scholarly journals Metabolomic Salivary Signature of Pediatric Obesity Related Liver Disease and Metabolic Syndrome

Nutrients ◽  
2019 ◽  
Vol 11 (2) ◽  
pp. 274 ◽  
Author(s):  
Jacopo Troisi ◽  
Federica Belmonte ◽  
Antonella Bisogno ◽  
Luca Pierri ◽  
Angelo Colucci ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Hepatic Steatosis ◽  
Pediatric Obesity ◽  
Fatty Acid Synthase ◽  
Laboratory Data ◽  
Treatment Strategies ◽  
Normal Weight ◽  
Nonalcoholic Fatty Liver ◽  
Related Liver Disease

Pediatric obesity-related metabolic syndrome (MetS) and nonalcoholic fatty liver disease (NAFLD) are increasingly frequent conditions with a still-elusive diagnosis and low-efficacy treatment and monitoring options. In this study, we investigated the salivary metabolomic signature, which has been uncharacterized to date. In this pilot-nested case-control study over a transversal design, 41 subjects (23 obese patients and 18 normal weight (NW) healthy controls), characterized based on medical history, clinical, anthropometric, and laboratory data, were recruited. Liver involvement, defined according to ultrasonographic liver brightness, allowed for the allocation of the patients into four groups: obese with hepatic steatosis ([St+], n = 15) and without hepatic steatosis ([St–], n = 8), and with (n = 10) and without (n = 13) MetS. A partial least squares discriminant analysis (PLS-DA) model was devised to classify the patients’ classes based on their salivary metabolomic signature. Pediatric obesity and its related liver disease and metabolic syndrome appear to have distinct salivary metabolomic signatures. The difference is notable in metabolites involved in energy, amino and organic acid metabolism, as well as in intestinal bacteria metabolism, possibly reflecting diet, fatty acid synthase pathways, and the strict interaction between microbiota and intestinal mucins. This information expands the current understanding of NAFLD pathogenesis, potentially translating into better targeted monitoring and/or treatment strategies in the future.

Does Nonalcoholic Fatty Liver Disease Predispose Patients to Hepatocellular Carcinoma in the Absence of Cirrhosis?

2008 ◽  
Vol 132 (11) ◽  
pp. 1761-1766 ◽  
Author(s):  
Grace Guzman ◽  
Elizabeth M. Brunt ◽  
Lydia M. Petrovic ◽  
Gregorio Chejfec ◽  
Thomas J. Layden ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Laboratory Data ◽  
Key Words Hepatocellular Carcinoma ◽  
Nonalcoholic Fatty Liver ◽  
The Metabolic Syndrome

Abstract Context.—Hepatocellular carcinoma (HCC) is recognized as a complication of cirrhosis related to nonalcoholic fatty liver disease (NAFLD). Diabetes and the metabolic syndrome are also associated with HCC. However, it is not clear whether NAFLD predisposes patients to HCC in the absence of cirrhosis. Objective.—To seek evidence that HCC can develop in NAFLD unaccompanied by cirrhosis. Design.—Retrospective case study was performed on cases from 2004 to 2007 at the University of Illinois at Chicago Medical Center, using the key words hepatocellular carcinoma, liver explant, and liver resection. The diagnosis of HCC was identified and confirmed by hematoxylin-eosin–stained slides in 50 cases. Cause of liver disease was determined by review of liver histology, clinical history, and laboratory data. Results.—Three patients presented with advanced HCC with features of metabolic syndrome, including an elevated body mass index. Each patient had bland steatosis on liver biopsy, without fibrosis or cirrhosis. None of the 3 patients had evidence of any cause for liver disease other than NAFLD. Conclusions.—The cases presented here suggest that NAFLD may predispose patients to HCC in the absence of cirrhosis. Further studies are needed to confirm this potentially important observation.

