NAFLD

Gut microbiota is involved in obesity, metabolic syndrome and the progression of nonalcoholic fatty liver disease (NAFLD). It has been recently suggested that the flavonoid quercetin may have the ability to modulate the intestinal microbiota composition, suggesting a prebiotic capacity which highlights a great therapeutic potential in NAFLD. The present study aims to investigate benefits of experimental treatment with quercetin on gut microbial balance and related gut-liver axis activation in a nutritional animal model of NAFLD associated to obesity. C57BL/6J mice were challenged with high fat diet (HFD) supplemented or not with quercetin for 16 weeks. HFD induced obesity, metabolic syndrome and the development of hepatic steatosis as main hepatic histological finding. Increased accumulation of intrahepatic lipids was associated with altered gene expression related to lipid metabolism, as a result of deregulation of their major modulators. Quercetin supplementation decreased insulin resistance and NAFLD activity score, by reducing the intrahepatic lipid accumulation through its ability to modulate lipid metabolism gene expression, cytochrome P450 2E1 (CYP2E1)-dependent lipoperoxidation and related lipotoxicity. Microbiota composition was determined via 16S ribosomal RNA Illumina next-generation sequencing. Metagenomic studies revealed HFD-dependent differences at phylum, class and genus levels leading to dysbiosis, characterized by an increase in Firmicutes/Bacteroidetes ratio and in Gram-negative bacteria, and a dramatically increased detection of Helicobacter genus. Dysbiosis was accompanied by endotoxemia, intestinal barrier dysfunction and gut-liver axis alteration and subsequent inflammatory gene overexpression. Dysbiosis-mediated toll-like receptor 4 (TLR-4)-NF-κB signaling pathway activation was associated with inflammasome initiation response and reticulum stress pathway induction. Quercetin reverted gut microbiota imbalance and related endotoxemia-mediated TLR-4 pathway induction, with subsequent inhibition of inflammasome response and reticulum stress pathway activation, leading to the blockage of lipid

Nutritional diets are essential to prevent nonalcoholic fatty liver disease (NAFLD) in the global obesity and diabetes epidemic. The ingestion of palmitic acid-rich diets induces NAFLD in animal and human studies. The beneficial properties of olive oil (oleic acid) may be superseded by ingestion of palmitic acid-rich diets. Hepatic caffeine metabolism is regulated by palmitic and oleic acid with effects of these fats on amyloid beta metabolism. Healthy fats such as olive oil may facilitate rapid amyloid beta clearance in the periphery to maintain drug therapy in diabetes and various neurological diseases. Repression of the anti-aging gene sirtuin 1 (Sirt 1) prevents the beneficial properties of olive oil. Brain disorders induce NAFLD and supersede caffeine's therapeutic effects in the prevention of NAFLD. Delayed hepatic caffeine metabolism in NAFLD and increased caffeine transport to the brain with aging-induced mitophagy in neurons with induction of type 3 diabetes and neurodegenerative disease.

Non-alcoholic fatty liver disease (NAFLD) is now the most common cause of liver disease worldwide, and represents an increasingly important cause of hepatocellular carcinoma (HCC). As the prevalence of NAFLD has increased, the burden of NAFLD-related HCC has been rising in parallel. This is particularly evident in Western countries, where NAFLD is estimated to account for 10%-59% of all HCC. NAFLD-related HCC can occur in the presence or absence of cirrhosis, and, while those with cirrhosis remain at the greatest risk, factors such as steatohepatitis, age, genetic polymorphisms, type 2 diabetes mellitus and obesity also appear have an impact on the risk of developing HCC in NAFLD. In this review, we present the epidemiology of NAFLD-related HCC from a Western perspective, highlighting gaps in current knowledge and future directions for research in this field.

