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- Galman, C, et al.
(author)
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Age-induced hypercholesterolemia in the rat relates to reduced elimination but not increased intestinal absorption of cholesterol
- 2007
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 293:3, s. E737-E742
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Journal article (peer-reviewed)abstract
- Plasma cholesterol increases in normal aging in both rodents and humans. This is associated with reduced elimination of cholesterol as bile acids (BAs) and decreased receptor-mediated clearance of plasma LDL, changes that can be reversed by treatment with growth hormone (GH). The level of intestinal absorption of cholesterol may also contribute to the development of hypercholesterolemia. In this study, we investigated whether cholesterol absorption increases with age and whether any such age-related change could be influenced by treatment with GH or ezetimibe (EZE). Male rats aged 6 and 18 mo were studied with and without GH or EZE treatment. BA synthesis was reduced and plasma cholesterol was increased in the old animals, whereas cholesterol absorption was unaltered. Cholesterol absorption was not altered by GH treatment but was reduced by EZE in both groups of animals. Hepatic LDL receptors (LDLRs), scavenger receptor class B type 1, and proprotein convertase subtilisin/kexin type 9 serine protease (PCSK9) transcripts were unchanged in old animals. GH treatment induced LDLRs, PCSK9 transcripts, and BA synthesis. We conclude that the age-induced hypercholesterolemia in the rat and its reversal by GH treatment relates to altered degradation of cholesterol in the liver and is not due to changes in cholesterol absorption.
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- Persson, L, et al.
(author)
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Importance of proprotein convertase subtilisin/kexin type 9 in the hormonal and dietary regulation of rat liver low-density lipoprotein receptors
- 2009
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In: Endocrinology. - : The Endocrine Society. - 1945-7170 .- 0013-7227. ; 150:3, s. 1140-1146
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Journal article (peer-reviewed)abstract
- Hormonal or dietary challenge can stimulate hepatic low-density lipoprotein receptor (LDLR) expression through posttranscriptional mechanisms. We here tested whether such observations may be due to regulation of proprotein convertase subtilisin/kexin type 9 (PCSK9). Treatment with glucagon resulted in a 2-fold increase in hepatic LDLR protein expression, whereas its mRNA levels were reduced; this occurred simultaneously with a 70% reduction in PCSK9 expression. Insulin treatment resulted in responses opposite to those seen by treatment with glucagon. Furthermore, high-dose ethinylestradiol treatment reduced PCSK9 expression by half. Finally, feeding of rats with dietary cholesterol reduced PCSK9 expression, resulting in an increased number of hepatic LDLRs despite a reduction of LDLR mRNA levels. Regulation of PCSK9 occurred in part through sterol regulatory element binding protein-2, but changes in this cholesterol-controlled transcription factor could not explain all hormonal effects seen. We conclude that the hormonal and dietary regulation of hepatic LDLRs also involves posttranscriptional regulation by PCSK9. The identification of PCSK9 regulation by these various treatments is important in understanding of the physiological function of this protein and points to new targets for therapeutic treatments to increase hepatic LDLR numbers.PCSK9, which reduces LDL-receptors by posttranscriptional mechanisms, is involved in the hormonal stimulation of LDL receptors by glucagon and estrogens.
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- Valdés-Correcher, Elena, et al.
(author)
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Herbivory on the pedunculate oak along an urbanization gradient in Europe : Effects of impervious surface, local tree cover, and insect feeding guild
- 2022
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In: Ecology and Evolution. - : Wiley. - 2045-7758. ; 12:3
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Journal article (peer-reviewed)abstract
- Urbanization is an important driver of the diversity and abundance of tree-associated insect herbivores, but its consequences for insect herbivory are poorly understood. A likely source of variability among studies is the insufficient consideration of intra-urban variability in forest cover. With the help of citizen scientists, we investigated the independent and interactive effects of local canopy cover and percentage of impervious surface on insect herbivory in the pedunculate oak (Quercus robur L.) throughout most of its geographic range in Europe. We found that the damage caused by chewing insect herbivores as well as the incidence of leaf-mining and gall-inducing herbivores consistently decreased with increasing impervious surface around focal oaks. Herbivory by chewing herbivores increased with increasing forest cover, regardless of impervious surface. In contrast, an increase in local canopy cover buffered the negative effect of impervious surface on leaf miners and strengthened its effect on gall inducers. These results show that—just like in non-urban areas—plant–herbivore interactions in cities are structured by a complex set of interacting factors. This highlights that local habitat characteristics within cities have the potential to attenuate or modify the effect of impervious surfaces on biotic interactions.
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