Therapeutic role of niacin in the prevention and regression of hepatic steatosis in rat model of nonalcoholic fatty liver disease

2014 ◽  
Vol 306 (4) ◽  
pp. G320-G327 ◽  
Author(s):  
Shobha H. Ganji ◽  
Gary D. Kukes ◽  
Nils Lambrecht ◽  
Moti L. Kashyap ◽  
Vaijinath S. Kamanna
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Liver Fat ◽  
Mrna Levels ◽  
Nonalcoholic Fatty Liver

Nonalcoholic fatty liver disease (NAFLD), a leading cause of liver damage, comprises a spectrum of liver abnormalities including the early fat deposition in the liver (hepatic steatosis) and advanced nonalcoholic steatohepatitis. Niacin decreases plasma triglycerides, but its effect on hepatic steatosis is elusive. To examine the effect of niacin on steatosis, rats were fed either a rodent normal chow, chow containing high fat (HF), or HF containing 0.5% or 1.0% niacin in the diet for 4 wk. For regression studies, rats were first fed the HF diet for 6 wk to induce hepatic steatosis and were then treated with niacin (0.5% in the diet) while on the HF diet for 6 wk. The findings indicated that inclusion of niacin at 0.5% and 1.0% doses in the HF diet significantly decreased liver fat content, liver weight, hepatic oxidative products, and prevented hepatic steatosis. Niacin treatment to rats with preexisting hepatic steatosis induced by the HF diet significantly regressed steatosis. Niacin had no effect on the mRNA expression of fatty acid synthesis or oxidation genes (including sterol-regulatory element-binding protein 1, acetyl-CoA carboxylase 1, fatty acid synthase, and carnitine palmitoyltransferase 1) but significantly inhibited mRNA levels, protein expression, and activity of diacylglycerol acyltrasferase 2, a key enzyme in triglyceride synthesis. These novel findings suggest that niacin effectively prevents and causes the regression of experimental hepatic steatosis. Approved niacin formulation(s) for other indications or niacin analogs may offer a very cost-effective opportunity for the clinical development of niacin for treating NAFLD and fatty liver disease.

scholarly journals Abnormal Metabolism in the Progression of Nonalcoholic Fatty Liver Disease to Hepatocellular Carcinoma: Mechanistic Insights to Chemoprevention

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3473
Author(s):  
Danny Orabi ◽  
Nathan Berger ◽  
J. Brown
Keyword(s):  
Hepatocellular Carcinoma ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Treatment Strategies ◽  
Farnesoid X Receptor ◽  
Nonalcoholic Fatty Liver ◽  
Prevention And Treatment

Nonalcoholic fatty liver disease (NAFLD) is on the rise and becoming a major contributor to the development of hepatocellular carcinoma (HCC). Reasons for this include the rise in obesity and metabolic syndrome in contrast to the marked advances in prevention and treatment strategies of viral HCC. These shifts are expected to rapidly propel this trend even further in the coming decades, with NAFLD on course to become the leading etiology of end-stage liver disease and HCC. No Food and Drug Administration (FDA)-approved medications are currently available for the treatment of NAFLD, and advances are desperately needed. Numerous medications with varying mechanisms of action targeting liver steatosis and fibrosis are being investigated including peroxisome proliferator-activated receptor (PPAR) agonists and farnesoid X receptor (FXR) agonists. Additionally, drugs targeting components of metabolic syndrome, such as antihyperglycemics, have been found to affect NAFLD progression and are now being considered in the treatment of these patients. As NAFLD drug discovery continues, special attention should be given to their relationship to HCC. Several mechanisms in the pathogenesis of NAFLD have been implicated in hepatocarcinogenesis, and therapies aimed at NAFLD may additionally harbor independent antitumorigenic potential. This approach may provide novel prevention and treatment strategies.

scholarly journals Gender Differences in the Relationships among Metabolic Syndrome and Various Obesity-Related Indices with Nonalcoholic Fatty Liver Disease in a Taiwanese Population

