Osteocalcin and osteoprotegerin levels and their relationship with adipokines and proinflammatory cytokines in children with nonalcoholic fatty liver disease

Amrousy, Doaa El; El-Afify, Dalia

doi:10.1016/j.cyto.2020.155215

Cited by 17 publications

(12 citation statements)

References 37 publications

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“…Future cohort or intervention studies should be conducted to verify the findings. Thirdly, osteocalcin produces a widespread increase in insulin sensitivity, and it could be a potential mediator in the production of adiponectin by adipose tissue [74]. This could be a potential research direction for our future studies, but unfortunately, we did not have the data of osteocalcin in the present study.…”

Section: Discussionmentioning

confidence: 83%

Mediating Roles of hsCRP, TNF-α and Adiponectin on the Associations between Body Fat and Fatty Liver Disease among Overweight and Obese Adults

Xie

Tang

et al. 2021

Biology

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Body fat has been reported to be associated with a higher risk of fatty liver disease (FLD). However, few studies have explored the mediating roles of an inflammatory biomarker or adipokine on the relationships. Here, we examined the potential mediating roles of high sensitivity C-reactive protein (hsCRP), tumor necrosis factor-α (TNF-α) and adiponectin (APN) in relationships between body fat and FLD in overweight and obese adults. Additionally, gender differences will be investigated. In total, 1221 participants aged 19–56 years were included in our study. Body fat percentage was measured with Dual Energy X-ray Absorptiometry (DEXA) and FLD by abdominal ultrasound. Mediation analysis was performed to assess the mediating effect of hsCRP, TNF-α and APN on the associations between BF (%) and FLD by gender differences. We found that hsCRP was significantly associated with body fat percentage in both genders (b = 0.2014, p < 0.0001and b = 0.1804, p < 0.0001 for male and female, respectively), while hsCRP was associated with FLD only in the female group (b = 0.1609, p = 0.0109) but not in male group (b = 0.4800, p = 0.0603). We observed that hsCRP has a significant mediating effect on the association between body fat percentage and FLD (b = 0.0290, p = 0.0201, mediation ratio: 13.6%) in the female group independent of potential covariates (age, smoking, alcohol drinking and physical activity). TNF-α was not significantly associated with body fat percentage or FLD, with no mediating effect on the association between body fat percentage and FLD in either gender. In conclusion, there is a gender-specific mediation role of hsCRP in the association between body fat and FLD. HsCRP was a potential mediator on the association between adiposity and FLD in the female gender, but not in the male gender. Higher body fat was associated with a higher risk of FLD, and the inflammation level might play a potential mediating role in the association between body fat and FLD among female overweight and obese adults.

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Section: Discussionmentioning

confidence: 83%

Mediating Roles of hsCRP, TNF-α and Adiponectin on the Associations between Body Fat and Fatty Liver Disease among Overweight and Obese Adults

Xie

Tang

et al. 2021

Biology

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“…In the present study, we found that the hepatocyte OPG level was signi cantly decreased in patients with NASH, NASH animal models, and cellular models. Most clinical studies have shown decreased circulating-OPG levels in patients with NASH 12,15,16 ; however, a few studies have reported increased OPG levels 17 . These differences may be attributed to factors including ethnicity, different diagnostic criteria, and different manufacturers of test kits.…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that OPG may be a key mediator of communication between the liver and bone tissues and between NAFLD and osteoporosis development. However, the role of OPG in NASH is not fully understood, and although some clinical studies have shown that OPG levels are signi cantly reduced in adults and children with NASH 12,13 , the underlying mechanism is unclear. Based on previous studies showing that OPG can regulate apoptosis and in ammation-related signals via several pathways including RANKL and TNF-related apoptosis-inducing ligand (TRAIL), we hypothesized that OPG could affect NASH progression by regulating in ammatory signals 14 .…”

Section: Introductionmentioning

confidence: 99%

Osteoprotegerin deficiency aggravates methionine- choline- deficient diet-induced nonalcoholic steatohepatitis in mice

