Evaluation and management of obesity-related nonalcoholic fatty liver disease

Nugent, Clare; Younossi, Zobair M.

doi:10.1038/ncpgasthep0879

Cited by 89 publications

(56 citation statements)

References 96 publications

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“…Hepatic steatosis is also known to exacerbate insulin resistance in obesity and cause liver dysfunction, such as nonalcoholic steatohepatitis (33). In the liver of Pik3cg −/− mice, expression of Pparg and Cidec is significantly decreased without any alterations in genes involved in fatty acid synthesis, whereas genes regulating β-oxidation, such as Cpt1a, are up-regulated, consistent with the previous report that Fsp27 suppresses β-oxidation and triglyceride turnover in hepatocytes (21).…”

Section: -8) (E) Phosphorylation Of Akt In Livers and Skeletal Musclsupporting

confidence: 80%

Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance

Kobayashi¹,

Ueki

Okazaki³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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Obesity and insulin resistance, the key features of metabolic syndrome, are closely associated with a state of chronic, lowgrade inflammation characterized by abnormal macrophage infiltration into adipose tissues. Although it has been reported that chemokines promote leukocyte migration by activating class IB phosphoinositide-3 kinase (PI3Kγ) in inflammatory states, little is known about the role of PI3Kγ in obesity-induced macrophage infiltration into tissues, systemic inflammation, and the development of insulin resistance. In the present study, we used murine models of both diet-induced and genetically induced obesity to examine the role of PI3Kγ in the accumulation of tissue macrophages and the development of obesity-induced insulin resistance. Mice lacking p110γ (Pik3cg −/− ), the catalytic subunit of PI3Kγ, exhibited improved systemic insulin sensitivity with enhanced insulin signaling in the tissues of obese animals. In adipose tissues and livers of obese Pik3cg −/− mice, the numbers of infiltrated proinflammatory macrophages were markedly reduced, leading to suppression of inflammatory reactions in these tissues. Furthermore, bone marrow-specific deletion and pharmacological blockade of PI3Kγ also ameliorated obesity-induced macrophage infiltration and insulin resistance. These data suggest that PI3Kγ plays a crucial role in the development of both obesity-induced inflammation and systemic insulin resistance and that PI3Kγ can be a therapeutic target for type 2 diabetes.

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Section: -8) (E) Phosphorylation Of Akt In Livers and Skeletal Musclsupporting

confidence: 80%

Blockade of class IB phosphoinositide-3 kinase ameliorates obesity-induced inflammation and insulin resistance

Kobayashi¹,

Ueki

Okazaki³

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

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“…The analysis of NAFLD using liver biopsy is the gold standard for evaluating this disease state and there are limited prospective randomized data in the literature utilizing liver histology to assess the effect of lifestyle modification in NAFLD to include NASH [Neuschwander-Tetri, 2005;Angulo et al 2007;Youssef and McCullough, 2002;Nugent and Younossi, 2007]. This study involved a multidisciplinary team for health screening and lifestyle modification implementation.…”

Section: Discussionmentioning

confidence: 99%

Prospective histopathologic evaluation of lifestyle modification in nonalcoholic fatty liver disease: a randomized trial

Eckard¹,

Cole²,

Lockwood

et al. 2013

Therap Adv Gastroenterol

130

134

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Background and aims: Nonalcoholic fatty liver disease (NAFLD) is now recognized as part of the metabolic syndrome, and is specifically related to obesity and insulin resistance. Lifestyle modification is advocated for the treatment of NAFLD, but few studies have evaluated its impact on liver histology. The purpose of this study was to investigate which, if any, specific diet and exercise recommendations are associated with histopathologic changes. Methods: A total of 56 participants were randomly assigned to 1 of 4 lifestyle modification subgroups for 6 months: standard care, low-fat diet and moderate exercise, moderate-fat/lowprocessed-carbohydrate diet and moderate exercise, or moderate exercise only. All subjects had biopsy-proven NAFLD, to include nonalcoholic steatohepatitis (NASH), and received a repeat 6-month biopsy to detect histopathologic changes. Other measures included blood assay of liver enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase), fasting glucose, serum insulin, lipid panel, body weight, dietary intake, fat mass, and fitness level. Results: Among the 41 participants who completed the study (88% with NASH), a significant change was found in pre-to post-NAFLD activity score in the group as a whole (p < 0.001) with no difference detected between subgroups (p = 0.31). Our results confirm that lifestyle modification is effective in improving NAFLD and NASH. Conclusions: Regardless of intervention group, lifestyle modification improved liver histology, as verified by repeat biopsy, after a 6-month intervention. This study reinforces the importance of lifestyle modification as the primary treatment strategy for patients with NAFLD.

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“…5 The clinicopathologic spectrum of NAFLD ranges from steatosis or fatty liver, a reversible disorder to steatosis with inflammation and fibrosis-nonalcoholic steatohepatitis (NASH) to cirrhosis or hepatocellular carcinoma. 8 The progression of steatosis to steatohepatitis is two hit process, proposed by Day and James in 1998. 9 Fat accumulation in the liver is the first hit; a consequence of the imbalance between triglyceride accumulation on one hand and lipid betaoxidation and export on the other.…”

Section: Introductionmentioning

confidence: 99%