title: Adrenal-specific scavenger receptor BI deficiency induces glucocorticoid insufficiency and lowers plasma very-low-density and low-density lipoprotein levels in mice.
abstract: OBJECTIVE
  We determined the physiological consequences of adrenocortical-specific deletion of scavenger receptor BI (SR-BI) function in C57BL/6 wild-type mice.
  
  
  RESULTS
  One adrenal from 10-day-old SR-BI knockout (KO) mice or wild-type controls was transplanted under the renal capsule of adrenalectomized C57BL/6 recipient mice. The fasting plasma corticosterone level increased over time in transplanted mice. Corticosterone values in SR-BI KO transplanted mice remained ≈50% lower (P<0.001) as compared with wild-type transplanted mice, which coincided with adrenocortical lipid depletion. A 6.5-fold higher (P<0.01) plasma adrenocorticotropic hormone level was present in SR-BI KO transplanted mice reminiscent of primary glucocorticoid insufficiency. On feeding with cholic acid-containing high cholesterol/high fat diet, SR-BI KO transplanted mice exhibited a 26% (P<0.05) reduction in their liver triglyceride level. Hepatic myosin regulatory light chain interacting protein/inducible degrader of the low-density lipoprotein receptor mRNA expression was 48% (P<0.01) decreased in adrenal-specific SR-BI KO mice, which was paralleled by a marked decrease (-46%; P<0.01) in proatherogenic very-low-density and low-density lipoprotein levels.
  
  
  CONCLUSIONS
  Adrenal-specific disruption of SR-BI function induces glucocorticoid insufficiency and lowers plasma very-low-density and low-density lipoprotein levels in atherogenic diet-fed C57BL/6 mice. These findings further highlight the interaction between adrenal high-density lipoprotein-cholesterol uptake by SR-BI, adrenal steroidogenesis, and the regulation of hepatic lipid metabolism.
authors.affiliation: Division of Biopharmaceutics, Leiden/Amsterdam Center for Drug Research, Gorlaeus Laboratories, PO Box 9502, 2300RA Leiden, The Netherlands. hoekstra@lacdr.leidenuniv.nl
authors.forename: Menno
authors.initials: M
authors.lastname: Hoekstra
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: van der Sluis
authors.forename: Miranda
authors.initials: M
authors.lastname: Van Eck
authors.forename: Theo J C
authors.initials: TJ
authors.lastname: Van Berkel
mesh_terms: D000311:Adrenal Glands / Q000378:metabolism* / Q000637:transplantation; D000309:Adrenal Insufficiency / Q000097:blood / Q000235:genetics / Q000378:metabolism*; D000315:Adrenalectomy; D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D002791:Cholesterol, Dietary / Q000097:blood; D003345:Corticosterone / Q000097:blood / Q000172:deficiency*; D004036:Diet, Atherogenic; D015536:Down-Regulation; D005215:Fasting / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation; D005838:Genotype; D008077:Lipoproteins, LDL / Q000097:blood*; D008079:Lipoproteins, VLDL / Q000097:blood*; D008099:Liver / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010641:Phenotype; D012333:RNA, Messenger / Q000378:metabolism; D051122:Scavenger Receptors, Class B / Q000172:deficiency* / Q000235:genetics; D015398:Signal Transduction; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
chemical_list: D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; C454739:Scarb1 protein, mouse; D051122:Scavenger Receptors, Class B; D014280:Triglycerides; D000324:Adrenocorticotropic Hormone; D003345:Corticosterone