The Metabolic Syndrome and Its Influence on Nonalcoholic Steatohepatitis

Kanwar, Pushpjeet; Kowdley, Kris V.

doi:10.1016/j.cld.2015.10.002

Cited by 101 publications

(84 citation statements)

References 135 publications

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“…Metabolic syndrome represents a cluster of metabolic abnormalities including obesity, hypertension, dyslipidemia, and insulin resistance with obesity and insulin resistance recognized as the causative factors 1–3 . Together, these derangements present a significant risk for nonalcoholic steatohepatitis, atherosclerosis, and diabetes, all of which lead to cardiovascular complications.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet

Sodhi¹,

Srikanthan²,

Goguet-Rubio³

et al. 2017

Sci Rep

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We have previously reported that the α1 subunit of sodium potassium adenosine triphosphatase (Na/K-ATPase), acts as a receptor and an amplifier for reactive oxygen species, in addition to its distinct pumping function. On this background, we speculated that blockade of Na/K-ATPase-induced ROS amplification with a specific peptide, pNaKtide, might attenuate the development of steatohepatitis. To test this hypothesis, pNaKtide was administered to a murine model of NASH: the C57Bl6 mouse fed a “western” diet containing high amounts of fat and fructose. The administration of pNaKtide reduced obesity as well as hepatic steatosis, inflammation and fibrosis. Of interest, we also noted marked improvement in mitochondrial fatty acid oxidation, insulin sensitivity, dyslipidemia and aortic streaking in this mouse model. To further elucidate the effects of pNaKtide on atherosclerosis, similar studies were performed in ApoE knockout mice also exposed to the western diet. In these mice, pNaKtide not only improved steatohepatitis, dyslipidemia, and insulin sensitivity, but also ameliorated significant aortic atherosclerosis. Collectively, this study demonstrates that the Na/K-ATPase/ROS amplification loop contributes significantly to the development and progression of steatohepatitis and atherosclerosis. And furthermore, this study presents a potential treatment, the pNaKtide, for the metabolic syndrome phenotype.

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Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet

Sodhi¹,

Srikanthan²,

Goguet-Rubio³

et al. 2017

Sci Rep

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show abstract

“…For the sake of terminology, NAFLD is comprised of non-alcoholic fatty liver (NAFL) and non-alcoholic steatohepatitis (NASH)[1]. NAFL is characterized by steatosis of the liver, involving greater than 5% of parenchyma, with no evidence of hepatocyte injury[2]. Whereas, NASH is defined by histologic terms, that is a necroinflammatory process whereby the liver cells become injured in a background of steatosis[2].…”

Section: Introductionmentioning

confidence: 99%

Non-alcoholic fatty liver disease: An expanded review

Benedict

Zhang

2017

WJH

626

494

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Non-alcoholic fatty liver disease (NAFLD) encompasses the simple steatosis to more progressive steatosis with associated hepatitis, fibrosis, cirrhosis, and in some cases hepatocellular carcinoma. NAFLD is a growing epidemic, not only in the United States, but worldwide in part due to obesity and insulin resistance leading to liver accumulation of triglycerides and free fatty acids. Numerous risk factors for the development of NAFLD have been espoused with most having some form of metabolic derangement or insulin resistance at the core of its pathophysiology. NAFLD patients are at increased risk of liver-related as well as cardiovascular mortality, and NAFLD is rapidly becoming the leading indication for liver transplantation. Liver biopsy remains the gold standard for definitive diagnosis, but the development of noninvasive advanced imaging, biochemical and genetic tests will no doubt provide future clinicians with a great deal of information and opportunity for enhanced understanding of the pathogenesis and targeted treatment. As it currently stands several medications/supplements are being used in the treatment of NAFLD; however, none seem to be the “magic bullet” in curtailing this growing problem yet. In this review we summarized the current knowledge of NAFLD epidemiology, risk factors, diagnosis, pathogenesis, pathologic changes, natural history, and treatment in order to aid in further understanding this disease and better managing NAFLD patients.

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“…In the mitochondrial outer membrane, fatty acids and CoA must be converted to acyltransferases by CPT-I. Once inside the mitochondrial matrix, CPT-II generates acyl-CoAs from acylcarnitines to initiate the β-oxidation of fatty acids to acetyl-CoA[28,29]. Then, carnitine crosses the mitochondrial inner membrane and binds with the endogenous or exogenous acyl-CoA to prevent the accumulation of acyl-CoA and subsequent cell poisoning.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial carnitine palmitoyl transferase-II inactivity aggravates lipid accumulation in rat hepatocarcinogenesis

Yao

Yang

et al. 2017

WJG

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AIMTo investigate the dynamic alteration of mitochondrial carnitine palmitoyl transferase II (CPT-II) expression during malignant transformation of rat hepatocytes.METHODSSprague-Dawley male rats were fed with normal, high fat (HF), and HF containing 2-fluorenylacetamide (2-FAA) diet, respectively. According to the Hematoxylin and Eosin staining of livers, rats were divided into control, fatty liver, degeneration, precancerous, and cancerous groups. Liver lipids were dyed with Oil Red O, CPT-II alterations were analyzed by immunohistochemistry, and compared with CPT-II specific concentration (μg/mg protein). Levels of total cholesterol (Tch), triglyceride (TG), and amino-transferases [alanine aminotransferase (ALT), aspartate aminotransferase (AST)] were determined by the routine methods.RESULTSAfter intake of HF and/or HF+2-FAA diets, the rat livers showed mass lipid accumulation. The lipid level in the control group was significantly lower than that in other groups. The changes of serum TG and Tch levels were abnormally increasing, 2-3 times more than those in the controls (P < 0.05). During the rat liver morphological changes from normal to cancer development process with hepatocyte injury, serum AST and ALT levels were significantly higher (4-8 times, P < 0.05) than those in the control group. The specific concentration of CPT-II in liver tissues progressively decreased during hepatocyte malignant transformation, with the lowest CPT-II levels in the cancer group than in any of the other groups (P < 0.05).CONCLUSIONLow CPT-II expression might lead to abnormal hepatic lipid accumulation, which should promote the malignant transformation of hepatocytes.

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The Metabolic Syndrome and Its Influence on Nonalcoholic Steatohepatitis

Cited by 101 publications

References 135 publications

RETRACTED ARTICLE: pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet

RETRACTED ARTICLE: pNaKtide Attenuates Steatohepatitis and Atherosclerosis by Blocking Na/K-ATPase/ROS Amplification in C57Bl6 and ApoE Knockout Mice Fed a Western Diet

Non-alcoholic fatty liver disease: An expanded review

Mitochondrial carnitine palmitoyl transferase-II inactivity aggravates lipid accumulation in rat hepatocarcinogenesis

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