Increased plasma osteopontin levels are associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

He, Miao; Peng, Jiajia; Li, Shengbing; Long, Min; Chen, Wenwen; Liu, Dongfang; Yang, Gangyi; Zhang, Lili

doi:10.1016/j.cyto.2019.154837

Cited by 15 publications

(13 citation statements)

References 35 publications

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“…Third, a serological marker for DM-related liver diseases akin to the use of urine albumin excretion to screen for diabetic nephropathy should be investigated. A recent study has shown, for example, that the circulating level of osteopontin (OPN), a soluble pluripotent glycophosphoprotein and a proinflammatory cytokine, may be useful in diagnosing NAFLD in patients with DM[ 240 ]. Fourth, given the impact of DM on the progressive of CLD and liver disease complications, it would be interesting to see if the inclusion of a glycemic marker in the calculation of the MELD score would improve its predictive value for the short-term survival and liver disease severity.…”

Section: Future Directionsmentioning

confidence: 99%

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

Chung

Promrat

Wands

2020

WJH

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Diabetes mellitus (DM) negatively affects the development and progression of chronic liver diseases (CLD) of various etiologies. Concurrent DM and CLD are also associated with worse clinical outcomes with respect to mortality, the occurrence of hepatic decompensation, and the development of hepatocellular carcinoma (HCC). Unfortunately, early diagnosis and optimal treatment of DM can be challenging, due to the lack of established clinical guidelines as well as the medical complexity of this patient population. We conducted an exploratory review of relevant literature to provide an up-to-date review for internists and hepatologists caring for this patient population. We reviewed the epidemiological and pathophysiological associations between DM and CLD, the impact of insulin resistance on the progression and manifestations of CLD, the pathogenesis of hepatogenic diabetes, as well as the practical challenges in diagnosis and monitoring of DM in this patient population. We also reviewed the latest clinical evidence on various pharmacological antihyperglycemic therapies with an emphasis on liver disease-related clinical outcomes. Finally, we proposed an algorithm for managing DM in patients with CLD and discussed the clinical and research questions that remain to be addressed.

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Section: Future Directionsmentioning

confidence: 99%

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

Chung

Promrat

Wands

2020

WJH

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“…SPP1 is seldomly expressed in normal liver tissue and is mainly expressed in activated Kupffer cells, hepatic macrophages, hepatic stellate cells, and hepatocytes under pathological conditions ( 17 – 19 ). As a multifunctional protein, SPP1 is involved in multiple liver diseases by promoting inflammatory responses, cell activation, proliferation, and migration, and is closely related to the occurrence, development, and prognosis of fatty liver, liver fibrosis, and liver cancer ( 20 , 21 ). Previous studies have revealed that the expression of SPP1 is upregulated in NAFLD and NASH liver tissues.…”

Section: Discussionmentioning

confidence: 99%

SPP1 and CXCL9 Promote Non-alcoholic Steatohepatitis Progression Based on Bioinformatics Analysis and Experimental Studies

