Protein tyrosine phosphatase receptor δ serves as the orexigenic asprosin receptor

Mishra, Ila; Xie, Wei; Bournat, Juan C.; He, Yang; Wang, Chunmei; Silva, Elizabeth Sabath; Liu, Hailan; Ku, Zhiqiang; Chen, Yinghua; Erokwu, Bernadette O.; Jia, Peilin; Zhao, Zhongming; An, Zhiqiang; Flask, Chris A.; He, Yanlin; Xu, Yong; Chopra, Atul R.

doi:10.1016/j.cmet.2022.02.012

Cited by 26 publications

(43 citation statements)

References 53 publications

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“…Nutritional complementarity is primary to an organism’s growth and development via regulation of multiple cytokines (leptin, adiponectin, asprosin, acyl-CoA-binding protein and so on) and growth factors and hormones (insulin/IGF-1, FGF21, thyroid-stimulating hormone, prolactin, corticosterone, etc.). 80 , 152 – 156 Insulin and IGF-1 were first discovered to be connected to diet and health. The orthologue of the mammalian insulin/IGF-1 receptor in C. elegans is encoded by the daf-2 gene, and its mutation has been found to dramatically prolong longevity.…”

Section: Nutrient-associated Molecular Mechanismsmentioning

confidence: 99%

Dietary regulation in health and disease

Gao

et al. 2022

Sig Transduct Target Ther

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Nutriments have been deemed to impact all physiopathologic processes. Recent evidences in molecular medicine and clinical trials have demonstrated that adequate nutrition treatments are the golden criterion for extending healthspan and delaying ageing in various species such as yeast, drosophila, rodent, primate and human. It emerges to develop the precision-nutrition therapeutics to slow age-related biological processes and treat diverse diseases. However, the nutritive advantages frequently diversify among individuals as well as organs and tissues, which brings challenges in this field. In this review, we summarize the different forms of dietary interventions extensively prescribed for healthspan improvement and disease treatment in pre-clinical or clinical. We discuss the nutrient-mediated mechanisms including metabolic regulators, nutritive metabolism pathways, epigenetic mechanisms and circadian clocks. Comparably, we describe diet-responsive effectors by which dietary interventions influence the endocrinic, immunological, microbial and neural states responsible for improving health and preventing multiple diseases in humans. Furthermore, we expatiate diverse patterns of dietotheroapies, including different fasting, calorie-restricted diet, ketogenic diet, high-fibre diet, plants-based diet, protein restriction diet or diet with specific reduction in amino acids or microelements, potentially affecting the health and morbid states. Altogether, we emphasize the profound nutritional therapy, and highlight the crosstalk among explored mechanisms and critical factors to develop individualized therapeutic approaches and predictors.

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Section: Nutrient-associated Molecular Mechanismsmentioning

confidence: 99%

Dietary regulation in health and disease

Gao

et al. 2022

Sig Transduct Target Ther

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“…Molecular functions dysregulated by asprosin are presented in Figure 3 C,D, and include hormone binding, cell adhesion as well as protein tyrosine phosphatase activity; a process recently associated with asprosin mediated appetite stimulation [ 54 ]. Additional processes detected indicate that asprosin related DEGs are connected to the regulation of insulin as well as glucose, which align with asprosin’s metabolic profile as a glucogenic hormone capable of influencing homeostasis, its role following OR4M1 binding, as well as asprosin’s role in insulin resistance [ 6 ].…”

Section: Discussionmentioning

confidence: 99%

“…Asprosin appears through the literature to bind promiscuously to three diverse receptors, each responsible for a distinct biological response. Indeed, binding to Olfactory Receptor 4 Member 1 (OR4M1), a G-protein coupled receptor (GPCR), implicates asprosin with glucose regulation; binding to Toll Like Receptor 4 (TLR4), which is aberrantly expressed in OvCa tissues of varying stages, grades and subtypes ( Supplementary Figure S2 ), associates asprosin with insulin resistance in skeletal muscle [ 2 , 72 ]; emerging evidence also implicates stimulation of Protein Tyrosine Phosphatase Receptor delta (PTPRd) by asprosin as a mediator of orexigenic influence [ 54 ]. Additional work should seek the use of cross-linked proteins with immunoprecipitation and mass spectrometry to identify which, if not all, receptors asprosin binds to in a cell- or organ-specific manner.…”

Section: Discussionmentioning

confidence: 99%

Differential Regulation of Genes by the Glucogenic Hormone Asprosin in Ovarian Cancer

Kerslake

Sisu

Panfilov

et al. 2022

JCM

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Background: Ovarian cancer (OvCa) is one of the most lethal forms of gynaecological malignancy. Altered energy metabolism and increased aerobic glycolysis in OvCa are hallmarks that demand attention. The glucogenic hormone asprosin is often dysregulated in metabolic disorders such as insulin resistance, diabetes (type 2 and gestational), and preeclampsia. Despite association with metabolic disorders, its role in energy metabolism within the tumour microenvironment is yet to be explored. Here, we study the role of asprosin in OvCa using transcriptomics and expand on functional studies with clinical samples. Methods: RNA sequencing, functional gene enrichment analysis, Western blotting and ImageStream. Results: Following treatment with 100 nM of asprosin, the serous OvCa cell line, SKOV-3, displayed 160 and 173 gene regulatory changes, at 4 and 12 h respectively, when compared with control samples (p < 0.05 and Log2FC > 1). In addition to energy metabolism and glucose-related pathways, asprosin was shown to alter pathways associated with cell communication, TGF-β signalling, and cell proliferation. Moreover, asprosin was shown to induce phosphorylation of ERK1/2 in the same in vitro model. Using liquid biopsies, we also report for novel expression of asprosin’s predicted receptors OR4M1 and TLR4 in cancer-associated circulating cells; with significant reduction seen between pre-chemotherapy and end of first line chemotherapy, in addition to patients under maintenance with bevacizumab +/− olaparib for OR4M1. Conclusions: In relation to OvCa, asprosin appears to regulate numerous signalling pathways in-vitro. The prognostic potential of OR4M1 in liquid biopsies should also be explored further.

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“… Note: Mice injected with AAV8-empty (1 × 10 12 GC/mouse) will serve as control for experimental mice injected with AAV8-IL2sp-6His-Asprosin (1 × 10 12 GC/mouse). AAV8 dilutions should be prepared as suggested in the section 4 of the protocol ( Mishra et al., 2021 , 2022 ). Ad5-h FBN1 (150 μL, 3.6 × 10 9 pfu/mouse) can also be used for asprosin overexpression in mice.…”

Section: Step-by-step Methods Detailsmentioning

confidence: 99%