Metabolic Syndrome and NASH
Section snippets
Non-alcoholic fatty liver disease/non-alcoholic stereohepatitis and the metabolic syndrome
The abstract of the pioneering study of Ludwig and colleagues [1], first describing non-alcoholic fatty liver disease (NAFLD) in 1980, reads, “Most patients were moderately obese, and many had obesity-associated diseases, such as diabetes mellitus.… ” Only a few years later, Reaven [2] described syndrome X as the association of hyperinsulinemia, hyperglycemia, hyperlipidemia, and hypertension, conditions observed frequently in NAFLD and having insulin resistance as their common pathogenic
Current concepts on metabolic syndrome
When Alberti and Zimmet [5], on behalf of a World Health Organization (WHO) committee of experts, proposed the name, metabolic syndrome, for a condition characterized by multiple metabolic abnormalities, they covered a long-debated area. Unfortunately, their provisional classification did not settle the debate, and in the following years there was a surfeit of articles dealing with the pros and cons of this definition. Several international associations and societies have taken sides and
Non-alcoholic fatty liver disease/non-alchoholic steatohepatitis, insulin resistance, and the metabolic syndrome
Insulin resistance is regarded as a hallmark and a causal factor of NAFLD, even in the absence of obesity and diabetes mellitus. Increasingly it is recognized that multiple genetic and acquired factors can influence insulin action and postprandial lipid metabolism. Diet and nutrition, in particular the amount and type of carbohydrate and fat intake, are linked to insulin resistance, increased risk for developing type 2 diabetes mellitus, and impaired postprandial lipid metabolism [22], thus
Obesity
As discussed previously, obesity is associated strongly with NAFLD. The prevalence of NAFLD is as high as 75% in obese persons who are obese, where truncal obesity becomes a risk factor even in patients who have normal BMI. Hepatic steatosis is documented in individuals who are only 10% above ideal body weight, but a few individuals who are morbidly obese do not have NAFLD. This suggests that obesity and NAFLD are consequences of a common underlying disorder (eg, insulin resistance) or that
Implications for treatment
Given the pathophysiologic association of NASH with insulin resistance and the MS, treatment strategies for metabolic liver disease should aim to improve insulin sensitivity and modify the metabolic risk factors or protect the liver from oxidative stress and further insults. Changes in lifestyle remain the baseline approach, and structured weight-reducing programs, based on diet and physical activity, are recommended by international agencies for all components of MS (Fig. 2). NAFLD of any
Summary
The prevalence of MS is expected to increase systematically in the next decades, because of the rising prevalence of obesity and type 2 diabetes mellitus. The prevalence of NAFLD also is expected to increase, and the presence of multiple metabolic disorders is associated with rates of fibrosis progression, NASH, and, finally, cryptogenic cirrhosis or HCC [69].
In the high number of cases potentially progressing to terminal liver failure, the cardiovascular risk associated with insulin resistance
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m<sup>6</sup>A mRNA methylation-directed myeloid cell activation controls progression of NAFLD and obesity
2021, Cell ReportsCitation Excerpt :These results demonstrated that METTL3 ablation in LysM+ cells affects general myeloid and T cell homeostasis in age. Macrophages are known to play critical roles in obesity and metabolic syndrome that result in a sequence of pathological changes in the liver including steatosis, hepatocyte death, inflammation, and fibrogenesis (Marchesini and Marzocchi, 2007). Consistent with the reduced myeloid cell populations in spleen, PLNs, and liver tissue, aged KO mice developed fewer NAFLD/NASH features compared with WT mice as judged by decreased levels of immune cells infiltrations in liver tissue by the staining of H&E-, CD11b-, and Gr1-positive cells (Figure 1C).
Molecular and Pathological Events Involved in the Pathogenesis of Diabetes-Associated Nonalcoholic Fatty Liver Disease
2019, Journal of Clinical and Experimental HepatologyEndpoints in NASH Clinical Trials: Are We Blind in One Eye?
2024, Metabolites
This work was supported by funds from University of Bologna, Ricerca Fondamentale Orientata, Bologna, 2004.