et al. 2022

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Background and AimsNon-alcoholic fatty liver disease (NAFLD) is a major chronic liver disease worldwide, and non-alcoholic steatohepatitis (NASH) is one of its pathological subtypes. The pathogenesis of NASH has not yet been fully elucidated. The purpose of this study was to identify the hub genes and pathways involved in NASH using bioinformatics methods. The hub genes were confirmed in human and animal models.Materials and MethodsThree Gene Expression Omnibus (GEO) datasets (GSE48452, GSE58979, and GSE151158) of NASH patients and healthy controls were included in the study. We used GEO2R to identify differentially expressed genes (DEGs) between NASH patients and healthy controls. Functional enrichment analyses were then performed to explore the potential functions and pathways of the DEGs. In all DEGs, only two genes were highly expressed in NASH patients throughout the three datasets; these two genes, SPP1 and CXCL9, were further studied. Serum and liver tissues from NASH patients and healthy controls were collected. Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were measured in NASH patients and healthy controls. Liver tissues were stained with hematoxylin and eosin. Immunohistochemical staining was used to evaluate the expression levels of the two genes in liver tissues. Male C57BL/6J mice were fed a methionine choline-deficient (MCD) diet for 8 weeks, after which serum ALT and AST levels were measured and liver tissues were stained.ResultsSPP1 and CXCL9 were the hub genes detected in the three datasets. “Lipid metabolism,” “inflammatory response,” and “lymphocyte activation” were the most significant biological functions in GSE48452, GSE58979, and GSE151158, respectively. Kyoto Encyclopedia of Genes and Genomes pathway analysis showed that the toll-like receptor signaling pathway was significantly enriched in NASH patients. Serum ALT and AST levels were significantly increased in NASH patients compared to healthy controls. Liver tissues had more serious steatosis, hepatocyte ballooning degeneration, and lobular inflammatory infiltration, and the expression of SPP1 and CXCL9 in liver cells was significantly upregulated in NASH patients compared to healthy controls. MCD diet mice were consistent with NASH patients.ConclusionSPP1 and CXCL9 may play important roles in NASH pathogenesis and could be potential therapeutic targets and biomarkers of NASH in the future. Further experimental studies are needed to confirm our results.

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“…Whereas the association between OPN and diabetes has been long time recognized at epidemiological level, 29,30 the underlying mechanisms are increasingly uncovered. A direct effect of OPN on hepatocytes would target insulin receptor substrate‐2 (IRS‐2) and gluconeogenic genes (ie phosphoenolpyruvate carboxykinase and glucose 6 phosphatase), thus representing a connection ring between hepatic steatosis and insulin resistance 31,32 . In turn, hyperglycaemia may stimulate OPN synthesis and release through inflammatory mechanisms on endothelial cells, vascular smooth muscle cells and macrophages 33‐35 .…”

Section: Discussionmentioning

confidence: 99%

Serum osteopontin predicts glycaemic profile improvement in metabolic syndrome: A pilot study

Caserza

Casula

Elia

et al. 2020

Eur J Clin Investigation

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Prediabetes is often observed in patients with Metabolic Syndrome (MetS) and might be associated with metabolic and inflammatory alterations. Here, we investigated whether the inflammatory molecule osteopontin (OPN) might have a prognostic impact in a cohort of MetS patients (n = 85) with baseline normal glycaemia or impaired fasting glucose (IFG) over one year of recommended pharmacological treatments and Mediterranean diet. Patients were then followed up for 12 months with intermediate evaluation after 6 months. At all time points, anthropometric and clinical data were recorded, alongside with haematological and biochemical profiles, including serum concentrations of OPN. As expected, Mediterranean diet improves glycaemic profile in patients with IFG. Baseline serum OPN failed to be associated with baseline anthropometric or biochemical variables. At baseline, higher levels of OPN were shown in patients with IFG as compared to normal glycaemia. Two distinct subgroups of patients in whom OPN decreased or remained stable/increased at follow‐up were identified. When higher serum OPN levels were observed at baseline, greater reduction was observed at 1‐year follow‐up. Reduction in circulating OPN levels was associated with metabolic improvement in terms of blood pressure, LDL‐c, HDL‐c, and glycaemia. At both univariate and adjusted logistic regression analyses, serum OPN emerged as an independent predictor of glycaemic profile improvement at 1‐year follow‐up (adjOR 1.05 [1.00‐1.10]; P = .041). In conclusion, pharmacological and dietetic interventions improved glycaemic profile in patients with MetS. In particular, glycaemic improvement was demonstrated in patients who also reduce circulating OPN levels. Higher OPN levels at baseline predict normalization of glycaemic profile.

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Increased plasma osteopontin levels are associated with nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Cited by 15 publications

References 35 publications

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

Clinical implications, diagnosis, and management of diabetes in patients with chronic liver diseases

SPP1 and CXCL9 Promote Non-alcoholic Steatohepatitis Progression Based on Bioinformatics Analysis and Experimental Studies

Serum osteopontin predicts glycaemic profile improvement in metabolic syndrome: A pilot study

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