Lin

Ruan

et al. 2022

Preprint

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Background & Aims: Clinical studies have shown that osteoprotegerin (OPG) is reduced in patients with nonalcoholic steatohepatitis (NASH), but the underlying mechanisms are unclear. The current study focuses on the role of OPG in the NASH pathogenesis. Methods OPG knockout mice and wild-type control mice fed a methionine choline-deficient diet (MCD) for 4 weeks resulted in an animal model of NASH. Measurement of triglycerides (TG) in serum and liver to assess steatosis. Hematoxylin eosin (HE), Sirius Red and Masson staining were used to assess the liver damage. Transcriptome sequencing analysis, qPCR and western blot were to analyze changes in lipid metabolism and inflammation-related indicators in the liver. Results In vivo knockout of OPG resulted in a reduction of TG levels in the liver and a significant increase in serum ALT and AST. The expression of inflammatory factors and fibrosis genes was significantly upregulated in the livers of OPG knockout mice. Transcriptome sequencing analysis showed that OPG knockout significantly enhanced MCD diet-induced activation of the mitogen-activated protein kinase (MAPK) signaling pathway. Mechanistically, OPG may inhibit MAPK signaling pathway activity by upregulating the expression of dual specificity phosphatase 14 (DUSP14), thereby reducing inflammatory injury. Conclusion OPG may be a drug target for the treatment of NASH.

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“…The negative correlations of serum OCN levels with ALT and γ-GT have also been reported by several previous studies. 13,[45][46][47] Also, a previous study showed that low levels of serum OCN were associated with liver fibrosis in morbidly obese patients, 48 indicating that serum OCN levels might reflect not only the presence but also the severity of MAFLD. In fact, experiments in animal models have provided confirming evidence that OCN treatment alleviates hepatic steatosis by reducing hepatic expression of sterol regulatory element-binding proteins (SREBP-1) and its downstream proteins in wild-type mice fed with Western diet, which play an important role in hepatic lipogenesis and TG accumulation.…”

mentioning

confidence: 99%

Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes

Wang¹,

Jin²,

Ke³

et al. 2022

DMSO

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Purpose The association between serum osteocalcin (OCN) levels and metabolic dysfunction-associated fatty liver disease (MAFLD) is still controversial. Moreover, few studies have explored their relationship in type 2 diabetes mellitus (T2DM) patients so far. The present study aimed to investigate the association of serum OCN levels with MAFLD in Chinese T2DM patients. Methods This cross-sectional, real-world study included 1889 Chinese T2DM inpatients. MAFLD was diagnosed by abdominal ultrasonography. Participants were divided into four groups according to serum OCN quartiles, among which the clinical characteristics were compared. The association of serum OCN levels with the presence of MAFLD was also analyzed in subjects. Results After controlling for sex, age, and diabetes duration, the prevalence of MAFLD significantly decreased across the serum OCN quartiles (55.3%, 52.0%, 48.6%, and 42.1% for the first, second, third, and fourth quartiles, respectively, P < 0.001 for trend). A fully adjusted multiple logistic regression analysis showed that serum OCN levels were independently and negatively associated with the presence of MAFLD in T2DM patients (odds ratio, 0.832; 95% confidence interval, 0.719–0.962; P = 0.013). Furthermore, there were significant decreases in HOMA-IR (P = 0.001 for trend) and C-reactive protein (P < 0.001 for trend) levels across the serum OCN quartiles after controlling for sex, age, and diabetes duration. Conclusion Serum OCN levels were independently and negatively associated with the presence of MAFLD in Chinese T2DM patients, partially due to the improvement of insulin resistance and inflammation mediated by OCN. Serum OCN may be used as a biomarker to assess the risk of MAFLD in T2DM patients.

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Osteocalcin and osteoprotegerin levels and their relationship with adipokines and proinflammatory cytokines in children with nonalcoholic fatty liver disease

Cited by 17 publications

References 37 publications

Mediating Roles of hsCRP, TNF-α and Adiponectin on the Associations between Body Fat and Fatty Liver Disease among Overweight and Obese Adults

Mediating Roles of hsCRP, TNF-α and Adiponectin on the Associations between Body Fat and Fatty Liver Disease among Overweight and Obese Adults

Osteoprotegerin deficiency aggravates methionine- choline- deficient diet-induced nonalcoholic steatohepatitis in mice

Decreased Serum Osteocalcin is an Independent Risk Factor for Metabolic Dysfunction-Associated Fatty Liver Disease in Type 2 Diabetes

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