Search

Apolipoprotein D (ApoD) is lipocalin able to bind hydrophobic ligands. The APOD gene is upregulated in a number of pathologies, including Alzheimer's disease, Parkinson's disease, cancer, and hypothyroidism. Upregulation of ApoD is linked to decreased oxidative stress and inflammation in several models, including humans, mice, Drosophila melanogaster and plants. Studies suggest that the mechanism through which ApoD modulates oxidative stress and regulate inflammation is via its capacity to bind arachidonic acid (ARA). This polyunsaturated omega-6 fatty acid can be metabolised to generate large variety of pro-inflammatory mediators. ApoD serves as a sequester, blocking and/or altering arachidonic metabolism. In recent studies of diet-induced obesity, ApoD has been shown to modulate lipid mediators derived from ARA, but also from eicosapentaenoic acid and docosahexaenoic acid in an anti-inflammatory way. High levels of ApoD have also been linked to better metabolic health and inflammatory state in the round ligament of morbidly obese women. Since ApoD expression is upregulated in numerous diseases, it might serve as a therapeutic agent against pathologies aggravated by OS and inflammation such as many obesity comorbidities. This review will present the most recent findings underlying the central role of ApoD in the modulation of both OS and inflammation. [ABSTRACT FROM AUTHOR]

Plasma HDL-cholesterol concentrations correlate negatively with the risk of atherosclerotic cardiovascular disease (ASCVD). According to a widely cited model, HDL elicits its atheroprotective effect through its role in reverse cholesterol transport, which comprises the efflux of cholesterol from macrophages to early forms of HDL, followed by the conversion of free cholesterol (FCh) contained in HDL into cholesteryl esters, which are hepatically extracted from the plasma by HDL receptors and transferred to the bile for intestinal excretion. Given that increasing plasma HDL-cholesterol levels by genetic approaches does not reduce the risk of ASCVD, the focus of research has shifted to HDL function, especially in the context of macrophage cholesterol efflux. In support of the reverse cholesterol transport model, several large studies have revealed an inverse correlation between macrophage cholesterol efflux to plasma HDL and ASCVD. However, other studies have cast doubt on the underlying reverse cholesterol transport mechanism: in mice and humans, the FCh contained in HDL is rapidly cleared from the plasma (within minutes), independently of esterification and HDL holoparticle uptake by the liver. Moreover, the reversibility of FCh transfer between macrophages and HDL has implicated the reverse process - that is, the transfer of FCh from HDL to macrophages - in the aetiology of increased ASCVD under conditions of very high plasma HDL-FCh concentrations., (© 2021. Springer Nature Limited.)

Background. Experimental studies in animals suggest that apolipoprotein (apo) C-I is an important regulator of triglycerides in fasting and postprandial conditions and associated with carotid atherosclerosis. Methods. A cross-sectional study was conducted with 81 subjects, aged 56-80 years recruited from a population health survey. The participants underwent a fat tolerance test (1 g fat per Kg body weight) and carotid atherosclerosis was determined by ultrasound examination. VLDL particles, Sf 20-400, were isolated and their lipid composition and apoC-I content determined. Results. The carotid plaque area increased linearly with the number of apoC-I molecules per VLDL particles (P = 0.048) under fasting conditions. Fasting triglycerides increased across tertiles of apoC-I per VLDL particle in analyses adjusted for apoC-II and -C-III, apoE genotype and traditional cardiovascular risk factors (P = 0.011). The relation between apoC-I in VLDL and serum triglycerides was conveyed by triglyceride enrichment of VLDL particles (P for trend <0.001. The amount of apoC-I molecules per VLDL was correlated with the total (r = 0.41,P < 0.0001) and incremental (r = 0.35, P < 0.001) area under the postprandial triglyceride curve. Conclusions. Our findings support the concept that the content of apoC-I per VLDL particle is an important regulator of triglyceride metabolism in the fasting and postprandial state and associated with carotid athrosclerosis. [ABSTRACT FROM AUTHOR]

Apolipoprotein D (apoD), a widely expressed lipocalin, has the capacity to transport small hydrophobic molecules. Although it has been proposed that apoD may have multiple tissue-specific, physiological ligands and functions, these have yet to be identified. To gain insight in some of its functions, we generated transgenic mice over- expressing human apoD (H-apoD) under the control of neuron- specific promoters. In Thy-l/apoD and NSE/apoD mice, expression of H-apoD was strong in the nervous system although weakly detected in peripheral organs such as the liver and blood cells. These mice displayed not entirely anticipated metabolic defects. Although they are not obese and have normal lipid concentration in circulation, Thy-1/apoD and NSE/apoD mice are glucose intolerant, insulin resistant, and develop hepatic steatosis. The steatosis and its associated insulin resistance are correlated with impairments in hepatic lipogenesis. However, they are not strongly related with inflammation. This impaired insulin response is not caused by a decrease in circulating leptin or a modulation of adiponectin and resistin levels. These results suggest that variations in the levels and/or sites of apoD expression influence the lipid and glucose metabolism, consolidating apoD as a target for insulin-resistance-related disorders. [ABSTRACT FROM AUTHOR]