Betaine for the prevention and treatment of insulin resistance and fatty liver in a high-fat dietary model of insulin resistance in C57BL mice.

Aim: The aim was to investigate mechanisms by which betaine improves hepatic insulin signaling in a dietary mouse model of insulin resistance and fatty liver.

Methods: C57BL 6J mice were fed a standard diet (SF), a standard diet with betaine (SFB), a nutritionally complete high fat (HF) diet, or a high fat diet with betaine (HFB) for 14 weeks. In a separate experiment, mice were fed high fat diet for 18 weeks, half of whom received betaine for the final 4 weeks.

Acetyl-L-carnitine and lipoic acid improve mitochondrial abnormalities and serum levels of liver enzymes in a mouse model of nonalcoholic fatty liver disease.

Mitochondrial abnormalities are suggested to be associated with the development of nonalcoholic fatty liver. Liver mitochondrial content and function have been shown to improve in oral feeding of acetyl-L-carnitine (ALC) to rodents. Carnitine is involved in the transport of acyl-coenzyme A across the mitochondrial membrane to be used in mitochondrial β-oxidation.

Betaine improves nonalcoholic fatty liver and associated hepatic insulin resistance: a potential mechanism for hepatoprotection by betaine.

Nonalcoholic fatty liver (NAFL) is a common liver disease, associated with insulin resistance. Betaine has been tested as a treatment for NAFL in animal models and in small clinical trials, with mixed results. The present study aims to determine whether betaine treatment would prevent or treat NAFL in mice and to understand how betaine reverses hepatic insulin resistance.

Oxidative stress and regulation of anti-oxidant enzymes in cytochrome P4502E1 transgenic mouse model of non-alcoholic fatty liver.

Background And Aim: Reactive oxygen species produced by cytochrome P4502E1 (CYP2E1) are believed to play a role in pathophysiology of non-alcoholic fatty liver disease (NAFLD). However, little is known about the expression, protein content and activity of anti-oxidant enzymes and the role of inducible nitric oxide synthase (iNOS), a source of reactive nitrogen species, in NAFLD. In the present study, we evaluate gene expression, protein content and activity of anti-oxidant enzymes, and iNOS, in a CYP2E1 overexpressing model of non-alcoholic fatty liver (NAFL).

Overexpression of liver-specific cytochrome P4502E1 impairs hepatic insulin signaling in a transgenic mouse model of nonalcoholic fatty liver disease.

Objective: Cytochrome P4502E1 (CYP2E1) expression in the liver is increased in nonalcoholic fatty liver disease. The aim of this study was to determine whether CYP2E1 overexpression in the liver interferes with insulin signaling pathways in a mouse model of nonalcoholic fatty liver disease.

Methods: Male mice containing the human CYP2E1 transgene under control of the mouse albumin enhancer-promoter (Tg) and control, nontransgenic mice were fed a diet containing 20% calories from fat for 8 months ad libitum.

The impact of CYP2E1 on the development of alcoholic liver disease as studied in a transgenic mouse model.

Background/aims: CYP2E1 metabolizes ethanol, generates reactive oxygen species, and is suggested to be important for development of alcoholic liver disease. The present study aims to evaluate the role of CYP2E1 in combination with ethanol for development of alcoholic liver disease using mice transgenic for the human CYP2E1 gene.

Methods: Changes in hepatic gene expression were monitored in controls and mice transgenic for human CYP2E1, treated with ethanol or isocaloric dextrose intragastrically for 4 weeks, and related to pathology using Affymetrix microarrays and TaqMan RealTime PCR.

Altered expression of transcription factors and genes regulating lipogenesis in liver and adipose tissue of mice with high fat diet-induced obesity and nonalcoholic fatty liver disease.

Objective: To determine whether expression of transcription factors and lipogenic enzymes is altered in liver and adipose tissue of mice with obesity, insulin resistance, and nonalcoholic fatty liver disease.

Methods: Mice were fed chow containing 9% of calories from standard fat (SF) or 20% of calories from high fat (HF) and killed after 9 months in the fasted or fed state.

Measurements: Liver injury was evaluated by histology and serum aminotransferase levels.

CYP2E1 inhibition enhances mallory body formation.

Mallory body (MB) formation is a complex phenomenon seen in chronic liver disease. CYP2E1 may play a role in preventing MB formation since it is involved in the elimination of toxic drugs and chemicals. When mice were fed with diethyl-1,4-dihydro-2,4,6-trimethyl-3,5-pyridinedicarboxylate (DDC) for 10 weeks, Mallory bodies (MBs) developed in the liver at the end of this period.

Production of a cytochrome P450 2E1 transgenic mouse and initial evaluation of alcoholic liver damage.

Hepatic metabolism of ethanol by cytochrome P450 2E1 (CYP2E1) is believed to contribute to alcoholic liver damage. To further evaluate CYP2E1 in alcoholic liver disease, we created a transgenic mouse containing human CYP2E1 complementary DNA (cDNA) under the control of mouse albumin enhancer-promoter. Two experiments were performed.