2021 ◽  
Vol 18 (3) ◽  
pp. 857
Author(s):  
I-Ting Lin ◽  
Mei-Yueh Lee ◽  
Chih-Wen Wang ◽  
Da-Wei Wu ◽  
Szu-Chia Chen
Keyword(s):  
Metabolic Syndrome ◽  
Gender Differences ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Tyg Index ◽  
And Gender

The incidence of nonalcoholic fatty liver disease(NAFLD) is increasing worldwide, and it is strongly associated with metabolic syndrome (MetS) and some obesity-related indices. However, few studies have investigated gender differences in these associations. The aim of this study was to investigate associations among MetS and various obesity-related indices with NAFLD, and also look at gender differences in these associations. We enrolled participants who completed a health survey in southern Taiwan. MetS was defined according to the Adult Treatment Panel III for Asians, and the following obesity-related indices were calculated: body mass index (BMI), waist-to-height ratio (WHtR), waist–hip ratio (WHR), lipid accumulation product (LAP), body roundness index (BRI), conicity index (CI), visceral adiposity index (VAI), body adiposity index (BAI), abdominal volume index (AVI), triglyceride-glucose (TyG) index, and hepatic steatosis index (HSI). NAFLD was diagnosed when hepatic steatosis was noted on a liver ultrasound. A total of 1969 (764 men and 1205 women) participants were enrolled. Multivariable analysis showed that both male and female participants with MetS, high BMI, high WHtR, high WHR, high LAP, high BRI, high CI, high VAI, high BAI, high AVI, high TyG index, and high HSI were significantly associated with NAFLD. In addition, the interactions between MetS and gender, WHR and gender, LAP and gender, and TyG index and gender on NAFLD were statistically significant. Among these obesity-related indices, HSI and LAP had the greatest area under the curve in both men and women. Furthermore, stepwise increases in the number of MetS components and the values of indices corresponding to the severity of NAFLD were noted. In conclusion, our results demonstrated significant relationships between MetS and obesity-related indices with NAFLD, and also stepwise increases in the number of MetS components and the values of indices with the severity of NAFLD. MetS, WHR, LAP, and TyG index were associated with NAFLD more obviously in women than in men.

scholarly journals Triglyceride and Glucose Index as a Screening Tool for Nonalcoholic Liver Disease in Patients with Metabolic Syndrome

2021 ◽  
Author(s):  
Anca Maria Amzolini ◽  
Fortofoiu Mircea-Catalin ◽  
Anca Barău Al-Hija ◽  
Ionela Mihaela Vladu ◽  
Diana Clenciu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Screening Tool ◽  
Liver Enzymes ◽  
Mean Value ◽  
Normal Weight ◽  
Nonalcoholic Fatty Liver ◽  
Tyg Index ◽  
Significant Difference ◽  
Nonalcoholic Liver Disease

Background: Nonalcoholic fatty liver disease (NAFLD) is regarded as a component of metabolic syndrome, which has insulin resistance (IR) as the primary physiopathological event. The aim of study was to establish the association between IR, assessed using triglyceride and glucose index (TyG), and histopathological features of NAFLD lesions. Methods: The study included patients with metabolic syndrome. Fasting plasma glucose (FPG), fasting lipid profiles and liver enzymes were measured. IR was assessed by TyG index. Liver biopsy was performed for assessment steatosis and fibrosis. Results: TyG index had a mean value of 8.93 ± 1.45, with a higher value in the patients with overweight (p=0.002) and obesity (p=0.004) than in the patients with normal weight. TyG index mean value of 8.78 ± 0.65 in subjects without NASH, 8.91 ± 0.57 in patients with borderline NASH and 9.13 ± 0.55 in patients with definite NASH. Significant difference was found between subjects without NASH and the ones with definite NASH (p=0.004). The analysis of the area under the ROC curve proved that TyG index is a predictor for NASH (p=0.043). Conclusion: TyG index is a facile tool used to identify individuals at risk for NAFLD, but not for the progression of liver lesions.

scholarly journals FTY720/fingolimod decreases hepatic steatosis and expression of fatty acid synthase in diet-induced nonalcoholic fatty liver disease in mice

