Mimecan, a Hormone Abundantly Expressed in Adipose Tissue, Reduced Food Intake Independently of Leptin Signaling

Chen, Hui; Ye, Xiaoping; Ma, Jiali; Jiang, He; Li, Shengxian; Li, Rong-Ying; Li, Xuesong; Guo, Cuicui; Wang, Zhiquan; Zhan, Ming; Zuo, Chao; Pan, Chun-Ming; Zhao, Shuang‐Xia; Zheng, Cuixia; Song, Huai‐Dong

doi:10.1016/j.ebiom.2015.09.044

Cited by 23 publications

(32 citation statements)

References 35 publications

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“…Similarly, we found mimecan protein on IR vesicles and also by immunoblot in EVs from hypertrophied cells paralleling its upregulation in vesicles isolated from human obese visceral adipose tissue [19]. This adipokine is abundantly expressed in AT and considered a satiety hormone that inhibits food intake independent of leptin signaling by inducing IL-1B and IL-6 expression in the hypothalamus [27]. Although it has not been described, we hypothesize that as occurs with leptin, this adipokine may be increasingly secreted during the development of obesity, and probably part of this secretion occurs through EVs as validated by immunoblot in the present research.…”

Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealmentioning

confidence: 73%

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Camino

Lago-Baameiro

Bravo

et al. 2020

IJMS

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Extracellular vesicles (EVs) have recently emerged as a relevant way of cell to cell communication, and its analysis has become an indirect approach to assess the cell/tissue of origin status. However, the knowledge about their nature and role on metabolic diseases is still very scarce. We have established an insulin resistant (IR) and two lipid (palmitic/oleic) hypertrophied adipocyte cell models to isolate EVs to perform a protein cargo qualitative and quantitative Sequential Window Acquisition of All Theoretical Mass Spectra (SWATH) analysis by mass spectrometry. Our results show a high proportion of obesity and IR-related proteins in pathological EVs; thus, we propose a panel of potential obese adipose tissue EV-biomarkers. Among those, lipid hypertrophied vesicles are characterized by ceruloplasmin, mimecan, and perilipin 1 adipokines, and those from the IR by the striking presence of the adiposity and IR related transforming growth factor-beta-induced protein ig-h3 (TFGBI). Interestingly, functional assays show that IR and hypertrophied adipocytes induce differentiation/hypertrophy and IR in healthy adipocytes through secreted EVs. Finally, we demonstrate that lipid atrophied adipocytes shed EVs promote macrophage inflammation by stimulating IL-6 and TNFα expression. Thus, we conclude that pathological adipocytes release vesicles containing representative protein cargo of the cell of origin that are able to induce metabolic alterations on healthy cells probably exacerbating the disease once established.

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Section: Despite the Recent Up Surge Of Extracellular Vesicles Revealmentioning

confidence: 73%

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Camino

Lago-Baameiro

Bravo

et al. 2020

IJMS

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“…A recent study in mice demonstrated that OGN functions as a satiety hormone in adipose tissue, where it is highly expressed and secreted into the circulation. Administration of OGN limits food intake in mice, possibly by increasing expression of IL‐1β and ‐6 in the hypothalamus, but independent of leptin signaling (86). Nevertheless, despite many studies implicating OGN in the metabolic syndrome, an actual role for OGN in the pathogenesis of the metabolic syndrome remains to be demonstrated.…”

Section: Ogn In Diseasementioning

confidence: 99%

The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease?

