Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance

Meex, Ruth C. R.; Watt, Matthew J.

doi:10.1038/nrendo.2017.56

Cited by 495 publications

(455 citation statements)

References 189 publications

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“…These diseases that are associated with NAFLD may increase the risk of cardiovascular disease and further aggravate the liver damage [68]. Therefore, the key to the treatment of NAFLD is the improvement of the metabolic disturbances associated with insulin resistance [69]. Insulin-sensitizing drugs, such as metformin, may correct some of these metabolic disorders [70].…”

Section: Discussionmentioning

confidence: 99%

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

Guo

Zhou

Cheng

et al. 2018

Cell Physiol Biochem

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Background/Aims: Recent studies have suggested that changes in non-coding mRNA play a key role in the progression of non-alcoholic fatty liver disease (NAFLD). Metformin is now recommended and effective for the treatment of NAFLD. We hope the current analyses of the non-coding mRNA transcriptome will provide a better presentation of the potential roles of mRNAs and long non-coding RNAs (lncRNAs) that underlie NAFLD and metformin intervention. Methods: The present study mainly analysed changes in the coding transcriptome and non-coding RNAs after the application of a five-week metformin intervention. Liver samples from three groups of mice were harvested for transcriptome profiling, which covered mRNA, lncRNA, microRNA (miRNA) and circular RNA (circRNA), using a microarray technique. Results: A systematic alleviation of high-fat diet (HFD)-induced transcriptome alterations by metformin was observed. The metformin treatment largely reversed the correlations with diabetes-related pathways. Our analysis also suggested interaction networks between differentially expressed lncRNAs and known hepatic disease genes and interactions between circRNA and their disease-related miRNA partners. Eight HFD-responsive lncRNAs and three metformin-responsive lncRNAs were noted due to their widespread associations with disease genes. Moreover, seven miRNAs that interacted with multiple differentially expressed circRNAs were highlighted because they were likely to be associated with metabolic or liver diseases. Conclusions: The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD.

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Section: Discussionmentioning

confidence: 99%

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

Guo

Zhou

Cheng

et al. 2018

Cell Physiol Biochem

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“…Furthermore, the liver participates in metabolic regulation, through the expression and secretion of organokines, which are also referred to as hepatokines. Interestingly, these proteins influence metabolic processes through paracrine and endocrine signaling, rather than by autocrine signaling (17). Hepatokines include several growth factors such as fibroblast growth factor 21 (18), insulin-like growth factors, angiopoietin-related growth factor, and HGF.…”

Section: Introductionmentioning

confidence: 99%

The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes

et al. 2018

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In obesity, insulin resistance (IR) and diabetes, there are proteins and hormones that may lead to the discovery of promising biomarkers and treatments for these metabolic disorders. For example, these molecules may impair the insulin signaling pathway or provide protection against IR. Thus, identifying proteins that are upregulated in IR states is relevant to the diagnosis and treatment of the associated disorders. It is becoming clear that hepatocyte growth factor (HGF) is an important component of the pathophysiology of IR, with increased levels in most common IR conditions, including obesity. HGF has a role in the metabolic flux of glucose in different insulin sensitive cell types; plays a key role in β-cell homeostasis; and is capable of modulating the inflammatory response. In this review, we discuss how, and to what extent HGF contributes to IR and diabetes pathophysiology, as well as its role in cancer which is more prevalent in obesity and diabetes. Based on the current literature and knowledge, it is clear that HGF plays a central role in these metabolic disorders. Thus, HGF levels could be employed as a biomarker for disease status/progression, and HGF/c-Met signaling pathway modulators could effectively regulate IR and treat diabetes.

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“…Accumulating evidence has suggested that hepatokines, such as Fetuin-A, retinol-binding protein 4, sex hormone-binding globulin and adropin, play as important roles in the link of NAFLD to insulin resistance [36]. Fetuin-B, as one of the novel hepatokines that induced metabolic dysregulation, was also found to be associated with insulin resistance.…”

Section: Discussionmentioning

confidence: 95%

Fetuin-B Links Nonalcoholic Fatty Liver Disease to Chronic Kidney Disease in Obese Chinese Adults: A Cross-Sectional Study

Lin

Liu

et al. 2019

Ann Nutr Metab

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Background: There is no evidence available on the association of Fetuin-B with chronic kidney disease (CKD), and mechanisms linking nonalcoholic fatty liver disease (NAFLD) to CKD are not fully understood. We aimed to explore the independent associations and potential mechanisms of Fetuin-B and NAFLD with CKD. Methods: A cross-sectional study of 1,072 Chinese adults who underwent serum Fetuin-B test and hepatic ultrasonography scanning was conducted in Xiamen, China. CKD was defined as estimated glomerular filtration rate < 60 mL/min/1.73 m² and/or the presence of albuminuria. Results: Subjects with CKD showed significantly higher prevalence of NAFLD (69.5 vs. 57.2%, p < 0.001) and serum Fetuin-B levels (4.32 ± 1.45 vs. 4.05 ± 1.36 µg/mL, p = 0.007) than their controls. Increased serum Fetuin-B was also significantly associated with increased levels of fasting insulin and homeostasis model assessment – insulin resistance (both p values < 0.05). NAFLD and higher serum Fetuin-B were significantly associated with increased risk of CKD, and the unadjusted ORs (95% CIs) were 1.701 (1.256–2.303, p = 0.001) and 1.213 (1.053–1.399, p = 0.008, per SD increase of Fetuin-B), respectively. With adjustment for potential confounding factors, including metabolic/insulin resistance syndrome, NAFLD but not serum Fetuin-B was still significantly associated with increased risk of CKD, and the adjusted ORs (95% CIs) were 1.820 (1.327–2.496, p < 0.001) and 1.116 (0.959–1.298, p = 0.153, per SD increase of Fetuin-B), respectively. Conclusions: Fetuin-B might link NAFLD to CKD via inducing insulin resistance, and NAFLD contributes independently to the pathogenesis of CKD via multiple mechanisms besides of metabolic/insulin resistance syndrome.

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Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance

Cited by 495 publications

References 189 publications

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice

The Role of Hepatocyte Growth Factor (HGF) in Insulin Resistance and Diabetes

Fetuin-B Links Nonalcoholic Fatty Liver Disease to Chronic Kidney Disease in Obese Chinese Adults: A Cross-Sectional Study

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