2019 ◽  
Vol 60 (7) ◽  
pp. 1311-1322 ◽  
Author(s):  
Timothy D. Rohrbach ◽  
Amon Asgharpour ◽  
Melissa A. Maczis ◽  
David Montefusco ◽  
L. Ashley Cowart ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepatic Steatosis ◽  
Fatty Liver Disease ◽  
Fatty Acid Synthase ◽  
Nonalcoholic Fatty Liver

scholarly journals Triglyceride and Glucose Index as a Screening Tool for Nonalcoholic Liver Disease in Patients with Metabolic Syndrome

2021 ◽  
Author(s):  
Anca Maria Amzolini ◽  
Fortofoiu Mircea-Catalin ◽  
Anca Barău Al-Hija ◽  
Ionela Mihaela Vladu ◽  
Diana Clenciu ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Liver Disease ◽  
Screening Tool ◽  
Liver Enzymes ◽  
Mean Value ◽  
Normal Weight ◽  
Nonalcoholic Fatty Liver ◽  
Tyg Index ◽  
Significant Difference ◽  
Nonalcoholic Liver Disease

Background: Nonalcoholic fatty liver disease (NAFLD) is regarded as a component of metabolic syndrome, which has insulin resistance (IR) as the primary physiopathological event. The aim of study was to establish the association between IR, assessed using triglyceride and glucose index (TyG), and histopathological features of NAFLD lesions. Methods: The study included patients with metabolic syndrome. Fasting plasma glucose (FPG), fasting lipid profiles and liver enzymes were measured. IR was assessed by TyG index. Liver biopsy was performed for assessment steatosis and fibrosis. Results: TyG index had a mean value of 8.93 ± 1.45, with a higher value in the patients with overweight (p=0.002) and obesity (p=0.004) than in the patients with normal weight. TyG index mean value of 8.78 ± 0.65 in subjects without NASH, 8.91 ± 0.57 in patients with borderline NASH and 9.13 ± 0.55 in patients with definite NASH. Significant difference was found between subjects without NASH and the ones with definite NASH (p=0.004). The analysis of the area under the ROC curve proved that TyG index is a predictor for NASH (p=0.043). Conclusion: TyG index is a facile tool used to identify individuals at risk for NAFLD, but not for the progression of liver lesions.

scholarly journals Multidisciplinary Pharmacotherapeutic Options for Nonalcoholic Fatty Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-13 ◽  
Author(s):  
Kei Nakajima
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Fatty Liver Disease ◽  
Lipid Lowering ◽  
Nonalcoholic Fatty Liver ◽  
Ras Blockers

Nonalcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are multidisciplinary liver diseases that often accompany type 2 diabetes or metabolic syndrome, which are characterized by insulin resistance. Therefore, effective treatment of type 2 diabetes and metabolic syndrome should target not only the cardiometabolic abnormalities, but also the associated liver disorders. In the last decade, it has been shown that metformin, thiazolidinediones, vitamin E, ezetimibe, n-3 polyunsaturated fatty acids, renin-angiotensin system (RAS) blockers, and antiobesity drugs may improve hepatic pathophysiological disorders as well as clinical parameters. Accordingly, insulin sensitizers, antioxidative agents, Niemann-Pick C1-like 1 (NPC1L1) inhibitors, RAS blockers, and drugs that target the central nervous system may represent candidate pharmacotherapies for NAFLD and possibly NASH. However, the efficacy, safety, and tolerability of long-term treatment (potentially for many years) with these drugs have not been fully established. Furthermore, clinical trials have not comprehensively examined the efficacy of lipid-lowering drugs (i.e., statins, fibrates, and NPC1L1 inhibitors) for the treatment of NAFLD. Although clinical evidence for RAS blockers and incretin-based agents (GLP-1 analogs and dipeptidyl peptidase-4 inhibitors) is also lacking, these agents are promising in terms of their insulin-sensitizing and anti-inflammatory effects without causing weight gain.

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