scholarly journals Chronic exposure to IL6 leads to deregulation of glycolysis and fat accumulation in the zebrafish liver

2020 ◽  
Author(s):  
Manoj K Singh ◽  
Rijith Jayarajan ◽  
Swati Varshney ◽  
Sindhuri Upadrasta ◽  
Archana Singh ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Glycolytic Enzyme ◽  
Transgenic Zebrafish ◽  
Causative Role ◽  
Hereditary Fructose Intolerance ◽  
Alcoholic Fatty Liver ◽  
Aldolase B ◽  
Intrahepatic Lipid

AbstractBACKGROUND AND AIMSInflammation is a constant in Non-Alcoholic Fatty Liver Disease (NAFLD) and is usually considered a consequence. We propose that inflammation can be a cause for NAFLD. Obesity is strongly associated with (NAFLD), but not always. NAFLD in lean individuals is more common in certain populations, especially Asian-Indians. Lean healthy Indians also have a higher basal circulating IL6 suggesting a link with inflammation. We propose that inflammation-induced fatty liver could be relevant for studying obesity-independent NAFLD. Commonly used high-fat diet-induced NAFLD animal models are not ideal for testing this hypothesis.APPROACH AND RESULTSIn this study we used a transgenic zebrafish with chronic systemic overexpression of human IL6 (IL6-OE) and found accumulation of triglyceride in the liver. We performed comparative transcriptomics and proteomics on the IL6-OE liver and found an expression signature distinct from the diet-based NAFLD models. We discovered a deregulation of glycolysis/gluconeogenesis pathway, especially a robust down regulation of the glycolytic enzyme aldolase b in the IL6-OE liver. Metabolomics of the IL6-OE liver showed accumulation of hexose monophosphates and their derivatives, which can act as precursors for triglyceride synthesis. Patients with the genetic disease Hereditary Fructose Intolerance (HFI) caused by ALDOLASE B deficiency also have a higher propensity to develop fatty liver disease.CONCLUSIONSOur study demonstrates a causative role for inflammation in intrahepatic lipid accumulation. Further, our results suggest that IL6-driven repression of glycolysis/gluconeogenesis, specifically aldolase b, may be a novel mechanism for development of fatty liver, especially in obesity-independent NAFLD.

Circulating CD36 Correlates with Intrahepatic Lipid Content in Non-Alcoholic Fatty Liver Disease Patients

2016 ◽  
Vol 64 (2) ◽  
pp. S497
Author(s):  
S. Heebøll ◽  
M.K. Poulsen ◽  
M.J. Ørnstrup ◽  
T.N. Kjær ◽  
S.B. Pedersen ◽  
...  
Keyword(s):  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Content ◽  
Fatty Liver Disease ◽  
Alcoholic Fatty Liver ◽  
Intrahepatic Lipid ◽  
Alcoholic Fatty Liver Disease

scholarly journals Leptin, free leptin index, insulin resistance and liver fibrosis in children with non-alcoholic fatty liver disease

2006 ◽  
Vol 155 (5) ◽  
pp. 735-743 ◽  
Author(s):  
Valerio Nobili ◽  
Melania Manco ◽  
Paolo Ciampalini ◽  
Vincenzo Diciommo ◽  
Rita Devito ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Glucose Tolerance ◽  
Fatty Liver ◽  
Fatty Liver Disease ◽  
Sensitivity Index ◽  
Causative Role ◽  
Alcoholic Fatty Liver ◽  
Nas Score ◽  
Alcoholic Fatty Liver Disease

Objective: Prevalence of non-alcoholic fatty liver disease (NAFLD) among children is increasing dramatically. It is unclear why some patients develop steatohepatitis (NASH), fibrosis and cirrhosis from steatosis, and others do not. A role for leptin has been claimed. This study aims to evaluate the relationship between leptin, insulin resistance (IR) and NAFLD in children. Design and methods: In 72 biopsy-proven NAFLD children (aged 9–18 years; 51M/21F), fasting leptin and its soluble receptor (sOB-R) were measured; free leptin index (FLI) was calculated as leptin/sOB-R; IR was estimated by homeostasis model assessment (HOMA-IR) and insulin sensitivity index (ISI-comp); glucose tolerance by oral glucose tolerance test (OGTT). Percentage of total body fat (TBF) by dual-energy X-ray absorptiometry (DXA) was available in 65 patients. Results: Prevalence of diabetes, impaired fasting and/or after load glucose tolerance was 11%. HOMA-IR and ISI-comp values were 2.55 ± 1.39 and 4.4 ± 2. NASH was diagnosed in 38 and simple steatosis in 25 children; diagnosis was indeterminate in 29 children. Increased fibrosis, mostly of mild severity, was observed in 41 patients. Median NAFLD activity (NAS) score was 3.42 ± 1.60. According to histology, levels of leptin and FLI increased as steatosis (leptin from 11.9 ± 6.3 in score 1 to 17.4 ± 6.9 in score 2 (P = 0.01) and 22.2 ± 6.8 ng/ml in score 3 (P < 0.001); FLI 2.56 ± 1.40, 3.57 ± 0.34, 4.45 ± 0.64 respectively (P = 0.05)); ballooning (from 13.7 ± 6.7 in score 1 to 17 ± 7.5 in score 2 (P = 0.001) and 22.1 ± 7.1 ng/ml in score 3 (P = 0.01); FLI 2.81 ± 1.50, 3.40 ± 1.65, 4.57 ± 1.67 (P = 0.01 between 0 and 2)); fibrosis (from 14.3 ± 7 to18.3 ± 6.9; P = 0.03; FLI 3.03 ± 1.57 vs 3.92 ± 077; P < 0.05) and NAS score (score 1–2: 12.9 ± 6.9; score 3–4: 17 ± 6.9 (P = 0.01); score 5–7: 22.9 ± 7.5 ng/ml (P = 0.03); FLI 2.70 ± 1.53, 3.12 ± 1.53, 4.58 ± 1.57 P = 0.01 and P = 0.05 between 1–2 vs 3–4 and 3–4 vs 5–7 respectively) worsened. Higher leptin correlated with more severe steatosis, ballooning and NAS score (r0 = 0.6, 0.4 and 0.6 respectively; for all P < 0.001); FLI with ballooning (r0 = 0.4, P < 0.0001), steatosis (r0 = 0.5, P < 0.0001) and NAS score (r0 = 0.5, P < 0.0001). Conclusions: Leptin and liver injury correlated independently of age, BMI and gender in the present study. Nevertheless, any causative role of leptin in NAFLD progression could be established. Thus, studies are needed to define whether the hormone plays a major role in the disease.