Despite the fact that non-alcoholic fatty liver disease (NAFLD) and its severe clinical forms [non-alcoholic steatohepatitis (NASH) and NASH-cirrhosis] are highly prevalent in the general population, there are no licensed drugs for NAFLD, and lifestyle intervention remains the only treatment accepted by international guidelines. This is despite massive investments in research by pharmaceutical companies. In the presence of type 2 diabetes, novel anti-diabetic drugs offer an opportunity to reduce the burden of NAFLD, by adequate control of glucose and lipid metabolism, also reducing the risk of NASH progression, advanced fibrosis, and finally hepatocellular carcinoma. We extensively reviewed the literature, based either on registration studies, ad hoc randomized studies or real-world data, to define the effectiveness of anti-diabetic drugs in the treatment of NAFLD and prevention of hepatocellular carcinoma (HCC). Metformin provides the best evidence for decreased risk of HCC, piogli...

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition worldwide due to the global proliferation of obesity, which has become an insidious healthcare epidemic. While nonalcoholic fatty liver is recognized as a multi-system disease, benign and pernicious in its unfolding, nonalcoholic steatohepatitis is the more severe form progressing from cirrhosis to hepatocellular carcinoma. Unfortunately, liver biopsy-beset by many limitations-is the only accurate diagnostic tool setting the benchmark for a plethora of non-invasive biomarkers which have so far proved limited in their reliability and take-up. As a result, we need better diagnostic and prognostic tools to aid in the identification and stratification of patients at risk of disease progression in order to enhance treatment and monitoring strategies. In this review, we explore the performance as well as pros and cons of three novel technologies that could have the potential to become the next generation in NAFLD diagnostic testing. To harness these technologies, however, we suggest that more work needs to be done to refine and validate the technology features under review, while suggesting ways in which personalized medicine could be mobilized to discover the next generation in non-invasive diagnostics.

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis and staging. Methods: A systematic literature search was conducted on any relevant database or institutional website to find guidelines on NAFLD assessment intended for clinical use on humans, in English, published from January 2010 to August 2020. Included guidelines were appraised using the AGREE II Instrument; those with higher scores and intended for use in adult patients were included in a comparative analysis. Results: Fourteen guidelines were included in the systematic review, eight of which reached an AGREE II score sufficiently high to be recommended for clinical use, of which one developed for pediatric patients only. British and North American guidelines received the highest scores. Most guidelines recommend a screening or case-finding approach in patients with metabolic risk factors who are at increased risk of stea...

The diabetes epidemic is now expected by the year 2050 to become a global pandemic with approx. 592 million affected in both the developed and developing world. The treatment of diabetes by insulin therapy has been the focus for many diabetics with the improvement and prevention of various diseases such as cardio-vascular disease, kidney disease and neurodegeneration. The global nonalcoholic fatty liver disease (NAFLD) epidemic has now become of major concern to diabetes with critical interest in insulin therapy to reverse and stabilize autoimmune disease with relevance to NAFLD and the diabetes pandemic. Dietary components that activate anti-aging genes improve insulin therapy and should be assessed with specific amounts and doses of Indian spices consumed that may not interfere with insulin therapy and induce mitophagy in various diseases. Food quality, appetite control and core body temperature are critical to maintain insulin therapy with unhealthy diets linked to NAFLD and diabetes. Genomic medicine and dietary activators are essential to maintain insulin therapy and prevent toxic immune reactions with relevance to NAFLD and diabetes management.

Abstract: Nonalcoholic fatty liver disease (NAFLD) affects about 30 % of the general population in the United States and includes a spectrum of disease that includes simple steatosis, non-alcoholic steatohepatitis (NASH), fibrosis and cirrhosis. Significant insight has been gained into our understanding of the pathogenesis of NALFD; however the key metabolic aberrations underlying lipid accumulation in hepatocytes and the progression of NAFLD remain to be elucidated. Accumulating and emerging evidence indicate that hepatic mitochondria play a critical role in the development and pathogenesis of steatosis and NAFLD. Here, we review studies that document a link between the pathogenesis of NAFLD and hepatic mitochondrial dysfunction with particular focus on new insights into the role of impaired fatty acid oxidation, the transcription factor peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), and sirtuins in development and progression of NAFLD.

