Insulin resistance and NAFLD: Relationship with intrahepatic iron and serum TNF-α using 1H MR spectroscopy and MRI

Martín-Rodríguez, José Luis; González‐Cantero, Álvaro; Martí‐Bonmatí, Luis; Alberich‐Bayarri, Ángel; González-Cejudo, Trinidad; González-Calvin, Jorge L.

doi:10.1016/j.diabet.2019.01.005

Cited by 17 publications

(12 citation statements)

References 37 publications

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“…The chronic low-grade inflammatory state of PCOS is closely associated with the occurrence of IR. According to previous studies, the level of most low-grade chronic inflammation markers, such as TNF-α, CRP, and IL-6, is positively correlated with IR and circulating insulin levels [33]. Inflammatory factors stimulate serine, leading to increased levels of phosphorylation, inhibited tyrosine kinase activity, and decreased levels of insulin-stimulated receptor tyrosine phosphorylation, impeding insulin receptor signaling, and reducing IRS-1 activity.…”

Section: Discussionmentioning

confidence: 98%

PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

et al. 2020

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Background: Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder, and its pathogenesis is still under debate. Trimethylamine-N-oxide (TMAO) is a small, organic compound generated by the gut microbiome with a hypothesized relation to insulin resistance (IR) and low-grade inflammation in PCOS. By comparing plasma TMAO levels in non-PCOS participants and PCOS patients without hyperandrogenism (HA), we aimed to determine whether plasma TMAO levels correlate with PCOS without HA and to analyze their relationship with low-grade inflammation and IR. Methods: A total of 27 PCOS patients without HA and 23 non-PCOS participants were enrolled in this study and subdivided into "nonobese" and "obese" arms for each group. Levels of plasma TMAO were quantified, and basic clinical characteristics and plasma biomarkers of inflammation were assessed. Results: First, plasma TMAO levels, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) values were higher in PCOS patients without HA, especially in the obese subgroup. Second, the levels of the inflammatory factors interleukin (IL)-17A, IL-18 and interferon gamma (IFN-γ) were significantly increased in obese PCOS patients without HA. Third, plasma TMAO levels were associated with body mass index (BMI) in the normalweight groups, and the obese groups had higher fasting plasma insulin (FINS) and HOMA-IR values. Finally, logistic regression showed that the plasma levels of TMAO and luteinizing hormone/follicle-stimulating hormone (LH/FSH) were independent predictors of PCOS and indicated an increased risk of PCOS. Conclusions: Elevated plasma TMAO levels may be associated with the pathogenesis of PCOS without HA and correlated with increased systemic inflammation. Further studies are needed to determine the suitability of TMAO as a predictive biomarker and to identify possible therapies for PCOS.

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Section: Discussionmentioning

confidence: 98%

PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

et al. 2020

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“…By inhibiting insulin signaling, TNF‐α overexpression is regarded as a key mechanism linking obesity with insulin resistance (IR) 8 . High serum TNF‐α concentrations may contribute to the association between NAFLD, IR, 9 and cardiovascular risk, 10 thus implying a connection between subclinical inflammatory state and metabolic disorders 8 . The above considering, higher TNF‐α levels are expected when NAFLD progresses.…”

Section: Introductionmentioning

confidence: 99%

Circulating tumor necrosis factor‐α levels in non‐alcoholic fatty liver disease: A systematic review and a meta‐analysis

