Menno Hoekstra

Publications (55) View all

• Article: High-density lipoprotein as a source of cholesterol for adrenal steroidogenesis; a study in individuals with low plasmsa HDL-C.

  Andrea E Bochem, Adriaan G Holleboom, Johannes A Romijn, Menno Hoekstra, Geesje M Dallinga-Thie, Mahdi M Motazacker, G Kees Hovingh, Jan A Kuivenhoven, Erik S G Stroes
  [show abstract] [hide abstract]
  ABSTRACT: Few studies have addressed the delivery of lipoprotein derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL) it is unresolved whether high-density lipoprotein (HDL) contributes to adrenal steroidogenesis. To study this, steroid hormone profiles in urine were assessed in male subjects suffering from functional mutations in ATP-binding cassette transporter A1 (ABCA1; n=24), lecithin cholesterol:acyltransferase (LCAT; n=40) as well as in 11 subjects with low HDL-C without ABCA1/LCAT mutations. HDL-C levels were 39% lower in the ABCA1, LCAT and low HDL-C group, compared to controls (all p<0.001). In all groups with low HDL-C levels, urinary excretion of 17-ketogenic steroids was reduced by 33%, 27% and 32% compared to controls (all p<0.04). In 7 carriers of either type of mutation, ACTH stimulation did not reveal differences from normolipidemic controls. In conclusion, this study shows that basal but not stimulated corticosteroid metabolism is attenuated in subjects with low HDL-C, irrespective of its molecular origin. These findings lend support to a role for HDL as cholesterol donor for basal adrenal steroidogenesis in humans.
  The Journal of Lipid Research 03/2013; · 5.56 Impact Factor
• Article: Nuclear receptor atlas of female mouse liver parenchymal, endothelial, and Kupffer cells.

  Zhaosha Li, J Kar Kruijt, Ronald J van der Sluis, Theo J C Van Berkel, Menno Hoekstra
  [show abstract] [hide abstract]
  ABSTRACT: The liver consists of different cells types which together synchronize crucial roles in liver homeostasis. Since nuclear receptors constitute an important class of drug targets that are involved in a wide variety of physiological processes, we have composed the hepatic cell type-specific expression profile of nuclear receptors to uncover the pharmacological potential of liver-enriched nuclear receptors. Parenchymal liver cells (hepatocytes) and liver endothelial and Kupffer cells were isolated from virgin female C57BL/6 wild-type mice using collagenase perfusion and counter-flow centrifugal elutriation. The hepatic expression pattern of 49 nuclear receptors was generated by real-time quantitative PCR using the NUclear Receptor Signaling Atlas (NURSA) program resources. Thirty six nuclear receptors were expressed in total liver. FXR-alpha, EAR2, LXR-alpha, HNF4-alpha, and CAR were the most abundantly expressed nuclear receptors in liver parenchymal cells. In contrast, NUR77, COUP-TFII, LXR-alpha/beta, FXR-alpha, and EAR2 were the most highly expressed nuclear receptors in endothelial and Kupffer cells. Interestingly, members of orphan receptor COUP-TF family showed a distinct expression pattern. EAR2 was highly and exclusively expressed in parenchymal cells, while COUP-TFII was moderately and exclusively expressed in endothelial and Kupffer cells. Of interest, the orphan receptor TR4 showed a similar expression pattern as the established lipid sensor PPARgamma. In conclusion, our study provides the most complete quantitative assessment of the NR distribution in liver reported to date. Our gene expression catalog suggests that orphan nuclear receptors such as COUP-TFII, EAR2, and TR4 may be of significant importance as novel targets for pharmaceutical interventions in liver.
  Physiological Genomics 01/2013; · 2.73 Impact Factor
• Source

  Available from: Yanan Wang

  Dataset: 2012 Biochem Pharmacol-Niacin reduces plasma CETP

  Zhaosha Li, Yanan Wang, Ronald J van der Sluis, José W A van der Hoorn, Hans M G Princen, Miranda Van Eck, Theo J C Van Berkel, Patrick C N Rensen, Menno Hoekstra
• Article: Adrenal-Specific Scavenger Receptor BI Deficiency Induces Glucocorticoid Insufficiency and Lowers Plasma Very-Low-Density and Low-Density Lipoprotein Levels in Mice.

  Menno Hoekstra, Ronald J van der Sluis, Miranda Van Eck, Theo J C Van Berkel
  [show abstract] [hide abstract]
  ABSTRACT: OBJECTIVE: We determined the physiological consequences of adrenocortical-specific deletion of scavenger receptor BI (SR-BI) function in C57BL/6 wild-type mice. METHODS AND 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.
  Arteriosclerosis Thrombosis and Vascular Biology 11/2012; · 6.37 Impact Factor
• Article: LCAT deficiency in mice is associated with a diminished adrenal glucocorticoid function.

  Menno Hoekstra, Suzanne J A Korporaal, Ronald J van der Sluis, Veronica Hirsch-Reinshagen, Andrea E Bochem, Cheryl L Wellington, Theo J C Van Berkel, Jan Albert Kuivenhoven, Miranda Van Eck
  [show abstract] [hide abstract]
  ABSTRACT: In vitro studies have suggested that high-density lipoprotein (HDL) and apolipoprotein B-containing lipoproteins can provide cholesterol for synthesis of glucocorticoids. Here we assessed adrenal glucocorticoid function in lecithin-cholesterol acyltransferase (LCAT) knockout mice to determine the specific contribution of HDL-cholesteryl esters to adrenal glucocorticoid output in vivo. LCAT knockout mice exhibit an 8-fold higher plasma free cholesterol-to-cholesteryl ester ratio (P<0.001) and complete HDL-cholesteryl ester deficiency. Apolipoprotein B-containing lipoprotein and associated triglyceride levels are increased in LCAT knockout mice as compared to C57BL/6 controls (+44%; P<0.05). Glucocorticoid producing adrenocortical cells within the zona fasciculata in LCAT knockout mice are devoid of neutral lipids. However, adrenal weights and basal corticosterone levels are not significantly changed in LCAT knockout mice. In contrast, adrenals of LCAT knockout mice show compensatory upregulation of genes involved in cholesterol synthesis (HMGCR; +516%; P<0.001) and acquisition (LDLR; +385%; P<0.001) and a marked 40-50% lower glucocorticoid response to adrenocorticotropic hormone exposure, endotoxemia, or fasting (P<0.001 for all). In conclusion, our studies show that HDL-cholesteryl ester deficiency in LCAT knockout mice is associated with a 40-50% lower adrenal glucocorticoid output. These findings further highlight the important novel role for HDL as cholesterol donor for the synthesis of glucocorticoids by the adrenals.
  The Journal of Lipid Research 11/2012; · 5.56 Impact Factor