceral chemosensory systems, for example, silent hypoxia, diarrhea, and the “cytokine storm”. Dysregulation of chemosensory systems may underlie the much higher mortality rate of COVID-19 Acute Respiratory Distress Syndrome (ARDS) compared to ARDSs of different origins. In chronic non-infectious diseases like hypertension, diabetes, or cancer, the impairment of taste and/or olfaction has been consistently reported. This may signal diffuse chemosensory failure, possibly worsening the prognosis of these patients. Incapacitation of one or few chemosensory systems has negligible effects on survival under ordinary life conditions but, under stress, like metabolic imbalance or COVID-19 pneumonia, the impairment of multiple chemosensory systems may lead to dire consequences during the course of the disease.

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“…Similarly, chemosensory cells sensitive to internal signals are not narrowly tuned as previously alleged. For example, carotid body cells are sensitive to blood gases but also to glucose [ 11 ] and inflammatory mediators [ 12 , 13 ]; solitary chemoreceptor cells recognize microbial chemosignals [ 14 ] but also express sweet taste receptors that modulate the antimicrobial response [ 15 ]; pulmonary neuroendocrine cells can sense oxygen, carbon dioxide, and other different molecules, and are involved in ventilatory function and immunomodulation [ 16 , 17 , 18 ]; in the gastrointestinal tract, solitary chemoreceptor cells (aka tuft cells) recognize different microbial signals [ 19 ] while enterochromaffin cells also recognize glucose among other molecules [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

Are Multiple Chemosensory Systems Accountable for COVID-19 Outcome?

Caretta

Mucignat‐Caretta

2021

JCM

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Chemosensory systems (olfaction, taste, trigeminus nerve, solitary chemoreceptor cells, neuroendocrine pulmonary cells, and carotid body, etc.) detect molecules outside or inside our body and may share common molecular markers. In addition to the impairment of taste and olfaction, the detection of the internal chemical environment may also be incapacitated by COVID-19. If this is the case, different consequences can be expected. (1) In some patients, hypoxia does not trigger distressing dyspnea (“silent” hypoxia): Long-term follow-up may determine whether silent hypoxia is related to malfunctioning of carotid body chemoreceptors. Moreover, taste/olfaction and oxygen chemoreceptors may be hit simultaneously: Testing olfaction, taste, and oxygen chemoreceptor functions in the early stages of COVID-19 allows one to unravel their connections and trace the recovery path. (2) Solitary chemosensory cells are also involved in the regulation of the innate mucosal immune response: If these cells are affected in some COVID-19 patients, the mucosal innate immune response would be dysregulated, opening one up to massive infection, thus explaining why COVID-19 has lethal consequences in some patients. Similar to taste and olfaction, oxygen chemosensory function can be easily tested with a non-invasive procedure in humans, while functional tests for solitary chemosensory or pulmonary neuroendocrine cells are not available, and autoptic investigation is required to ascertain their involvement.

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Carotid Body and Metabolic Syndrome: Mechanisms and Potential Therapeutic Targets

Cited by 15 publications

References 218 publications

Immunity and the carotid body: implications for metabolic diseases

Immunity and the carotid body: implications for metabolic diseases

Not Only COVID-19: Involvement of Multiple Chemosensory Systems in Human Diseases

Are Multiple Chemosensory Systems Accountable for COVID-19 Outcome?

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