scholarly journals Fucoidan and Fucoxanthin Attenuate Hepatic Steatosis and Inflammation of NAFLD through Modulation of Leptin/Adiponectin Axis

Marine Drugs ◽  
2021 ◽  
Vol 19 (3) ◽  
pp. 148
Author(s):  
Ping-Hsiao Shih ◽  
Sheng-Jie Shiue ◽  
Chun-Nan Chen ◽  
Sheng-Wei Cheng ◽  
Hsin-Yi Lin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
Fasting Blood Glucose ◽  
Glycogen Metabolism ◽  
Interferon Γ ◽  
Mice Model ◽  
Alcoholic Fatty Liver ◽  
Heparg Cells ◽  
Hepatic Lipotoxicity

Non-alcoholic fatty liver disease (NAFLD) is the emerging cause of chronic liver disease globally and lack of approved therapies. Here, we investigated the feasibility of combinatorial effects of low molecular weight fucoidan and high stability fucoxanthin (LMF-HSFx) as a therapeutic approach against NAFLD. We evaluated the inhibitory effects of LMF-HSFx or placebo in 42 NAFLD patients for 24 weeks and related mechanism in high fat diet (HFD) mice model and HepaRGTM cell line. We found that LMF-HSFx reduces the relative values of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglyceride, fasting blood glucose and hemoglobin A1c in NAFLD patients. For lipid metabolism, LMF-HSFx reduces the scores of controlled attenuation parameter (CAP) and increases adiponectin and leptin expression. Interestingly, it reduces liver fibrosis in NAFLD patients, either. The proinflammatory cytokines interleukin (IL)-6 and interferon-γ are reduced in LMF-HSFx group. In HFD mice, LMF-HSFx attenuates hepatic lipotoxicity and modulates adipogenesis. Additionally, LMF-HSFx modulates SIRI-PGC-1 pathway in HepaRG cells under palmitic acid-induced lipotoxicity environment. Here, we describe that LMF-HSFx ameliorated hepatic steatosis, inflammation, fibrosis and insulin resistance in NAFLD patients. LMF-HSFx may modulate leptin-adiponectin axis in adipocytes and hepatocytes, then regulate lipid and glycogen metabolism, decrease insulin resistance and is against NAFLD.

scholarly journals P2Y2R Deficiency Ameliorates Hepatic Steatosis by Reducing Lipogenesis and Enhancing Fatty Acid β-Oxidation through AMPK and PGC-1α Induction in High-Fat Diet-Fed Mice

2021 ◽  
Vol 22 (11) ◽  
pp. 5528
Author(s):  
Theodomir Dusabimana ◽  
Eun Jung Park ◽  
Jihyun Je ◽  
Kyuho Jeong ◽  
Seung Pil Yun ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Purinergic Receptor ◽  
Lipolytic Enzyme ◽  
High Fat ◽  
Alcoholic Fatty Liver ◽  
Mitochondrial Fatty Acid

Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease associated with obesity and insulin resistance. Activation of the purinergic receptor P2Y2R has been reported to promote adipogenesis, inflammation and dyslipidemia in adipose tissues in obese mice. However, the role of P2Y2R and its mechanisms in NAFLD remain unknown. We hypothesized that P2Y2R deficiency may play a protective role in NAFLD by modulating lipid metabolism in the liver. In this study, we fed wild type and P2Y2R knockout mice with a high-fat diet (HFD) for 12 weeks and analyzed metabolic phenotypes. First, P2Y2R deficiency effectively improved insulin resistance with a reduction in body weight and plasma insulin. Second, P2Y2R deficiency attenuated hepatic lipid accumulation and injury with reduced alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels. Third, P2Y2R deficiency decreased the expression of fatty acid synthesis mediators (cluster of differentiation (CD36), fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD1)); and increased the expression of adipose triglyceride lipase (ATGL), a lipolytic enzyme. Mechanistically, P2Y2R deficiency increased the AMP-activated protein kinase (AMPK) activity to improve mitochondrial fatty acid β-oxidation (FAO) by regulating acetyl-CoA carboxylase (ACC) and carnitine palmitoyltransferase 1A (CPT1A)-mediated FAO pathway. In addition, P2Y2R deficiency increased peroxisome proliferator-activated gamma co-activator-1α (PGC-1α)-mediated mitochondrial biogenesis. Conclusively, P2Y2R deficiency ameliorated HFD-induced hepatic steatosis by enhancing FAO through AMPK signaling and PGC-1α pathway, suggesting P2Y2R as a promising therapeutic target for NAFLD.

scholarly journals The Severity of Non-Alcoholic Fatty Liver in Type II Diabetes

2018 ◽  
Vol 15 (6) ◽  
pp. 37-42
Author(s):  
Ovidiu Paul Calapod ◽  
Andreea Maria Marin ◽  
Laura Carina Tribus ◽  
Carmen Fierbinţeanu-Braticevici
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Type Ii Diabetes ◽  
Type Ii Diabetes Mellitus ◽  
Diabetic Patients ◽  
Type Ii ◽  
Alcoholic Fatty Liver

