Anacetrapib reduces (V)LDL-cholesterol by inhibition of CETP activity and reduction of plasma PCSK9

Recently, we showed in APOE*3-Leiden.CETP mice that anacetrapib attenuated atherosclerosis development by reducing (V)LDL-C rather than by raising HDL-C. Here, we investigated the mechanism by which anacetrapib reduces (V)LDL-C and whether this effect was dependent on the inhibition of CETP. APOE*3-Leiden.CETP mice were fed a Western type diet...

Long-term niacin treatment induces insulin resistance and adrenergic responsiveness in adipocytes by adaptive downregulation of phosphodiesterase 3B

The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the...

RP105 deficiency aggravates cardiac dysfunction after myocardial infarction in mice

Background Toll-like receptor-4 (TLR4), a receptor of the innate immune system, is suggested to have detrimental effects on cardiac function after myocardial infarction (MI). RP105 (CD180) is a TLR4 homolog lacking the intracellular signaling domain that competitively inhibits TLR4-signaling. Thus, we hypothesized that RP105 deficiency, by...

P430RP105 deficiency aggravates cardiac dysfunction after myocardial infarction in mice

Purpose: Toll-like receptor-4 (TLR4), a receptor of the innate immune system, is suggested to have detrimental effects on cardiac function after myocardial infarction (MI). RP105 (CD180) is a TLR4 homolog lacking the intracellular signalling domain that competitively inhibits TLR4-signalling. Thus, we hypothesized that RP105 deficiency, by...

Exendin-4 decreases liver inflammation and atherosclerosis development simultaneously by reducing macrophage infiltration

Background and Purpose The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon...

The suprachiasmatic nucleus controls circadian energy metabolism and hepatic insulin sensitivity

Disturbances in the circadian system are associated with the development of type 2 diabetes mellitus. Here, we studied the direct contribution of the suprachiasmatic nucleus (SCN), the central pacemaker in the circadian system, in the development of insulin resistance. Exclusive bilateral SCN lesions in male C57Bl/6J mice, as verified by...

Estimation of activity related energy expenditure and resting metabolic rate in freely moving mice from indirect calorimetry data

Physical activity (PA) is a main determinant of total energy expenditure (TEE) and has been suggested to play a key role in body weight regulation. However, thus far it has been challenging to determine what part of the expended energy is due to activity in freely moving subjects. We developed a computational method to estimate activity related...

Reversal of hyperlipidaemia in apolipoprotein C1 transgenic mice by adenovirus-mediated gene delivery of the low-density-lipoprotein receptor, but not by the very-low-density-lipoprotein receptor

We have shown previously that human apolipoprotein (apo)Cl transgenic mice exhibit hyperlipidaemia, due primarily to an impaired clearance of very-low-density lipoprotein (VLDL) particles from the circulation. In the absence of at least the low-density-lipoprotein receptor (LDLR), it was shown that APOCI overexpression in transgenic mice...

Hyperlipoproteinemie en atherosclerose in transgene muizen ; preventie middels somatische gentherapie

Isolation and characterization of mouse lipoxygenase genes ; abstract

Genomic and cDNA cloning of a novel mouse lipoxygenase gene

A novel 12- and 15-lipoxygenase related gene was isolated from a mouse strain 129 genomic phage library in a screen with a human 15-lipoxygenase cDNA probe. The complete genomic sequence revealed 14 exons and 13 introns covering 7.3 kb of DNA. The splice junctions were verified from the cDNA sequences of a series of overlapping RT-PCR products....