Liver, Muscle, and Adipose Tissue Insulin Action Is Directly Related to Intrahepatic Triglyceride Content in Obese Subjects

Korenblat, Kevin; Fabbrini, Elisa; Mohammed, B. Selma; Klein, Samuel

doi:10.1053/j.gastro.2008.01.075

Cited by 512 publications

(446 citation statements)

References 39 publications

(3 reference statements)

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“…Nevertheless, cardiovascular diseases (CVD), including coronary heart disease and non-ischemic cardiomyopathy, are the leading cause of death in patients with NAFLD [1]. The pathophysiological hallmark of NAFLD is insulin resistance (IR), and the increase in intrahepatic triglycerides (IHTG) is directly related to the impairment of insulin action in the liver, skeletal muscle, and adipose tissue of obese subjects [3][4][5]; recently, the Framingham Heart Study has shown that IHTG content predicts the glucose and lipid abnormalities of the metabolic syndrome independently of visceral fat [6,7]. Furthermore, liver fat content is an independent indicator of myocardial IR and impaired coronary functional capacity in diabetic patients [8], thus suggesting that NAFLD is not merely a marker, but may be actively involved in the onset and progression of CVD.…”

Section: Introductionmentioning

confidence: 99%

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Salamone¹,

Galvano²,

Marino³

et al. 2012

Digestive and Liver Disease

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a b s t r a c tBackground: Nonalcoholic fatty liver disease is a chronic metabolic disorder with significant impact on cardiovascular and liver mortality. Aims: In this study, we examined the effects of silibinin on liver and myocardium injury in an experimental model of nonalcoholic fatty liver disease. Methods: A four-week daily dose of silibinin (20 mg/kg i.p.) was administrated to db/db mice fed a methionine-choline deficient diet. Hepatic and myocardial histology, oxidative stress and inflammatory cytokines were evaluated. Results: Silibinin administration decreased HOMA-IR, serum ALT and markedly improved hepatic and myocardial damage. Silibinin reduced isoprostanes, 8-deoxyguanosine and nitrites/nitrates in the liver and in the heart of db/db fed the methionine-choline deficient diet, whereas glutathione levels were restored to lean mice levels in both tissues. Consistently, liver mitochondrial respiratory chain activity was significantly impaired in untreated mice and was completely restored in silibinin-treated animals. TNF-␣ was increased whereas IL-6 was decreased both in the liver and heart of db/db fed methionine-choline deficient diet. Silibinin reversed heart TNF-␣ and IL-6 expression to control mice levels. Indeed, liver JNK phosphorylation was reduced to control levels in treated animals. Conclusions: This study demonstrates a combined effectiveness of silibinin on improving liver and myocardial injury in experimental nonalcoholic fatty liver disease.

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Section: Introductionmentioning

confidence: 99%

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Salamone¹,

Galvano²,

Marino³

et al. 2012

Digestive and Liver Disease

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show abstract

“…Many studies have shown that intra-hepatic and intra-myocellular lipid contents are closely related with insulin resistance and an adverse metabolic phenotype. [5][6][7] Thus, what seems to be more important than generalized adiposity is where the body fat is located. However, despite the importance of ectopic fat deposition, the association between fat deposition within muscle or liver and atherosclerosis or cardiovascular disease is yet to be fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

High fat stores in ectopic compartments in men with newly diagnosed type 2 diabetes: an anthropometric determinant of carotid atherosclerosis and insulin resistance

