Dietary polyunsaturated fatty acids (PUFA) act as potent natural hypolipidemics and are linked to many health benefits in humans and in animal models. Mice fed long-term a high fat diet, in which medium-chain alpha linoleic acid (ALA) was partially replaced by long-chain docosahexaenoic (DHA) and eicosapentaenoic (EPA) fatty acids, showed reduced accumulation of body fat and prevention of insulin resistance, besides increased mitochondrial beta-oxidation in white adipose tissue and decreased plasma lipids. ALA, EPA and DHA all belong to PUFA of n-3 series. The intestine is a gatekeeper organ for ingested lipids. To examine the potential contribution of the intestine in the beneficial effects of EPA and DHA, this study assessed gene expression changes using whole genome microarray analysis on small intestinal scrapings. The main biological process affected was lipid metabolism. Fatty acid uptake, peroxisomal and mitochondrial beta-oxidation, and omega-oxidation of fatty acids were all increased. Quantitative real time PCR and intestinal fatty acid oxidation measurements ([14C(U)]-palmitate) confirmed significant gene expression differences in a dose-dependent manner. Furthermore, no major changes in the expression of lipid metabolism genes were observed in colonic scrapings. In conclusion, we show that marine n-3 fatty acids regulate small intestinal gene expression patterns. Since this organ contributes significantly to whole organism energy use, this adaptation of the small intestine may contribute to the complex and observed beneficial physiological effects of these natural compounds under conditions that will normally lead to development of obesity and diabetes.
Induction of lipid oxidation by polyunsaturated fatty acids of marine origin in small intestine of mice fed a high-fat diet.
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View SamplesThe role of PDK1 on mammary tumorigenesis and its interaction with PPARdelta, was assessed. Transgenic mice were generated in which PDK1 was expressed in the mammary epithelium.
PPARĪ“ activation acts cooperatively with 3-phosphoinositide-dependent protein kinase-1 to enhance mammary tumorigenesis.
Specimen part, Treatment
View SamplesNotch1 deficient hair matrix keratinocytes have lower mitotic rates, resulting in smaller follicles with fewer cells. In addition, the ratio of melanocytes to keratinocytes is greatly reduced. Microarray was performed to study downstream mechanism of Notch1-deficiency
Bi-compartmental communication contributes to the opposite proliferative behavior of Notch1-deficient hair follicle and epidermal keratinocytes.
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View SamplesThe glomerular filtration barrier prevents large serum proteins from being lost into the urine. It is not known, however, why the filter does not routinely clog with large proteins that enter the glomerular basement membrane (GBM). Here we provide evidence that an active transport mechanism exists to remove immunoglobulins that accumulate at the filtration barrier. We found that FcRn, an IgG and albumin transport receptor, is expressed in podocytes and functions to internalize IgG from the GBM. Mice lacking FcRn accumulated IgG in the GBM as they aged and tracer studies showed delayed clearance of IgG from the kidneys of FcRn deficient mice. Supporting a role for this pathway in disease, saturating the clearance mechanism potentiated the pathogenicity of nephrotoxic sera. These studies support the idea that podocytes play an active role in removing proteins from the GBM and suggest that genetic or acquired impairment of the clearance machinery is likely to be a common mechanism promoting glomerular diseases.
Podocytes use FcRn to clear IgG from the glomerular basement membrane.
Specimen part
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