OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin

Li, Erwei; Shan, Haili; Chen, Liqun; Long, A. G.; Zhang, Yuanyuan; Liu, Yang; Jia, Liangjie; Wei, Fangchao; Han, Jin; Li, Tong; Liu, Xiaohui; Deng, Haiteng; Wang, Yiguo

doi:10.1016/j.cmet.2019.05.022

Cited by 138 publications

(127 citation statements)

References 48 publications

(54 reference statements)

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“…First, Li et al confirmed the gluconeogenic effect of asprosin and discovered one of the receptors responsible for it by utilizing more soluble GSTasprosin. Of note, they noted that the activity of recombinant asprosin depended heavily on its quality, and it was hard to purify His-asprosin from E. coli, which is consistent with the findings from Li et al (11) and von Herrath et al (12). Second, Chopra's team published another study and confirmed that a single dose of asprosin injected subcutaneously, either bacterially derived or mammalian-expressed, did cross the bloodbrain barrier and promote food intake in mice (6).…”

Section: Introductionsupporting

confidence: 82%

“…on G protein-coupled receptor (GPCR), which activates the adenylyl cyclase-PKA-cAMP responsive element binding (CREB) pathway and leads to the production and release of glucose (1). Recently, olfactory receptor 734 (OLFR734) has been determined to be one of the receptors of asprosin to mediate this effect; nevertheless, it is not the sole receptor responsible for asprosin glucogenic function (11). By binding with the unknown receptors expressed at mouse skeletal muscle cells, asprosin impairs insulin sensitivity via activating PKCδ/SERCA2-mediated endoplasmic reticulum (ER) stress/inflammation pathways.…”

Section: Introductionmentioning

confidence: 99%

“…What should be worth noticing is that the effects of asprosin on glucogenesis and appetite remain controversial (1,6,8,11,12). A pre-clinical replication study by von Herrath et al failed to confirm the glucogenic and orexigenic effects of asprosin reported by the group of Chopra.…”

Section: Introductionmentioning

confidence: 99%

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Asprosin: A Novel Player in Metabolic Diseases

Yuan

Zhu

et al. 2020

Front. Endocrinol.

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Asprosin, a novel glucogenic adipokine, is encoded by two exons (exon 65 and exon 66) of the gene Fibrillin 1 (FBN1) and mainly synthesized and released by white adipose tissue during fasting. Asprosin plays a complex role in the central nervous system (CNS), peripheral tissues, and organs. It is involved in appetite, glucose metabolism, insulin resistance (IR), cell apoptosis, etc. In this review, we will summarize the newly discovered roles of asprosin in metabolic diseases including diabetes, obesity, polycystic ovarian syndrome (PCOS), and cardiovascular disease (CVD), which may contribute to future clinical diagnosis and treatment.

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Section: Introductionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

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Asprosin: A Novel Player in Metabolic Diseases

Yuan

Zhu

et al. 2020

Front. Endocrinol.

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“…Surprisingly, among the four most ubiquitous enriched pathways for ACE2 and/or TMPRSS2-correlated genes, we found olfactory and taste transduction. Both OR and TAS genes occur in "ectopic" locations within and outside the brain, and could play roles other than odor or taste perception, such as the sensing of peripheral metabolites by hypothalamic tanycytes (53)(54)(55) or the mediation of viral infection or the host response (56,57), and could be over-or under-expressed in disorders like obesity or diabetes (58).…”