Vitamin D levels are not associated with non-alcoholic fatty liver disease severity in a Brazilian population

2020 ◽  
pp. 1-8
Author(s):  
Jeniffer Danielle M. Dutra ◽  
Quelson Coelho Lisboa ◽  
Silvia Marinho Ferolla ◽  
Carolina Martinelli M. L. Carvalho ◽  
Camila Costa M. Mendes ◽  
...  
Keyword(s):  
Vitamin D ◽  
Liver Disease ◽  
Fatty Liver ◽  
Disease Severity ◽  
Fatty Liver Disease ◽  
Hypovitaminosis D ◽  
Alcoholic Fatty Liver ◽  
Vitamin D Levels ◽  
The Mean ◽  
Alcoholic Fatty Liver Disease

Abstract. Some epidemiological evidence suggests an inverse correlation between non-alcoholic fatty liver disease (NAFLD) frequency and vitamin D levels. Likewise, a beneficial effect of vitamin D on diabetes mellitus (DM) and insulin resistance has been observed, but this is an unsolved issue. Thus, we aimed to investigate the prevalence of hypovitaminosis D in a NAFLD Brazilian population and its association with disease severity and presence of comorbidities. In a cross-sectional study, the clinical, biochemical and histological parameters of 139 NAFLD patients were evaluated according to two different cut-off points of serum 25-hydroxyvitamin D levels (20 ng/mL and 30 ng/mL). The mean age of the population was 56 ± 16 years, most patients were female (83%), 72% had hypertension, 88% dyslipidemia, 46% DM, 98% central obesity, and 82% metabolic syndrome. Serum vitamin D levels were < 30 ng/mL in 78% of the patients, and < 20 ng/mL in 35%. The mean vitamin D level was 24.3 ± 6.8 ng/mL. The comparison between the clinical, biochemical and histological characteristics of the patients according to the levels of vitamin D showed no significant difference. Most patients with NAFLD had hypovitaminosis D, but low vitamin D levels were not related to disease severity and the presence of comorbidities.

Non-Alcoholic Fatty Liver Disease in Overweight Children and its Relationship with Retinol Serum Levels

2008 ◽  
Vol 78 (1) ◽  
pp. 27-32 ◽  
Author(s):  
Suano de Souza ◽  
Silverio Amancio ◽  
Saccardo Sarni ◽  
Sacchi Pitta ◽  
Fernandes ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Lipid Profile ◽  
Fatty Liver Disease ◽  
Thiobarbituric Acid ◽  
Serum Levels ◽  
Control Group ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Objectives: To evaluate the frequency of non-alcoholic fatty liver disease, the retinol serum levels, lipid profile, and insulin resistance in overweight/obese children. To relate these biochemical variables with the risk of this disease in the population studied. Methods: The study was cross-sectional and prospective, with 46 overweight/obese school children (28 female, 18 male; mean age 8.6 years). The control group consisted of 45 children, paired by age and gender. Hepatic steatosis, evaluated by ultrasound, was classified as normal, mild, moderate, or severe. Also evaluated were serum retinol levels; thiobarbituric acid reactive substances; lipid profile; and fasting glucose and serum insulin levels, used for the calculation of the Homeostasis Model Assessment. Results: Hepatic ultrasound alterations were found in 56.5% and 48,9% of the overweight/obese and control group children, respectively. Presence of obesity was associated with high levels of triglycerides (OR = 4.6; P = 0.002). In the studied children, the risk of steatosis was related to a trend to a higher percentage of retinol inadequacy (OR = 2.8; p = 0.051); there was no association with thiobarbituric acid reactive substances, lipid profile, or insulin resistance. Conclusions: The high frequency of non-alcoholic fatty liver disease in both groups, evaluated by hepatic ultrasound, in low-socioeconomic level children, independent of nutritional condition and without significant association with insulin resistance, emphasizes that especially in developing countries, other risk factors such as micronutrient deficiencies (e.g. vitamin A) are involved.

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