Decreased plasma neuregulin 4 concentration is associated with increased high-sensitivity C-reactive protein in newly diagnosed type 2 diabetes mellitus patients: a cross-sectional study

Yan, Pingping; Xu, Yong; Wan, Qin; Feng, Jian; Li, Hua; Gao, Chenlin; Yang, Jun; Zhong, Haihua; Zhang, Zhihong

doi:10.1007/s00592-017-1044-4

Cited by 24 publications

(17 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, a clinical study showed that decreased plasma concentrations of Nrg4 might be linked to increased levels of hs‐CRP in patients with T2DM. Moreover, hs‐CRP was the factor most severely related to circulating Nrg4 levels . Therefore, a significant negative association between plasma Nrg4 levels and hs‐CRP may lead to new insights into the anti‐inflammatory actions of Nrg4 in the development of DPN in T2DM.…”

Section: Discussionmentioning

confidence: 98%

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

et al. 2019

View full text Add to dashboard Cite

Neuregulin 4 (Nrg4), a novel brown fat-enriched hormone, plays a key role in the modulation of glucose and lipid metabolism and energy balance. Recent data have demonstrated that the expression of Nrg4 is substantially down-regulated in mouse and human obesity, making its regulatory aspect intriguing. Because of the close relationship between Nrg4, obesity, and associated metabolic diseases, this systematic review aimed to assess the association of Nrg4 with obesity and related metabolic disturbances, emphasizing its possible mechanisms of action in these disorders. We searched PubMed/Medline, ScienceDirect, Scopus, EMBASE, ProQuest, and Google Scholar up until June 2019. The evidence reviewed here indicates that Nrg4 may contribute to the prevention of obesity and related metabolic complications by elevating brown adipose tissue activity, increasing the expression of thermogenic markers, decreasing the expression of lipogenic/ adipogenic genes, exacerbating white adipose tissue browning, increasing the number of brite/beige adipocytes, promoting hepatic fat oxidation and ketogenesis, inducing neurite outgrowth, enhancing blood vessels in adipose tissue, increasing the circulatory levels of healthy adipokines, and improving glucose homeostasis.Thus, Nrg4 appears to be a novel therapeutic strategy for the treatment of obesity and associated metabolic complications. However, prospective cohort studies are warranted to confirm these outcomes.

show abstract

Section: Discussionmentioning

confidence: 98%

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

et al. 2019

View full text Add to dashboard Cite

show abstract

“…Although NRG1 can bind to both ErbB3 and ErbB4, activation of ErbB4 was proven to be critical for the increased glucose uptake, as ErbB4-blocking antibodies impaired NRG1-induced glucose uptake (3). NRG4, a ligand that specifically binds to ErbB4, has been reported to promote "browning" of white fat, fuel oxidation, prevention of high-fat diet-induced obesity, and improvement of insulin sensitivity (6,15,29). These findings suggest that ErbB4 may play an important role in metabolic regulation.…”

Section: Introductionmentioning

confidence: 99%

ErbB4 deletion predisposes to development of metabolic syndrome in mice

Zeng

Wang

Kloepfer

et al. 2018

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

ErbB4, a member of the EGF receptor family, plays a variety of roles in physiological and pathological states. Genetic studies have indicated a link between ErbB4 and type 2 diabetes and obesity, but its role in metabolic syndrome (MetS) has not been reported. In the current study we found that mice with ErbB4 deletion developed MetS after 24 wk on a medium-fat diet (MFD), as indicated by development of obesity, dyslipidemia, hepatic steatosis, hyperglycemia, hyperinsulinemia, and insulin resistance, compared with wild-type mice. ErbB4 deletion mice also exhibited increased amounts of subcutaneous and visceral fat, with increased serum leptin levels, compared with wild-type mice, whereas levels of adiponectin were not significantly different. Histologically, severe inflammation, indicated by F4/80 immunostaining and M1 macrophage polarization, was detected in inguinal and epididymal white adipose tissue in ErbB4 deletion mice. ErbB4 expression decreased during 3T3-L1 preadipocyte differentiation. Administration of neuroregulin 4, a specific ligand for ErbB4, to 3T3-L1 adipocytes had no effect on adipogenesis and lipolysis but significantly inhibited lipogenesis, promoted browning, induced GLUT4 redistribution to the cell membrane, and increased glucose uptake. Neuroregulin 4 also significantly increased glucose uptake in adipocytes isolated from wild-type mice, while these effects were significantly decreased in adipocytes isolated from ErbB4 deletion mice. In conclusion, our results indicate that ErbB4 may play an important role in glucose homeostasis and lipogenesis. ErbB4 deficiency-related obesity and adipose tissue inflammation may contribute to the development of MetS.

show abstract

“…However, other findings indicate that circulating Nrg4 concentrations may be a protective factor in the development of metabolic syndrome. For instance, in newly diagnosed patients with type 2 diabetes, lower plasma Nrg4 levels were associated with elevated high-sensitivity C-reactive protein (26). In obese adults, subjects with low levels of circulating Nrg4 had high prevalence of fasting glucose and blood pressure (27).…”

Section: Discussionmentioning

confidence: 99%

Elevated serum neuregulin 4 levels in patients with hyperthyroidism

Chen

Jiang

et al. 2019

Endocrine Connections

View full text Add to dashboard Cite

Objective Recent studies have shown that neuregulin 4 (Nrg4), a member of the epidermal growth factor (EGF) family of extracellular ligands, plays an important role in the prevention of obesity, insulin resistance and nonalcoholic fatty liver disease (NAFLD). Considering that thyroid hormone (TH) has profound effects on whole-body energy metabolism, we speculate that circulating Nrg4 levels might be altered in patients with hyperthyroidism. Design and methods A total of 129 hyperthyroid patients and 100 healthy subjects were recruited. Of them, 39 hyperthyroid patients received thionamide treatment for 3 months until euthyroidism. Serum Nrg4 levels were determined using the ELISA method. To further confirm the relationship between TH and Nrg4, C57BL/6 mice were treated with T3 and quantitative real-time PCR was performed to detect Nrg4 gene expression. Results Serum Nrg4 levels were significantly elevated in hyperthyroid patients as compared with normal controls (3.84 ± 1.63 vs 2.21 ± 1.04 ng/mL, P < 0.001). After achieving euthyroidism by thionamide treatment, serum Nrg4 levels dropped markedly from 3.57 ± 1.26 to 1.94 ± 0.72 ng/ml (P < 0.001). After adjustment for potential confounders, serum Nrg4 levels were independently associated with hyperthyroidism. The upregulation of Nrg4 expression in the livers and white adipose tissues by T3 was further confirmed by animal and cell culture experiments. Conclusions Serum Nrg4 levels were increased in patients with hyperthyroidism. The liver and white adipose tissue might be primary sources contributing to elevated serum Nrg4 concentrations.

show abstract

Decreased plasma neuregulin 4 concentration is associated with increased high-sensitivity C-reactive protein in newly diagnosed type 2 diabetes mellitus patients: a cross-sectional study

Cited by 24 publications

References 38 publications

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

A systematic review of the association of neuregulin 4, a brown fat–enriched secreted factor, with obesity and related metabolic disturbances

ErbB4 deletion predisposes to development of metabolic syndrome in mice

Elevated serum neuregulin 4 levels in patients with hyperthyroidism

Contact Info

Product

Resources

About