Potoupni

Georgiadou

Chatzigriva

et al. 2021

J of Gastro and Hepatol

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Background and Aim To synthesize data on circulating tumor necrosis factor (TNF)‐α levels between patients with histologically confirmed non‐alcoholic fatty liver disease (NAFLD) (simple steatosis or non‐alcoholic fatty liver [NAFL] and/or non‐alcoholic steatohepatitis [NASH]) and controls. Methods We performed a systematic search in PubMed, Scopus, and Cochrane Library. Fifty‐six studies, published between 2003 and 2019, were finally included, reporting data from 5848 individuals (1634 controls and 4214 NAFLD patients). Results Higher circulating TNF‐α levels were observed in NAFLD patients than controls (standardized mean difference [SMD] 0.84; 95% confidence interval [95% CI] 0.59–1.09), NAFL patients than controls (SMD 0.56; 95% CI 0.27–0.85), NASH patients than controls (SMD 0.93; 95% CI 0.64–1.22), and NASH than NAFL patients (SMD 0.31; 95% CI 0.16–0.46). There were only minimal changes in the comparisons between groups after excluding studies with morbidly obese populations (n = 11), or pediatric/adolescent populations (n = 6), or other than enzyme‐linked immunosorbent assay method of TNF‐α measurement (n = 8). There was high heterogeneity among studies in all comparisons, which was not essentially affected after sensitivity analyses. The meta‐regression analysis revealed that the male ratio was positively associated with TNF‐α SMD in the comparison between patients with NASH and NAFL (beta = 0.809; 95% CI 0.052–1.566) and accounted for 36% (P = 0.037) of the heterogeneity in this pair of comparison. TNF‐α SMD was not associated with age, body mass index, and alanine aminotransferase in any pair of comparisons. Conclusions Circulating TNF‐α levels were higher in patients with NAFLD compared with controls. Higher levels of circulating TNF‐α were also associated with the severity of NAFLD.

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“…Accordingly, it is known that iron-overload increases serum triglycerides associated with fatty liver in experimental animals [ 38 ]. NAFLD patients also show an increase of both triglycerides and iron in the liver [ 39 ], and that iron stores as ferritin in NAFLD is associated with hypertriglyceridemia [ 40 ]. Iron overload can also affect visceral adipose tissue metabolism by a mechanism involving hepcidin up-regulation [ 41 ].…”

Section: Discussionmentioning

confidence: 99%

Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary hemochromatosis

et al. 2020

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Background Hereditary hemochromatosis (HH) is an autosomal recessive genetic disorder with increased intestinal iron absorption and therefore iron Overloa d. iron overload leads to increased levels of toxic non-transferrin bound iron which results in oxidative stress and lipid peroxidation. The impact of iron on lipid metabolism is so far not fully understood. The aim of this study was to investigate lipid metabolism including lipoproteins (HDL, LDL), neutral (triglycerides, cholesterol) and polar lipids (sphingo- and phospholipids), and PNPLA3 polymorphism (rs738409/I148M) in HH. Methods We conducted a cohort study of 54 subjects with HH and 20 healthy subjects. Patients were analyzed for their iron status including iron, ferritin, transferrin and transferrin saturation and serum lipid profile on a routine follow-up examination. Results HH group showed significantly lower serum phosphatidylcholine (PC) and significantly higher phosphatidylethanolamine (PE) compared to healthy control group. The ratio of PC/PE was clearly lower in HH group indicating a shift from PC to PE. Triglycerides were significantly higher in HH group. No differences were seen for HDL, LDL and cholesterol. Hepatic steatosis was significantly more frequent in HH. PNPLA3 polymorphism (CC vs. CG/GG) did not reveal any significant correlation with iron and lipid parameters including neutral and polar lipids, grade of steatosis and fibrosis. Conclusion Our study strengthens the hypothesis of altered lipid metabolism in HH and susceptibility to nonalcoholic fatty liver disease. Disturbed phospholipid metabolism may represent an important factor in pathogenesis of hepatic steatosis in HH.

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Insulin resistance and NAFLD: Relationship with intrahepatic iron and serum TNF-α using 1H MR spectroscopy and MRI

Cited by 17 publications

References 37 publications

PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

PCOS without hyperandrogenism is associated with higher plasma Trimethylamine N-oxide levels

Circulating tumor necrosis factor‐α levels in non‐alcoholic fatty liver disease: A systematic review and a meta‐analysis

Plasma Lipidome, PNPLA3 polymorphism and hepatic steatosis in hereditary hemochromatosis

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