Section: Discussionmentioning

confidence: 99%

The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

Nampoothiri

Sauvé

Ternier

et al. 2020

Preprint

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Most patients with COVID-19, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), display neurological symptoms, and respiratory failure in certain cases could be of extrapulmonary origin. Hypothalamic neural circuits play key roles in sex differences, diabetes, hypertension, obesity and aging, all risk factors for severe COVID-19, besides being connected to olfactory/gustative and brainstem cardiorespiratory centers. Here, human brain gene-expression analyses and immunohistochemistry reveal that the hypothalamus and associated regions express angiotensin-converting enzyme 2 and transmembrane proteinase, serine 2, which mediate SARS-CoV-2 cellular entry, in correlation with genes or pathways involved in physiological functions or viral pathogenesis. A post-mortem patient brain shows viral invasion and replication in both the olfactory bulb and the hypothalamus, while animal studies indicate that sex hormones and metabolic diseases influence this susceptibility. Main textSARS-CoV-2 infection is increasingly associated with a wide range of neurological symptomsheadaches, dizziness, nausea, loss of consciousness, seizures, encephalitis etc., as well as anosmia or ageusia -in the majority of patients (1,2). Additionally, many COVID-19 patients with severe disease do not respond well to artificial ventilation or display "silent hypoxia" (3), suggesting an extrapulmonary component to respiratory dysfunction, and cardiorespiratory function and fluid homeostasis are themselves subject to central nervous system (CNS) control. However, despite emerging reports of the post-mortem detection of the virus in the cerebrospinal fluid (CSF) (see for example (4)) or brain parenchyma of patients (5), little is known about how and under what circumstances SARS-CoV-2 infects the brain.While the possibility of CNS infection has been largely underestimated due to the common view that angiotensin converting enzyme 2 (ACE2), the only confirmed cellular receptor for SARS-CoV-2 so far (6), is absent or expressed only at very low levels in the brain (7,8), and that too exclusively in vascular cells (He et al., bioRxiv 2020; doi: https://doi.org/10.1101.088500) the majority of these studies have focused on the cerebral cortex, ignoring the fact that other regions such as the hypothalamus, are rich in ACE2 (9). Intriguingly, most major risk factors for severe COVID-19 (male sex, age, obesity, hypertension, diabetes); reviewed by (10,11); could be mediated by normal or dysfunctional hypothalamic neural networks that regulate a variety of physiological processes: sexual differentiation and gonadal hormone production, energy homeostasis, fluid homeostasis/osmoregulation and even ageing (12)(13)(14). The hypothalamus is also directly linked to other parts of the CNS involved in functions affected in COVID-19 patients, including brainstem nuclei that control fluid homeostasis, cardiac function and respiration, as well as regions implicated in the perception or integration of odor and taste (12,(14)(15)(16)(17)(18).Here, we inves...

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“…We think that detecting higher levels of asprosin in obese individuals during childhood is more critical than adults. In a recent study, it was shown that OLFR734 as a receptor of asprosin could maintain glucose homeostasis during fasting and in obesity . It is possible to create an external agent to regulate asprosin receptors; therefore, it may also be possible to regulate glucose, appetite, and obesity with this agent in the future.…”

Section: Discussionmentioning

confidence: 99%

Increased serum circulating asprosin levels in children with obesity

Silistre¹,

Hatipoğl²

2020

Pediatrics International

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Background: Childhood obesity is a growing and significant problem worldwide. Asprosin is a novel adipokine that is significantly associated with glucose and insulin production in the liver during fasting. In the present study, we aimed to demonstrate whether there would be differences between obese, overweight, and normal weight children in terms of serum asprosin levels. Methods: Forty-four children with obesity, 54 overweight children, and 60 normal weight children were compared in terms of serum asprosin levels and other anthropometric, biochemical, and hormonal parameters that are associated with being overweight and with obesity. Results: Serum asprosin levels were found to be significantly different between groups: 70.903 AE 17.49 ng/mL, 79.744 AE 29.54 ng/mL, and 106.293 AE 122.69 ng/mL in normal weight, overweight, and obese children respectively. Post-hoc analysis revealed that the asprosin level was significantly higher in obese children compared with normal weight children (P = 0.009). Additionally, asprosin was found to be a predictor of obesity in multiple regression analysis. Conclusion: Our study is the first to demonstrate increased levels of asprosin in obese children compared with normal weight children. Further studies are needed to demonstrate the role of asprosin in the etiology of childhood obesity, as well as other diseases that might be associated with effects of asprosin.

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OLFR734 Mediates Glucose Metabolism as a Receptor of Asprosin

Abstract: Highlights d Olfr734 deficiency decreases gluconeogenesis and increases insulin sensitivity d OLFR734 is a receptor of Asprosin d Asprosin promotes hepatic glucose production via OLFR734 d Asprosin-OLFR734 maintains glucose homeostasis during fasting and in obesity

Cited by 138 publications

References 48 publications

Asprosin: A Novel Player in Metabolic Diseases

Asprosin: A Novel Player in Metabolic Diseases

The hypothalamus as a hub for SARS-CoV-2 brain infection and pathogenesis

Increased serum circulating asprosin levels in children with obesity

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