2016

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Small leucine-rich proteoglycans are emerging as important regulatory proteins within the extracellular matrix, where they exert both structural and nonstructural functions and hence are modulators of numerous biological processes, such as inflammation, fibrosis, and cell proliferation. One proteoglycan in particular, osteoglycin (OGN), also known as mimecan, shows great structural and functional diversity in normal physiology and in disease states, therefore making it a very interesting candidate for the development of novel therapeutic strategies. Unfortunately, the literature on OGN is confusing, as it has different names, and different transcript and protein variants have been identified. This review will give a clear overview of the different structures and functions of OGN that have been identified to date, portray its central role in pathophysiology, and highlight the importance of posttranslational processing, such as glycosylation, for the diversity of its functions.-Deckx, S., Heymans, S., Papageorgiou, A.-P. The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease? FASEB J. 30, 2651-2661 (2016). www.fasebj.orgThe extracellular matrix is a complex network of structural and nonstructural matrix proteins with a fundamental role in development, homeostasis, and pathophysiology. Small leucine-rich proteoglycans (SLRPs) are proteoglycans present in the extracellular matrix, where they are involved in a wide range of processes such as inflammation, fibrosis, and cell proliferation (1-4). Given the diversity of SLRPs, these proteoglycans are interesting targets for matrix-related research. In particular, osteoglycin (OGN), a class III SLRP member with multiple glycosylation sites, has been shown to be involved in many physiological processes (e.g., collagen fibrillogenesis, cell proliferation, and development), and in diverse pathologic entities, such as cardiovascular disease, cancer, and eye disease. Despite extensive research on OGN, the literature is rather confusing, because different names have been used for OGN, such as osteoinductive factor or mimecan, and different transcript and protein variants have been identified. Moreover, posttranslational processing, such as glycosylation, paramount in providing diversity in structure and function, is often poorly described. Hence, an identified function of OGN is rarely annotated to a certain transcript or glycosylated protein variant, adding to the confusion. Therefore, the purpose of this review is to give a clear overview of the different structures and functions of OGN known so far, highlight the importance of its glycosylation for the diversity in function, and describe its central role during normal physiology and in different pathological conditions. OGN: A DECEITFUL DWARFSLRPs have leucine-rich repeats (LRRs) (5), which are conserved motifs that are present from bacteria to humans and are critical for many processes, such as proteinprotein interactions, signal transduction, cell adhesion, and DNA repair (5). ...

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“…All cell cultures were routinely passaged at 90-95% con uency. Before the experiment, cells were preincubated with F-12K medium containing 0.2% BSA for24 h. Then treated with ACTH (sigma), DEX (sigma), MBP-mimecan fusion protein made in our lab (10), speci c cell pathway inhibitors, and so on. Medium samples were collected and stored at-80•C at the end of the experiments for hormone content analysis.…”

Section: Primary Adrenal Gland Cell Isolation and Cell Culturementioning

confidence: 99%

“…Mimecan-MBP fusion protein and MBP protein puri cation was conducted as described earlier by our group (10). The cDNA encoding 12 kDa human mimecan (residues 175-279) was subcloned into pGEX-5X-2 (GE Healthcare) and overexpressed in Escherichia coli BL21 (DE3) cells.…”

Section: Fusion Protein Puri Cation and Antibody Productionmentioning

confidence: 99%

“…To date, the physiologic functions of mimecan remain obscure. We have previously cloned the full-length cDNA of human mimecan (accession number: AF100758) (9), establishing mimecan as a novel satiety hormone in adipose tissue propagated by IL-1β and IL-6 induction within hypothalamus (10). Our previous studies have also shown that mimecan is expressed in human pituitary corticotroph cells and the AtT-20 mouse corticotroph cell line and mimecan gene expression in pituitary corticotroph cells is up-regulated by glucocorticoid (GC) in a time-and dose-dependent manner (9,11).…”

Section: Introductionmentioning

confidence: 99%

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Mimecan Regulates Corticosterone Secretion and Plays A Critical Role in Adrenal Responses to Stress

Su¹,

Zhang²,

Li³

et al. 2020

Preprint

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Background: A functional hypothalamic-pituitary-adrenal (HPA) axis is critical for host defenses to outside stimuli. The adrenal cortex is seemingly endowed with distinct functional units that are regulated by adrenocorticotropic hormone (ACTH). We have found that mimecan, a small leucine-rich proteoglycan expressed in the adrenal gland, has yet to be characterized in functional terms.Results: Herein, we have demonstrated the following properties: 1) adrenal mimecan expression in mouse models is significantly downregulated under hypoglycemia and scalded stress; 2) expression of mimecan in adrenal cells may be downregulated through ACTH or upregulated by glucocorticoid via related receptors (GRs); and 3) mimecan stimulates corticosterone secretion in adrenal tissues. The latter was proven using in vivo and in vitro studies to confirm the ACTH-independent activity of mimecan-maltose-binding protein (-MBP). Relative to litter-mate mice, the basal-state diurnal rhythm of corticosterone secretion is disrupted in mimecan knockout mice, and corticosterone secretion is increased under restraint stress conditions. Conclusions: These findings offer the first evidence that mimecan is key in regulating the HPA axis, assuming a critical role in adrenal responses to stress.

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Mimecan, a Hormone Abundantly Expressed in Adipose Tissue, Reduced Food Intake Independently of Leptin Signaling

Cited by 23 publications

References 35 publications

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

Vesicles Shed by Pathological Murine Adipocytes Spread Pathology: Characterization and Functional Role of Insulin Resistant/Hypertrophied Adiposomes

The diverse functions of osteoglycin: a deceitful dwarf, or a master regulator of disease?

Mimecan Regulates Corticosterone Secretion and Plays A Critical Role in Adrenal Responses to Stress

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