Nonalcoholic fatty liver disease a feature of the metabolic syndrome
Giulio Marchesini,Mara Brizi,Giampaolo Bianchi,Sara Tomassetti,Elisabetta Bugianesi,Marco Lenzi,Arthur J. McCullough,S. Natale,Gabriele Forlani,Nazario Melchionda +9 more
TLDR
It is concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity.Abstract:
Insulin sensitivity (euglycemic clamp, insulin infusion rate: 40 mU m(-2) min(-1)) was studied in 30 subjects with biopsy-proven nonalcoholic fatty liver disease (NAFLD), normal glucose tolerance, and a BMI <30 kg/m(2) Of those 30 subjects, 9 had pure fatty liver and 21 had evidence of steatohepatitis In addition, 10 patients with type 2 diabetes under good metabolic control and 10 healthy subjects were studied Most NAFLD patients had central fat accumulation, increased triglycerides and uric acid, and low HDL cholesterol, irrespective of BMI Glucose disposal during the clamp was reduced by nearly 50% in NAFLD patients, as well as in patients with normal body weight, to an extent similar to that of the type 2 diabetic patients Basal free fatty acids were increased, whereas insulin-mediated suppression of lipolysis was less effective (-69% in NAFLD vs -84% in control subjects; P = 0003) Postabsorptive hepatic glucose production (HGP), measured by [6,6-(2)H(2)]glucose, was normal In response to insulin infusion, HGP decreased by only 63% of basal in NAFLD vs 84% in control subjects (P = 0002) Compared with type 2 diabetic patients, NAFLD patients were characterized by lower basal HGP, but with similarly reduced insulin-mediated suppression of HGP There was laboratory evidence of iron overload in many NAFLD patients, but clinical, histological, and biochemical data (including insulin sensitivity) were not correlated with iron status Four subjects were heterozygous for mutation His63Asp of the HFE gene of familiar hemochromatosis We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is characterized by clinical and laboratory data similar to those found in diabetes and obesity NAFLD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistanceread more
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Design and validation of a histological scoring system for nonalcoholic fatty liver disease
David E. Kleiner,Elizabeth M. Brunt,Mark L. Van Natta,Cynthia Behling,Melissa J. Contos,Oscar W. Cummings,Linda D. Ferrell,Yao Chang Liu,Michael Torbenson,Aynur Unalp-Arida,Matthew M. Yeh,Arthur J. McCullough,Arun J. Sanyal +12 more
TL;DR: A strong scoring system and NAS for NAFLD and NASH with reasonable inter‐rater reproducibility that should be useful for studies of both adults and children with any degree ofNAFLD are presented.
Journal ArticleDOI
SREBPs: activators of the complete program of cholesterol and fatty acid synthesis in the liver
TL;DR: The complex, interdigitated roles of these three SREBPs have been dissected through the study of ten different lines of gene-manipulated mice and form the subject of this review.
Journal ArticleDOI
Prevalence of hepatic steatosis in an urban population in the United States: Impact of ethnicity
Jeffrey D. Browning,Lidia S. Szczepaniak,Robert L. Dobbins,Pamela Nuremberg,Jay D. Horton,Jonathan Cohen,Scott M. Grundy,Helen H. Hobbs +7 more
TL;DR: The prevalence of hepatic steatosis was greater in men than women among whites, but not in blacks or Hispanics, and significant ethnic and sex differences in the prevalence may have a profound impact on susceptibility to Steatosis‐related liver disease.
Journal ArticleDOI
Sources of fatty acids stored in liver and secreted via lipoproteins in patients with nonalcoholic fatty liver disease.
Kerry L. Donnelly,Coleman Smith,Sarah Jane Schwarzenberg,Jose Jessurun,Mark D. Boldt,Elizabeth J. Parks +5 more
TL;DR: In this article, the authors quantified the biological sources of hepatic and plasma lipoprotein TAG in NAFLD patients, using stable isotopes for four days to label and track serum nonesterified fatty acids (NEFAs), dietary fatty acids, and those derived from the de novo lipogenesis (DNL) pathway, present in liver tissue and lipid TAG.
Journal ArticleDOI
Pioglitazone, Vitamin E, or Placebo for Nonalcoholic Steatohepatitis
Arun J. Sanyal,Naga Chalasani,Kris V. Kowdley,Arthur J. McCullough,Anna Mae Diehl,Nathan M. Bass,Brent A. Neuschwander-Tetri,Joel E. Lavine,James Tonascia,Aynur Unalp,Mark L. Van Natta,Jeanne M. Clark,Elizabeth M. Brunt,David E. Kleiner,Jay H. Hoofnagle,Patricia R. Robuck +15 more
TL;DR: Vitamin E was superior to placebo for the treatment of nonalcoholic steatohepatitis in adults without diabetes, and significant benefits of pioglitazone were observed for some of the secondary outcomes.
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Increased hepatic iron concentration in nonalcoholic steatohepatitis is associated with increased fibrosis
D. K. George,S. Goldwurm,Graeme A. Macdonald,L. L. Cowley,Neal I. Walker,Ward Pj,E C Jazwinska,L. W. Powell +7 more
TL;DR: The Cys282Tyr mutation is responsible for most of the mild iron overload found in NASH and thus has a significant association with hepatic damage in these patients, which cannot always be considered benign.
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Liver Pathology and the Metabolic Syndrome X in Severe Obesity
Picard Marceau,Simon Biron,Frédéric-Simon Hould,Simon Marceau,Serge Simard,Swan N. Thung,John G. Kral +6 more
TL;DR: It is concluded that the metabolic syndrome via impaired glucose tolerance is strongly correlated with steatosis, fibrosis, and cirrhosis of the liver.