Role of adipokines, oxidative stress, and endotoxins in the pathogenesis of non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus

Background: Type 2 diabetes mellitus (T2DM) is associated with chronic inflammation and oxidative stress, implicated in the pathophysiology of non-alcoholic fatty liver disease (NAFLD). Present study aimed to assess the role of adipokines, oxidative stress, and endotoxins in the pathogenesis of NAFLD in T2DM.Methods: Present cross-sectional observational study included healthy controls (n=50; group 1); T2DM patients without NAFLD (n=50; group 2), T2DM patients with NAFLD (n=50; group 3). Study subjects were age and gender matched.Results: Tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high sensitive C-reactive protein (hs-CRP), endotoxin, malondialdehyde (MDA) were significantly elevated and adiponectin, ferric reducing ability of plasma (FRAP), and glutathione (GSH) were significantly lower (p<0.001) in T2DM patients with NAFLD when compared to T2DM patients without NAFLD and controls. Endotoxin showed significant positive correlation with TNF-α (r=0.304; p<0.001), hs-CRP (r=0.193; p=0.018), and MDA (r=0.420; p<0.001), and significant negative correlation with adiponectin (r=-0.406; p<0.001). TNF-α and IL-6 showed significant positive correlation with MDA (r=0.526; p<0.001, r=0.229; p=0.005) and significant negative correlation with adiponectin (r=-0.396; p<0.001, r=-0.318; p<0.001), FRAP (r=-0.418; p<00.001, r=-0.170; p=0.038), and GSH (r=-0.353; p<0.001, r=-0.301; p<0.001).Conclusions: Authors observed elevated endotoxin, oxidative stress, inflammation and lower adiponectin levels in T2DM subjects compared to controls. These changes were more pronounced in T2DM with NAFLD when compared to T2DM without NAFLD. Lower adiponectin levels were found to be a better predictor of NALFD in T2DM and is associated with oxidative stress and systemic inflammation.

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Non-Alcoholic Steatohepatitis (NASH) and Organokines: What Is Now and What Will Be in the Future

International Journal of Molecular Sciences ◽

10.3390/ijms23010498 ◽

2022 ◽

Vol 23 (1) ◽

pp. 498

Author(s):

João Paulo Margiotti dos Santos ◽

Mariana Canevari de Maio ◽

Monike Alves Lemes ◽

Lucas Fornari Laurindo ◽

Jesselina Francisco dos Santos Haber ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Alcoholic Steatohepatitis ◽

Endocrine Organs ◽

Alcoholic Fatty Liver Disease ◽

Lobular Inflammation

Non-alcoholic steatohepatitis (NASH) is characterized by steatosis, lobular inflammation, and enlargement of the diameter of hepatocytes (ballooning hepatocytes), with or without fibrosis. It affects 20% of patients with non-alcoholic fatty liver disease (NAFLD). Due to liver dysfunction and the numerous metabolic changes that commonly accompany the condition (obesity, insulin resistance, type 2 diabetes, and metabolic syndrome), the secretion of organokines is modified, which may contribute to the pathogenesis or progression of the disease. In this sense, this study aimed to perform a review of the role of organokines in NASH. Thus, by combining descriptors such as NASH, organokines, oxidative stress, inflammation, insulin resistance, and dyslipidemia, a search was carried out in the EMBASE, MEDLINE-PubMed, and Cochrane databases of articles published in the last ten years. Insulin resistance, inflammation and mitochondrial dysfunction, fructose, and intestinal microbiota were factors identified as participating in the genesis and progression of NASH. Changes in the pattern of organokines secretion (adipokines, myokines, hepatokines, and osteokines) directly or indirectly contribute to aggravating the condition or compromise homeostasis. Thus, further studies involving skeletal muscle, adipose, bone, and liver tissue as endocrine organs are essential to better understand the modulation of organokines involved in the pathogenesis of NASH to advance in the treatment of this disease.