Non-alcoholic fatty liver disease represents the most common liver disease and is characterized by an excess of lipid accumulation in hepatocytes, mainly stored as triglycerides. Phaeodactylum tricornutum is a marine microalga, which is rich in bioactive molecules known to be hepatoprotective, such as n-3 long-chain polyunsaturated fatty acids and fucoxanthin. The aim of this study was to investigate the effects of a carotenoid extract from P. tricornutum in a cellular model of non-alcoholic fatty liver disease induced by palmitate treatment. The combined effects of carotenoids and lipids, especially n-3 long-chain polyunsaturated fatty acids, were also investigated by using a total lipophilic extract. HepG2 cells were exposed for 24 h to 250 µM palmitate with or without the addition of carotenoid extract (6 μg/mL) or total lipophilic extract (100 μg/mL). The addition of carotenoid extract or total lipophilic extract prevented the accumulation of triglycerides, total cholesterol and...

The use of the products derived from the olive tree on human health dates back centuries. In several civilizations, the olive tree had and still has a very strong cultural and religious symbolism. Notably, the official seal and emblem of the World Health Organization features the rod of Asclepius over a world map surrounded by olive tree branches, chosen as a symbol of peace and health. Recently, accumulating experimental, clinical and epidemiological data have provided support to the traditional beliefs of the beneficial effect provided by olive derivates. In particular, the polyphenols present in olive leaves, olives, virgin (unrefined) olive oil and olive mill waste are potent antioxidant and radical scavengers with anti-tumor and anti-inflammatory properties. Here, we review the positive impact on human health of oleuropein, the most prevalent polyphenol present in olives. In addition, we provide data collected in our laboratory on the role of oleuropein in counteracting lipid accumulation in a mouse model of non-alcoholic fatty liver disease.

Background: Timely diagnosis of liver cirrhosis is vital for preventing further liver damage and giving the patient the chance of transplantation. Although biopsy of the liver is the gold standard for cirrhosis assessment, it has some risks and limitations and this has led to the development of new noninvasive methods to determine the stage and prognosis of the patients. We aimed to design an artificial neural network (ANN) model to diagnose cirrhosis patients with non-alcoholic fatty liver disease (NAFLD) using routine laboratory data. Methods: Data were collected from 392 patients with NAFLD by the Middle East Research Center in Tehran. Demographic variables, history of diabetes, INR, complete blood count, albumin, ALT, AST and other routine laboratory tests, examinations and medical history were gathered. Relevant variables were selected by means of feature extraction algorithm (Knime software) and were accredited by the experts. A neural network was developed using the MATLAB so...

Aim: In this systematic review, guidelines on non-alcoholic fatty liver disease (NAFLD) were evaluated, aiming at a guideline synthesis focusing on diagnosis and staging. Methods: A systematic literature search was conducted on any relevant database or institutional website to find guidelines on NAFLD assessment intended for clinical use on humans, in English, published from January 2010 to August 2020. Included guidelines were appraised using the AGREE II Instrument; those with higher scores and intended for use in adult patients were included in a comparative analysis. Results: Fourteen guidelines were included in the systematic review, eight of which reached an AGREE II score sufficiently high to be recommended for clinical use, of which one developed for pediatric patients only. British and North American guidelines received the highest scores. Most guidelines recommend a screening or case-finding approach in patients with metabolic risk factors who are at increased risk of stea...

The use of the products derived from the olive tree on human health dates back centuries. In several civilizations, the olive tree had and still has a very strong cultural and religious symbolism. Notably, the official seal and emblem of the World Health Organization features the rod of Asclepius over a world map surrounded by olive tree branches, chosen as a symbol of peace and health. Recently, accumulating experimental, clinical and epidemiological data have provided support to the traditional beliefs of the beneficial effect provided by olive derivates. In particular, the polyphenols present in olive leaves, olives, virgin (unrefined) olive oil and olive mill waste are potent antioxidant and radical scavengers with anti-tumor and anti-inflammatory properties. Here, we review the positive impact on human health of oleuropein, the most prevalent polyphenol present in olives. In addition, we provide data collected in our laboratory on the role of oleuropein in counteracting lipid a...

