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Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review.

ABSTRACT: Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an improvement in IR, MS, and both clinical and histologic liver picture. NAFLD and IR are bidirectionally correlated and, consequently, the development of pre-diabetes and diabetes is the most direct consequence at the extrahepatic level. In turn, type 2 diabetes is a well-known risk factor for multiorgan damage, including an involvement of cardiovascular system, kidney and peripheral nervous system. The increased MS incidence worldwide, above all due to changes in diet and lifestyle, is associated with an equally significant increase in NAFLD, with a subsequent rise in both morbidity and mortality due to both metabolic, hepatic and cardiovascular diseases. Therefore, the slowdown in the increase of the "bad company" constituted by MS and NAFLD, with all the consequent direct and indirect costs, represents one of the main challenges for the National Health Systems.

SUBMITTER: Rinaldi L

PROVIDER: S-EPMC7916383 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review.

Rinaldi Luca L Pafundi Pia Clara PC Galiero Raffaele R Caturano Alfredo A Morone Maria Vittoria MV Silvestri Chiara C Giordano Mauro M Salvatore Teresa T Sasso Ferdinando Carlo FC

Antioxidants (Basel, Switzerland) 20210210 2

Non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) are two different entities sharing common clinical and physio-pathological features, with insulin resistance (IR) as the most relevant. Large evidence leads to consider it as a risk factor for cardiovascular disease, regardless of age, sex, smoking habit, cholesterolemia, and other elements of MS. Therapeutic strategies remain still unclear, but lifestyle modifications (diet, physical exercise, and weight loss) determine an im ...[more]

PMID: 33578702

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Project description:BackgroundHigh ultra-processed food (UPF) consumption is associated with the development of various diet-related non-communicable diseases, especially obesity and type 2 diabetes. The present study aimed to systematically review the association between UPF consumption and non-alcoholic fatty liver disease (NAFLD) and its leading risk factors; metabolic syndrome (MetS) and insulin resistance (IR).MethodsA comprehensive search was conducted in PubMed, Scopus, Embase, Web of Science, CINAHL, and Cochrane (March 2023), and references of the identified articles were checked. The search keywords were defined through an exploratory investigation in addition to MeSH and similarly controlled vocabulary thesauruses. Observational and interventional studies were included. Studies that focused only on specific groups of processed foods or overlapping dietary patterns were excluded. The quality assessment was conducted using the Joanna Briggs Institute's critical appraisal tools for observational studies and Cochrane's risk of bias 2 tool for randomized-control trials. A narrative synthesis was employed to report the results.ResultsFifteen studies were included, with a total of 52,885 participants, one randomized-controlled trial, and fourteen observational studies (nine cross-sectional and five prospective). The review has shown a significant association between UPF consumption and NAFLD in three studies out of six, MetS in five out of eight, and IR in one out of three. All large-scale prospective cohorts that studied NAFLD or MetS outcomes demonstrated a positive association. In contrast, studies that did not demonstrate significant associations were mostly cross-sectional and small. The evidence for an association with IR was insufficient and conflicting.ConclusionThe included studies are few, observational, and based upon self-reported dietary assessment tools. However, current evidence indicates that UPF is not only associated with obesity and type 2 diabetes but may also be a risk factor for NAFLD and MetS. UPF is a worldwide concern deserving further longitudinal research.Impact and implicationsOverconsumption of ultra-processed food (UPF) may lead to the development of obesity and type 2 diabetes, but the association with non-alcoholic fatty liver disease (NAFLD) is not well established. The present systematic review shows that UPF may be associated with NAFLD, although more large prospective studies are needed. These findings emphasize the importance of minimizing the consumption of UPF to prevent NAFLD and other metabolic diseases among the general adult population. This systematic review and further prospective studies, epidemiological or interventional, can help physicians provide patients with evidence-based nutritional recommendations and will support policymakers in restricting the marketing of UPF as well as promoting affordable, healthy, and minimally processed foods.

Project description:ObjectiveMetabolic syndrome (MetS) and non-alcoholic fatty liver disease (NAFLD) are the leading chronic diseases worldwide. There are still many controversies about the association between serum bilirubin and MetS or NAFLD. This study aims to evaluate the association of serum total bilirubin (TBIL), direct bilirubin (DBIL), indirect bilirubin (IBIL) with MetS and NAFLD.MethodsMultiple databases were searched for relevant studies until November 2021. Randomized controlled trials, cross-sectional and cohort studies evaluating the association between serum bilirubin levels and MetS or NAFLD were included.ResultsTwenty-four cross-sectional and cohort studies with 101, 517 participants were finally analyzed. Fifteen studies and 6 studies evaluated the association between bilirubin and MetS or NAFLD in health screening population, respectively, while 3 studies evaluated the association between bilirubin and non-alcoholic steatohepatitis (NASH) in NAFLD patients. Random effect model analysis showed the inverse association between TBIL and MetS in male (95%CI=0.71-0.96) and gender-neutral (95%CI=0.61-0.91) group. However, no significant association was found in females. Notably, the inverse association between DBIL and MetS was noticed in male (95%CI=0.36-0.75), female (95%CI=0.16-0.58) and gender-neutral population (95%CI=0.67-0.92). IBIL level was inversely associated with MetS in females (95%CI=0.52-0.96), whereas no statistical correlation presented in males. TBIL was not statistically correlated with NAFLD in gender-neutral or male subgroup. Similarly, there were no association between DBIL or IBIL and NAFLD in gender-neutral subgroup. However, the negative correlation between DBIL and NAFLD existed in males (95%CI=0.76-0.96). In NAFLD patients, IBIL analysis showed an inverse association with NASH (95%CI=0.01-0.12).ConclusionSerum TBIL and DBIL levels, especially DBIL levels, assume an inverse correlation with MetS in healthy population. Serum IBIL is inversely associated with the onset and degree of NASH in NAFLD patients. Exogenous bilirubin supplement may be a potential strategy to assist in lowering the risk of developing MetS and NAFLD.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021293349.

Dataset Information

Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review.

Publications

Mechanisms of Non-Alcoholic Fatty Liver Disease in the Metabolic Syndrome. A Narrative Review.

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