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The Role of Oxidative Stress in NAFLD–NASH–HCC Transition—Focus on NADPH Oxidases

Biomedicines ◽

10.3390/biomedicines9060687 ◽

2021 ◽

Vol 9 (6) ◽

pp. 687

Author(s):

Daniela Gabbia ◽

Luana Cannella ◽

Sara De De Martin

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Current Knowledge ◽

Mechanisms Of Action ◽

Nadph Oxidases ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

A peculiar role for oxidative stress in non-alcoholic fatty liver disease (NAFLD) and its transition to the inflammatory complication non-alcoholic steatohepatitis (NASH), as well as in its threatening evolution to hepatocellular carcinoma (HCC), is supported by numerous experimental and clinical studies. NADPH oxidases (NOXs) are enzymes producing reactive oxygen species (ROS), whose abundance in liver cells is closely related to inflammation and immune responses. Here, we reviewed recent findings regarding this topic, focusing on the role of NOXs in the different stages of fatty liver disease and describing the current knowledge about their mechanisms of action. We conclude that, although there is a consensus that NOX-produced ROS are toxic in non-neoplastic conditions due to their role in the inflammatory vicious cycle sustaining the transition of NAFLD to NASH, their effect is controversial in the neoplastic transition towards HCC. In this regard, there are indications of a differential effect of NOX isoforms, since NOX1 and NOX2 play a detrimental role, whereas increased NOX4 expression appears to be correlated with better HCC prognosis in some studies. Further studies are needed to fully unravel the mechanisms of action of NOXs and their relationships with the signaling pathways modulating steatosis and liver cancer development.

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Non-alcoholic fatty liver disease and metabolic syndrome in childhood

Experimental and Clinical Gastroenterology ◽

10.31146/1682-8658-ecg-183-11-51-61 ◽

2020 ◽

Vol 183 (11) ◽

pp. 51-61

Author(s):

N. N. Vlasov ◽

E. A. Kornienko

Keyword(s):

Metabolic Syndrome ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Lifestyle Changes ◽

Alcoholic Fatty Liver ◽

Ample Evidence ◽

Alcoholic Fatty Liver Disease

There is ample evidence that insulin resistance, hyperinsulinemia, and obesity are at the heart of the development of non-alcoholic fatty liver disease (NAFLD). The disease is now considered as the hepatic component of metabolic syndrome (MS).64 children with NAFLD were assessed for metabolic syndrome stigma. An analysis was also made on the state of the problem according to the literature on the general links of the pathogenesis of these conditions, methods of diagnosis and treatment of NAFLD.All components of MS are observed with diﬀerent frequencies in patients with NAFD. This disease, together with type 2 diabetes mellitus, becomes very common diseases in childhood. The incidence of NAFLD in children is constantly growing, it has begun to occur in infants, an outcome in cirrhosis of the liver is possible within childhood, although the prognosis for NAFLD remains deﬁnitely uncertain. Weight loss with a low glycemic index diet, regular exercise, and other lifestyle changes are the mainstay of NAFLD treatment, but not yet very eﬀective for various reasons. In these conditions, it is necessary to increase the role of primary prevention of MS and NAFLD.

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The crucial role of oxidative stress in non-alcoholic fatty liver disease-induced male reproductive toxicity: the ameliorative effects of Iranian indigenous probiotics

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/s00210-021-02177-0 ◽

2022 ◽

Author(s):

Mohammad Mehdi Ommati ◽

Huifeng Li ◽

Akram Jamshidzadeh ◽

Fereshteh Khoshghadam ◽

Socorro Retana-Márquez ◽

...

Keyword(s):

Oxidative Stress ◽

Liver Disease ◽

Fatty Liver ◽

Crucial Role ◽

Fatty Liver Disease ◽

Reproductive Toxicity ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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Microbiota, type 2 diabetes and non-alcoholic fatty liver disease: protocol of an observational study

Journal of Translational Medicine ◽

10.1186/s12967-019-02130-z ◽

2019 ◽

Vol 17 (1) ◽

Cited By ~ 1

Author(s):

Benedetta M. Motta ◽

Christoph Grander ◽

Martin Gögele ◽

Luisa Foco ◽

Vladimir Vukovic ◽

...