The epidemiology of nonalcoholic fatty liver disease goes hand-in-hand with the obesity pandemic. The pathogenesis of fatty liver has shifted from an hepatocentric view to an adipocentric view, in which the overloaded adipose tissue spills out lipids that spread to ectopic tissues and organs such as the liver, elicits inflammation, and changes its adipokines profile promoting insulin resistance and the metabolic syndrome. Up to 40% of nonalcoholic fatty liver disease (NAFLD) patients are not obese and up to 20% are actually lean. Furthermore roughly 10% of lean subjects have NAFLD. In fact, adiposopathy can occur in patients with normal weight, and it is associated with expansion of metabolically active visceral fat and a qualitatively different adipose tissue that becomes overwhelmed after challenged by a mildly positive energy balance. This defines the concept of personal fat threshold that when exceeded results in metabolic dysfunction. Overweight/obese persons have higher probability of exceeding that threshold, explaining why adiposopathy/metabolic syndrome/NAFLD is more frequent in the obese. In this article, the epidemiology, pathogenesis, and management of patients with lean NAFLD are reviewed with an emphasis on reconciling the concepts of NAFLD in its relationship with adiposity and of NAFLD in lean individuals.

Dyslipidemia is one of the key risk factors for cardiovascular disease with relevance to non alcoholic fatty liver disease (NAFLD) and diabetes. The management of dyslipidemia in diabetes continues to remain controversial and improvements in the characteristic diabetic dyslipidemia of high triglyceride and low HDL may now indicate that defective mitochondrial biogenesis is underway early in life. Diabetes and defective mitochondrial function induce delayed postprandial lipid metabolism that is involved in diabetic dyslipidemia. The clinical management of diabetes in the young and elderly now involves the heat shock gene Sirtuin 1 (Sirt 1) involved with careful core body temperature regulation and maintainance of liver and brain mitochondrial energy metabolism. Consumption of Sirt 1 inhibitors such as alcohol, suramin and palmitic acid should be avoided to prevent cell mitochondrial apoptosis and to stabilize NAFLD with relevance to hyperglycemia induced oxidative stress and myocardial infarction.

Insulin resistance is associated with ectopic lipid accumulation. Physical activity improves insulin sensitivity, but the impact of exercise on lipid handling in insulin-resistant tissues remains to be elucidated. The present study characterizes the effects of acute exercise on lipid content and dietary lipid partitioning in liver and skeletal muscle of lean and diabetic rats by use of magnetic resonance spectroscopy (MRS). After baseline measurements, rats were randomized to exercise or no-exercise groups. A subset of animals was subjected to MRS directly after 1 h of treadmill running for measurement of total intrahepatocellular lipid (IHCL) and intramyocellular lipid (IMCL) content (n 7 lean and diabetic rats). The other animals were administered 13 C-labeled lipids orally after treadmill visit (with or without exercise) followed by MRS measurements after 4 and 24 h to determine the 13 C enrichment of IHCL and IMCL (n 8 per group). Total IHCL and IMCL content were fivefold higher in diabetic vs. lean rats (P 0.001). Exercise did not significantly affect IHCL content but reduced IMCL by 25 7 and 33 4% in lean and diabetic rats (P 0.05), respectively. Uptake of dietary lipids in liver and muscle was 2.3-fold greater in diabetic vs. lean rats (P 0.05). Prior exercise did not significantly modulate dietary lipid uptake into muscle, but in liver of both lean and diabetic rats, lipid uptake was 44% reduced after acute exercise (P 0.05). In conclusion, IMCL but not IHCL represents a viable substrate source during exercise in both lean and diabetic rats, and exercise differentially affects dietary lipid uptake in muscle and liver.