Fatty Liver A Novel Component of the Metabolic Syndrome

Department of Medicine, Division of Diabetes, University of Helsinki, Finland, FIN-00029 HUCH, Helsinki, Finland.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 6). 02/2008; 28(1):27-38. DOI: 10.1161/ATVBAHA.107.147538
Source: PubMed


Although the epidemic of obesity has been accompanied by an increase in the prevalence of the metabolic syndrome, not all obese develop the syndrome and even lean individuals can be insulin resistant. Both lean and obese insulin resistant individuals have an excess of fat in the liver which is not attributable to alcohol or other known causes of liver disease, a condition defined as nonalcoholic fatty liver disease (NAFLD) by gastroenterologists. The fatty liver is insulin resistant. Liver fat is highly significantly and linearly correlated with all components of the metabolic syndrome independent of obesity. Overproduction of glucose, VLDL, CRP, and coagulation factors by the fatty liver could contribute to the excess risk of cardiovascular disease associated with the metabolic syndrome and NAFLD. Both of the latter conditions also increase the risk of type 2 diabetes and advanced liver disease. The reason why some deposit fat in the liver whereas others do not is poorly understood. Individuals with a fatty liver are more likely to have excess intraabdominal fat and inflammatory changes in adipose tissue. Intervention studies have shown that liver fat can be decreased by weight loss, PPARgamma agonists, and insulin therapy.

23 Reads
  • Source
    • "For example, they may have the same pathophysiological basis of insulin resistance[23]. A systematic review suggested a potential predictive effect of liver fat on the presence of MS[23]. However, no evidence was provided regarding the causal association between NASH and MS. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The occurrence of metabolic syndrome (MS) represents an independent risk factor for developing cardiovascular disease states in patients suffering from type 2 diabetes mellitus. Moreover, both the size of LDL particles and liver dysfunction identified as non alcoholic steato-hepatitis (NASH) represent important biomarkers for the development of cardiometabolic risk in patients with MS. Recent evidence shows that bergamot polyphenolic fraction (BPF) in patients with MS and NASH induces a significant reduction of fasting plasma glucose, serum LDL cholesterol and triglycerides alongside with an increase of HDL cholesterol. In addition, a significant reduction of both ultrasonographic, TC scans and metabolic biomarkers of NASH as well as a significant reduction of small dense LDL particles were found after BPF treatment suggesting a beneficial effect of bergamot-extract in patients with MS and NASH. This suggests a potential preventive role of bergamot derivatives in reducing cardiometabolic risk.
    Full-text · Article · Nov 2015 · PharmaNutrition
    • "The metabolic syndrome (MetS) manifests as a clustering of risk factors including abdominal obesity, atherogenic dyslipidemia, elevated blood pressure, insulin resistance, and prothrombotic and proinflammatory states [1] [2]. Individuals with MetS have at least a fivefold increased risk of developing type 2 diabetes (T2D), a twofold increased risk of cardiovascular diseases [3], and increased susceptibility to several other disorders including fatty liver disease [4], sleep apnea [5], and some forms of cancer [6]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The metabolic syndrome (MetS) is a constellation of metabolic disorders that increase the risk of developing several diseases including type 2 diabetes and cardiovascular diseases. Although genome-wide association studies (GWAS) have successfully identified variants associated with individual traits comprising MetS, the genetic basis and pathophysiological mechanisms underlying the clustering of these traits remain unclear. We conducted GWAS of MetS in 1427 Africans from Ghana and Nigeria followed by replication testing and meta-analysis in another continental African sample from Kenya. Further replication testing was performed in an African American sample from the Atherosclerosis Risk in Communities (ARIC) study. We found two African-ancestry specific variants that were significantly associated with MetS: SNP rs73989312[A] near CA10 that conferred increased risk (P=3.86×10(-8), OR=6.80) and SNP rs77244975[C] in CTNNA3 that conferred protection against MetS (P=1.63×10(-8), OR=0.15). Given the exclusive expression of CA10 in the brain, our CA10 finding strengthens previously reported link between brain function and MetS. We also identified two variants that are not African specific: rs76822696[A] near RALYL associated with increased MetS risk (P=7.37×10(-9), OR=1.59) and rs7964157[T] near KSR2 associated with reduced MetS risk (P=4.52×10(-8), Pmeta=7.82×10(-9), OR=0.53). The KSR2 locus displayed pleiotropic associations with triglyceride and measures of blood pressure. Rare KSR2 mutations have been reported to be associated with early onset obesity and insulin resistance. Finally, we replicated the LPL and CETP loci previously found to be associated with MetS in Europeans. These findings provide novel insights into the genetics of MetS in Africans and demonstrate the utility of conducting trans-ethnic disease gene mapping studies for testing the cosmopolitan significance of GWAS signals of cardio-metabolic traits.
    No preview · Article · Oct 2015 · Molecular Genetics and Metabolism
  • Source
    • "The predominant underlying risk factor for the s MetS appear to be abdominal obesity678. However, not all obese develop the syndrome and even lean individuals can be insulin resistant, which was highly related with MetS[9]. The MetS can be clinically manifested in a variety of ways, which brings some difficulties for the clinical diagnosis of MetS. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Previous studies suggested that elevated liver enzymes could be used as potential novel biomarkers of Metabolic syndrome (MetS) and its clinical outcomes, although the results were inconsistent and the conclusions were underpowered. A case-control study with 6,268 MetS subjects and 6,330 frequency-matched healthy controls was conducted to systematically evaluated levels of four liver enzymes (ALT, AST, GGT and ALP), both in overall populations and in subjects with normal liver enzymes, with MetS risk using both quartiles and continuous unit of liver enzymes. We found significant associations were detected for all above analyses. Compared with quartile 1 (Q1), other quartiles have significant higher MetS risk, with ORs ranging from 1.15 to 18.15. The highest effected was detected for GGT, for which the OR value for the highest versus lowest quartile was 18.15 (95% CI: 15.7-20.9). Mutual adjustment proved the independence of the relations for all four liver enzymes. Sensitivity analyses didn't materially changed the trend. To the best of our knowledge, this study should be thelargest, which aimed at evaluating the association between liver enzymes measures and MetS risk. The results can better support that liver enzyme levels could be used as clinical predictors of MetS.
    Preview · Article · Sep 2015 · Oncotarget
Show more