Keyword(s):

Type 2 Diabetes ◽

Liver Disease ◽

Fatty Liver Disease ◽

Liver Stiffness ◽

Alcoholic Fatty Liver ◽

Study Participants ◽

The Relationship ◽

Alcoholic Fatty Liver Disease

Abstract Background Non-alcoholic fatty liver disease (NAFLD) is characterized by triglyceride accumulation in the hepatocytes in the absence of alcohol overconsumption, commonly associated with insulin resistance and obesity. Both NAFLD and type 2 diabetes (T2D) are characterized by an altered microbiota composition, however the role of the microbiota in NAFLD and T2D is not well understood. To assess the relationship between alteration in the microbiota and NAFLD while dissecting the role of T2D, we established a nested study on T2D and non-T2D individuals within the Cooperative Health Research In South Tyrol (CHRIS) study, called the CHRIS-NAFLD study. Here, we present the study protocol along with baseline and follow-up characteristics of study participants. Methods Among the first 4979 CHRIS study participants, 227 individuals with T2D were identified and recalled, along with 227 age- and sex-matched non-T2D individuals. Participants underwent ultrasound and transient elastography examination to evaluate the presence of hepatic steatosis and liver stiffness. Additionally, sampling of saliva and faeces, biochemical measurements and clinical interviews were carried out. Results We recruited 173 T2D and 183 non-T2D participants (78% overall response rate). Hepatic steatosis was more common in T2D (63.7%) than non-T2D (36.3%) participants. T2D participants also had higher levels of liver stiffness (median 4.8 kPa, interquartile range (IQR) 3.7, 5.9) than non-T2D participants (median 3.9 kPa, IQR 3.3, 5.1). The non-invasive scoring systems like the NAFLD fibrosis score (NFS) suggests an increased liver fibrosis in T2D (mean − 0.55, standard deviation, SD, 1.30) than non-T2D participants (mean − 1.30, SD, 1.17). Discussion Given the comprehensive biochemical and clinical characterization of study participants, once the bioinformatics classification of the microbiota will be completed, the CHRIS-NAFLD study will become a useful resource to further our understanding of the relationship between microbiota, T2D and NAFLD.

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Non-alcoholic fatty liver disease: the role of the nurse

Gastrointestinal Nursing ◽

10.12968/gasn.2020.18.sup6.s15 ◽

2020 ◽

Vol 18 (Sup6) ◽

pp. S15-S21

Author(s):

Lea Ladegaard Grønkjær ◽

Charlotte Wernberg ◽

Mette Munk Lauridsen

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Western World ◽

Alcoholic Fatty Liver ◽

Obesity Epidemic ◽

Adults And Children ◽

Alcoholic Fatty Liver Disease

Obesity is a frequent cause of morbidity in the Western world, and its prevalence has doubled since 1980. It is well known that conditions such as cardiovascular disease and type 2 diabetes can be serious consequences of obesity. However, less is known about whether the liver may also be affected by the obesity epidemic. Non-alcoholic fatty liver disease (NAFLD) is present in more than a quarter of the adult Western population, and the prevalence is increasing among both adults and children. NAFLD thus represents a common liver disease in the Western world. This is worrisome, because NAFLD can cause liver inflammation and various stages of fibrosis and eventually result in cirrhosis and hepatocellular carcinoma, which both have a high mortality rate due to related complications. Lifestyle change is the most important aspect in the prevention and treatment of NAFLD, and nurses play an important role in the early detection of NAFLD and the prevention of its possible progression.

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Frequency and risk factors associated with non-alcoholic fatty liver disease in patients with type 2 diabetes mellitus

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/s0004-27302010000400004 ◽

2010 ◽

Vol 54 (4) ◽

pp. 362-368 ◽

Cited By ~ 21

Author(s):

Vera S. G. Ferreira ◽

Ricardo B. Pernambuco ◽

Edmundo P. Lopes ◽

Clarice N. Morais ◽

Marbiana C. Rodrigues ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Uric Acid ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Tnf Α ◽