et al. 2009

Int J Obes

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Objective: The objective of this study was to analyze how fat partitioning in the liver, muscle and visceral compartments is altered by diabetes and age, and whether altered fat distribution is associated with a higher carotid artery intima-media thickness (C-IMT) and insulin resistance. Methods: This was an observational study performed on 21 young healthy men (mean age±s.d., 28.6±3.8 years) and 73 men with newly developed type 2 diabetes (38 young (29.2 ± 4.1 years) and 35 middle-aged (47.1 ± 6.0 years) subjects). Abdominal visceral and subcutaneous fat areas, mid-thigh muscle attenuation and liver attenuation characteristics were determined; the mid-thigh muscle was divided into low-and normal-density muscle areas. Results: The young and middle-aged diabetic subjects had higher visceral fat areas, higher liver attenuation and higher lipid-rich muscle (greater low-density muscle area and decreased muscle attenuation) when compared with healthy individuals; however, no differences were observed between the two diabetic groups. In contrast, the C-IMT increased with both age and diabetes. On the basis of multiple regression analyses, mid-thigh low-density muscle area and muscle attenuation were independently associated with the C-IMT, and the mid-thigh normal-density muscle area and muscle attenuation were independent factors of insulin resistance. Conclusions: High fat stores within ectopic compartments were observed at an early stage in the development of diabetes. Furthermore, altered lipid partitioning within muscle was independently associated with carotid atherosclerosis and insulin resistance.

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“…3,4 Hepatic lipid accumulation contributes to known metabolic alterations, such as insulin resistance, hyperglycemia, and hyperlipidemia. [5][6][7] NAFLD can be further divided into two major subtypes, which seem to have different outcomes: simple steatosis (NAFL) without liver inflammation or injury and nonalcoholic steatohepatitis (NASH). 8 NASH leads to liver cirrhosis 9 and to increased mortality more often than NAFL.…”

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confidence: 99%

Desmosterol in human nonalcoholic steatohepatitis

et al. 2013

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Dysregulation of the cholesterol synthesis pathway and accumulation of cholesterol in the liver are linked to the pathogenesis of nonalcoholic steatohepatitis (NASH). Therefore, we investigated the association of serum and liver levels of cholesterol precursors with NASH. Liver histology was assessed in 110 obese patients (Kuopio Obesity Surgery Study [KOBS] study, age 43.7 6 8.1 years [mean 6 standard deviation, SD], body mass index [BMI] 45.0 6 6.1 kg/m 2 ). Serum and liver levels of cholesterol precursors were measured with gas-liquid chromatography. The association between cholesterol precursors and serum alanine aminotransferase (ALT), as a marker of liver disease, was also investigated in a population cohort of 717 men (Metabolic Syndrome in Men Study [METSIM] study, age 57.6 6 5.8 years, BMI 27.1 6 4.0 kg/m 2 ). Serum desmosterol levels and the desmosterol-tocholesterol ratio were higher in individuals with NASH, but not in individuals with simple steatosis, compared to obese subjects with normal liver histology (P 5 0.002 and P 5 0.003, respectively). Levels of serum and liver desmosterol correlated strongly (r 5 0.667, P 5 1 3 10 29 ), suggesting a shared regulation. Both serum and liver desmosterol levels correlated positively with steatosis and inflammation in the liver (P < 0.05). Serum desmosterol had a higher correlation with the accumulation of cholesterol in the liver than serum cholesterol. Serum desmosterol levels (P 5 2 3 10 26 ) and the serum desmosterol-tocholesterol ratio (P 5 5 3 10 25 ) were associated with serum ALT in the population study. Conclusion: Levels of desmosterol in serum and the liver were associated with NASH. These results suggest that serum desmosterol is a marker of disturbed cholesterol metabolism in the liver. Whether desmosterol has a more specific role in the pathophysiology of NASH compared to other cholesterol precursors needs to be investigated. (HEPATOLOGY 2013;58:976-982)

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Liver, Muscle, and Adipose Tissue Insulin Action Is Directly Related to Intrahepatic Triglyceride Content in Obese Subjects

Cited by 512 publications

References 39 publications

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

Silibinin improves hepatic and myocardial injury in mice with nonalcoholic steatohepatitis

High fat stores in ectopic compartments in men with newly diagnosed type 2 diabetes: an anthropometric determinant of carotid atherosclerosis and insulin resistance

Desmosterol in human nonalcoholic steatohepatitis

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