The cross-sectional association between insulin resistance and circulating complement C3 is partly explained by plasma alanine aminotransferase, independent of central obesity and general inflammation (the CODAM study).

Background: Complement C3, a central component of the innate immune system is increased in subjects with obesity and type 2 diabetes and is a novel risk factor for cardiovascular disease. We hypothesized that the strong association between insulin resistance and circulating amounts of C3 may be related to hepatic fat accumulation -independent of central obesity itself and of a general low-grade inflammatory response.

Research Question: To what extent is the association between insulin resistance and C3 explained by plasma levels of alanine aminotransferase (ALT) as a surrogate of hepatic fat accumulation.

Five-year follow-up of waist circumference, insulin and ALT levels in familial combined hyperlipidaemia.

Introduction: Familial combined hyperlipidemia (FCHL), an entity with many features of the metabolic syndrome, is characterized by changes in cholesterol and triglyceride phenotype over time. This study was conducted to investigate the relation of alanineaminotransferase (ALT) levels, used as a surrogate for the amount of hepatic fat, with the switch in triglyceride phenotype and the increased susceptibility to develop hypertriglyceridemia in FCHL.

Methods: Body mass index, waist circumference, plasma triglycerides, insulin and ALT levels were measured in 145 FCHL family members and 54 spouses at baseline and after a five-year follow-up.

Activating transcription factor 6 polymorphisms and haplotypes are associated with impaired glucose homeostasis and type 2 diabetes in Dutch Caucasians.

Context: Activating transcription factor 6 (ATF6) is critical for initiation and full activation of the unfolded protein response. An association between genetic variation in ATF6 and type 2 diabetes (DM2) was recently reported in Pima Indians.

Objectives: To investigate the broader significance of this association for DM2, replication studies in distinct ethic populations are required.

Identification of novel molecular candidates for fatty liver in the hyperlipidemic mouse model, HcB19.

The inbred HcB19 mouse strain expresses a truncated form of thioredoxin interacting protein and is phenotypically characterized by fatty liver and elevated plasma triglycerides and VLDL. Recently, these mice have been proposed as an animal model for familial combined hyperlipidemia. The aim of the present study was identification of hepatic proteins specifically associated with the presence of fatty liver.

Variants in the PPARgamma gene affect fatty acid and glycerol metabolism in familial combined hyperlipidemia.

Familial combined hyperlipidemia (FCHL) is a common genetic lipid disorder characterized by premature coronary artery disease, dyslipidemia, insulin resistance, and impaired adipose tissue free fatty acid (FFA) metabolism. Increased adipose tissue FFA flux towards the liver may, in part, contribute to reduced insulin sensitivity and hyperlipidemia in FCHL. It was the objective of the present study to evaluate the contribution of the peroxisome proliferator-activated receptor gamma (PPARgamma) gene to FCHL traits related to adipocyte lipid metabolism, dyslipidemia, and insulin resistance.

Familial combined hyperlipidemia plasma stimulates protein secretion by HepG2 cells: identification of fibronectin in the differential secretion proteome.

The aim of this study was to evaluate whether soluble factors in plasma of familial combined hyperlipidemia (FCHL) patients affect hepatic protein secretion. Cultured human hepatocytes, i.e.