Alcoholic Fatty Liver Disease

OBJECTIVE: To evaluate the frequency of non-alcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (DM2) and to describe its risk factors. SUBJECTS AND METHODS: Blood samples of 78 patients were collected for assessment of glycemic and lipid profile, liver enzymes, TNF-α and HOMA-IR. The diagnosis of NAFLD was established by ultrasound. RESULTS: NAFLD was observed in 42% of patients who had greater BMI (p < 0.001), and frequency of hypertension (p < 0.001). Metabolic syndrome was more frequent in those with NAFLD (p = 0.019). The levels of aspartate, alanine aminotransferase, γ-glutamyl transpeptidase, uric acid, TNF-α, insulin and HOMA-IR were significantly higher in patients with NAFLD than those without NAFLD. CONCLUSION: Almost half of patients with DM2 were found to have NAFLD, and they have more elevated BMI, as well as higher levels of aminotransferases, γ-GT, uric acid, TNF-α, insulin and HOMA-IR than subjects without NAFLD.

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Mo1016 Role of Oxidative Stress and Insulin Resistance in the Disease Severity of Non-Alcoholic Fatty Liver Disease

Gastroenterology ◽

10.1016/s0016-5085(13)63763-4 ◽

2013 ◽

Vol 144 (5) ◽

pp. S-1013

Author(s):

Billur Canbakan ◽

Hakan Senturk ◽

Murat Tuncer ◽

Ibrahim Hatemi ◽

Emine Koroglu ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Liver Disease ◽

Fatty Liver ◽

Disease Severity ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Alcoholic Fatty Liver Disease

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Serum Levels of Oxidative Stress Markers in Patients with Type 2 Diabetes Mellitus and Non-alcoholic Steatohepatitis

Romanian Journal of Internal Medicine ◽

10.1515/rjim-2016-0035 ◽

2016 ◽

Vol 54 (4) ◽

pp. 228-236 ◽

Cited By ~ 5

Author(s):

F. Casoinic ◽

D. Sampelean ◽

Anca D. Buzoianu ◽

N. Hancu ◽

Dorina Baston

Keyword(s):

Oxidative Stress ◽

Fatty Liver Disease ◽

Serum Levels ◽

Protein Carbonyls ◽

Oxidative Stress Markers ◽

Multivariate Logistic Regression ◽

Alcoholic Fatty Liver ◽

Stress Markers ◽

Alcoholic Fatty Liver Disease

Abstract Introduction. Oxidative stress is one of the key mechanisms responsible for disease progression in non-alcoholic fatty liver disease. The aim of this study was to evaluate the serum levels of oxidative stress markers in patients with type 2 diabetes mellitus (DMT2) and non-alcoholic steatohepatitis (NASH) and test their relationships with clinical and biochemical patient characteristics, compared to patients with DMT2 without non-alcoholic fatty liver disease (NAFLD), and controls. Materials and methods. In all, 60 consecutive patients with DMT2 and NASH, 55 with DMT2 without NAFLD, and 50 age-and-gender-matched healthy subjects participated in the study. The serum levels of protein carbonyls and 8-isoprostane were determined by ELISA methods, while the serum levels of malondialdehyde (MDA) were detected by means of the spectrophotometric method. Clinical, demographic, and laboratory parameters were examined for all the subjects included in the study. Multivariate logistic regression was used to test the independent predictive factors in the relationships investigated here. Results. Patients with DMT2 and NASH displayed significantly higher serum levels of protein carbonyls (1.112 ± 0.42 nmol/dL), MDA (6.181 ± 1.81 ng/mL), and 8-isoprostane (338.6 ± 98.5 pg/mL) compared to patients with DMT2 without NAFLD, and controls. Results of multivariate logistic regression analyses indicate that in patients with DMT2 and NASH, the serum levels of oxidative stress markers were independently and positively associated with: HbA1c, duration of diabetes, the UKPDS cardiovascular risk score (for protein carbonyls); age, LDL-cholesterol (for 8-isoprostane); and triglycerides serum levels (for MDA). Conclusions. Our findings indicate that the process of oxidative stress tends to increase in patients with DMT2 and NASH, compared to patients with DMT2 without NAFLD, and controls. This evidence suggests that an antioxidant therapy might prove useful in the treatment of patients with DMT2 and NASH.

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