AbstractNonalcoholic fatty liver disease (NAFLD) is a chronic liver disease that affects up to one third of the adult population of industrialized countries. The pathophysiological spectrum includes the following entities that are clinically and histologically distinct: hepatic steatosis and steatohepatitis; their subsequent evolution can lead to cirrhosis and hepatocellular carcinoma.The increase of the prevalence of NAFLD during the last decade is caused by the epidemiological and pathophysiological association with type II diabetes and obesity, NAFLD being present in about 70-80% of patients with type II diabetes mellitus. It has long been thought that the relationship between type II diabetes mellitus and NAFLD is unidirectional, fatty liver being secondary to insulin resistance and type II diabetes mellitus, but recent studies show that hepatic steatosis may precede insulin resistance and diabetes mellitus, thus demonstrating abidirectional causal relationship between these two disorders. Weight loss through diet andexercise is effective in preventing and treating NAFLD in diabetic patients; also, drugs that causeweight loss need to be evaluated. Both anti-diabetic medication and statins play an important vrole in the prevention and treatment of NAFLD.

scholarly journals Understanding lipotoxicity in NAFLD pathogenesis: is CD36 a key driver?

2020 ◽  
Vol 11 (9) ◽  
Author(s):  
Patricia Rada ◽  
Águeda González-Rodríguez ◽  
Carmelo García-Monzón ◽  
Ángela M. Valverde
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
Molecular Mechanisms ◽  
Histological Grade ◽  
Soluble Form ◽  
Alcoholic Fatty Liver ◽  
Fatty Acid Translocase ◽  
Promising Therapeutic Approach ◽  
Hepatic Lipotoxicity

Abstract Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease worldwide. NAFLD stages range from simple steatosis (NAFL) to non-alcoholic steatohepatitis (NASH) which can progress to cirrhosis and hepatocellular carcinoma. One of the crucial events clearly involved in NAFLD progression is the lipotoxicity resulting from an excessive fatty acid (FFA) influx to hepatocytes. Hepatic lipotoxicity occurs when the capacity of the hepatocyte to manage and export FFAs as triglycerides (TGs) is overwhelmed. This review provides succinct insights into the molecular mechanisms responsible for lipotoxicity in NAFLD, including ER and oxidative stress, autophagy, lipoapotosis and inflammation. In addition, we highlight the role of CD36/FAT fatty acid translocase in NAFLD pathogenesis. Up-to-date, it is well known that CD36 increases FFA uptake and, in the liver, it drives hepatosteatosis onset and might contribute to its progression to NASH. Clinical studies have reinforced the significance of CD36 by showing increased content in the liver of NAFLD patients. Interestingly, circulating levels of a soluble form of CD36 (sCD36) are abnormally elevated in NAFLD patients and positively correlate with the histological grade of hepatic steatosis. In fact, the induction of CD36 translocation to the plasma membrane of the hepatocytes may be a determining factor in the physiopathology of hepatic steatosis in NAFLD patients. Given all these data, targeting the fatty acid translocase CD36 or some of its functional regulators may be a promising therapeutic approach for the prevention and treatment of NAFLD.

Vitamin D and non-alcoholic fatty liver disease in children

2021 ◽  
Vol 75 (4) ◽  
pp. 335-343
Author(s):  
Terezia Kráľová ◽  
Marek Pršo ◽  
Daniel Čierny ◽  
Zuzana Michnová ◽  
Zuzana Havlíčeková ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Vitamin D ◽  
Liver Disease ◽  
Fatty Liver ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Hypovitaminosis D ◽  
Anthropometric Parameters ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Fatty Liver Disease

Background: Insulin resistance (IR) plays a key role in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Hypovitaminosis D is associated with several diseases, including hepatic steatosis and obesity. Vitamin D (VD) affects insulin secretion and improves tissue sensitivity to insulin, suggesting that hypovitaminosis D is also associated with IR. The leptin-to-adiponectin ratio (LAR) was investigated as a new marker of IR. Aim: The aim of our study was to determine the association between the VD status, NAFLD and IR in paediatric overweight or obese patients. Methods: The study ran from January 2018 to August 2020 and included 100 subjects. We measured their anthropometric parameters, determined their basic laboratory parameters and the level of leptin and adiponectin, calculated BMI, WHR, WHtR, LAR and HOMA-IR. We measured the degree of hepatic steatosis by obtaining the hepatorenal index (HRI) using ultrasonography, and used real-time elastography to determine the elasticity of the liver parenchyma (LFI). Subsequently, we compared the groups of patients with and without hepatic steatosis and looked for correlations in relation to the level of VD and IR. Results: 4.4% of patients had a severe VD deficiency, 55% of the children had hypovitaminosis D, 28.6% had VD insufficiency and 12% of patients had sufficient VD levels. Patients with significant hepatic steatosis (HRI 1.5 and more) had the lowest level of VD (16.61 ±5.62 μg/l, P = 0.015). The level of VD in patients with hepatic steatosis was inversely correlated with waist circumference, hip circumference, height, weight, triacylglycerols, GMT, C-peptide, insulin, HOMA-IR, HRI and LFI. Leptin levels were highest in patients with hepatic pre-steatosis. LAR was highest in the group with hepatic steatosis, but we did not observe significant correlations in relation to other parameters. Conclusion: VD levels are inversely associated with the degree of hepatic steatosis in overweight or obese paediatric patients. HOMA-IR inversely correlates with VD levels and positively with LFI. The LAR value was highest in the group of patients with steatosis, although we did not find out any significant correlations in relation to VD status and HRI. Key words: vitamin D – non-alcoholic fatty liver disease – insulin resistance – leptin – adiponectin – obesity – childhood

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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