Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD

Bril, Fernando; Sninsky, John J.; Baca, Arthur M.; Superko, H. Robert; Sanchez, Paola Portillo; Biernacki, Diane; Maximos, Maryann; Lomonaco, Romina; Orsak, Beverly; Suman, Amitabh; Weber, Michelle; McPhaul, Michael J.; Cusi, Kenneth

doi:10.1210/jc.2015-3111

Cited by 135 publications

(92 citation statements)

References 39 publications

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“…We observed that HFCS diet has minimal impact on serum TG levels, presumably due to rapid catabolism of VLDL. However, there was a dramatic increase LDL cholesterol levels upon chronic HFCS diet (Table ), supporting the notion that NAFLD was associated with increased risk of cardiovascular diseases . The supplementation with γT3 decreased LDL content by one third, which might be due to the reduced hepatic TG content.…”

Section: Discussionsupporting

confidence: 62%

Gamma‐Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice

Kim

Natarajan

Chung

2018

Molecular Nutrition Food Res

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Section: Discussionsupporting

confidence: 62%

Gamma‐Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice

Kim

Natarajan

Chung

2018

Molecular Nutrition Food Res

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“…Evidence has shown that NAFLD is an independent risk factor of atherogenic dyslipidemia in various clinical studies [1819]. Hamsters easily develop insulin resistance and dyslipidemia after several weeks of being fed a high-fructose diet.…”

Section: Targeting Scap In Animal Models Of Insulin Resistancementioning

confidence: 99%

The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis

Moon

2017

Endocrinol Metab

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Nonalcoholic fatty liver disease (NAFLD) is strongly associated with insulin resistance, obesity, and dyslipidemia. NAFLD encompasses a wide range of states from the simple accumulation of triglycerides in the hepatocytes to serious states accompanied by inflammation and fibrosis in the liver. De novo lipogenesis has been shown to be a significant factor in the development of hepatic steatosis in insulin-resistant states. Sterol regulatory element binding protein-1c (SREBP-1c) is the main transcription factor that mediates the activation of lipogenesis, and SREBP cleavage activating protein (SCAP) is required for the activation of SREBPs. Here, recent animal studies that suggest SCAP as a therapeutic target for hepatic steatosis and hypertriglyceridemia are discussed.

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“…The highest mortality in NAFLD/NASH arises not from end-stage liver disease, or an increased risk of hepatocellular carcinoma (HCC), but secondary to cardiovascular disease [8, 9]. This may be explained by worse atherogenic risk factors such as hyperglycemia, hyperinsulinemia [10] and dyslipidemia [11], among others.…”

Section: Introductionmentioning

confidence: 99%

Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2 Diabetes Mellitus

Portillo-Sánchez

Cusi

2016

Clin Diabetes Endocrinol

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Nonalcoholic fatty liver disease (NAFLD) is believed to be the most common chronic liver disease, affecting at least one-third of the population worldwide. The more aggressive form is known as nonalcoholic steatohepatitis (NASH) and characterized by hepatocyte necrosis and inflammation. The presence of fibrosis is not uncommon. Fibrosis indicates a more aggressive course and patients with NASH that are at high-risk of cirrhosis and premature mortality, as well as at increased risk of hepatocellular carcinoma (HCC). Patients with type 2 diabetes mellitus (T2DM) are at the highest risk for the development of NASH, even in the setting of normal plasma aminotransferase levels. The presence of dysfunctional adipose tissue in most overweight and obese subjects, combined with insulin resistance, hyperglycemia, and atherogenic dyslipidemia, contribute to their increased cardiovascular risk. Many therapeutic agents have been tested for the treatment of NASH but few studies have focused in patients with T2DM. At the present moment, the only FDA-approved agents that in controlled studies have shown to significantly improve liver histology in patients with diabetes are pioglitazone and liraglutide. Current research efforts are centering on the mechanisms for intrahepatic triglyceride accumulation and for the development of steatohepatitis, the role of mitochondrial dysfunction in NASH, and the impact of improving glycemic control per se on the natural history of the disease. This brief review summarizes our current knowledge on the pharmacological agents available for the treatment of NASH to assist healthcare providers in the management of these challenging patients.

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Hepatic Steatosis and Insulin Resistance, But Not Steatohepatitis, Promote Atherogenic Dyslipidemia in NAFLD

Cited by 135 publications

References 39 publications

Gamma‐Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice

Gamma‐Tocotrienol Attenuates the Hepatic Inflammation and Fibrosis by Suppressing Endoplasmic Reticulum Stress in Mice

The SCAP/SREBP Pathway: A Mediator of Hepatic Steatosis

Treatment of Nonalcoholic Fatty Liver Disease (NAFLD) in patients with Type 2 Diabetes Mellitus

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