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.
References
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Journal ArticleDOI
Nonalcoholic Steatohepatitis: Association of Insulin Resistance and Mitochondrial Abnormalities
Arun J. Sanyal,Carol Campbell-Sargent,Faridoddin Mirshahi,William B. Rizzo,Melissa J. Contos,Richard K. Sterling,Velimir A. Luketic,Mitchell L. Shiffman,John N. Clore +8 more
TL;DR: Data indicate that peripheral insulin resistance, increased fatty acid beta oxidation, and hepatic oxidative stress are present in both fatty liver and NASH, but NASH alone is associated with mitochondrial structural defects.
Journal ArticleDOI
Association of nonalcoholic fatty liver disease with insulin resistance
Giulio Marchesini,Mara Brizi,Antonio Maria Morselli-Labate,Giampaolo Bianchi,Elisabetta Bugianesi,Arthur J. McCullough,Gabriele Forlani,Nazario Melchionda +7 more
TL;DR: Nonalcoholic fatty liver disease is associated with insulin resistance and hyperinsulinemia even in lean subjects with normal glucose tolerance, and genetic factors that reduce insulin sensitivity and increase serum triglyceride levels may be responsible for its development.
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The natural history of nonalcoholic steatohepatitis: A follow‐up study of forty‐two patients for up to 21 years
Elizabeth E. Powell,W. Graham E. Cooksley,Reginald Hanson,Jeffrey Searle,June W. Halliday,W. Powell +5 more
TL;DR: In individual patients, poorly controlled diabetes and rapid weight loss preceded the onset of steatohepatitis, and in the patients with extensive fibrosis the the liver disease evolved from one of active inflammation to one of inactive cirrhosis without fat or inflammation.
Journal ArticleDOI
The expression of tumor necrosis factor in human adipose tissue. Regulation by obesity, weight loss, and relationship to lipoprotein lipase.
TL;DR: The data suggest that endogenous TNF expression in adipose tissue may help limit obesity in some subjects, perhaps by increasing insulin resistance and decreasing LPL.
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Fatty liver hepatitis (steatohepatitis) and obesity: an autopsy study with analysis of risk factors.
Ian R. Wanless,John S. Lentz +1 more
TL;DR: Statohepatitis (fatty liver hepatitis), histologically identical to alcoholic disease, occurs in some obese patients after jejunoileal bypass, and incidence of steatosis and steatohePatitis correlated with the degree of obesity.