Overexpression of sterol carrier protein-2 differentially alters hepatic cholesterol accumulation in cholesterol-fed mice

Barbara P. Atshaves; Avery L. McIntosh; Gregory G. Martin; Danilo Landrock; H. Ross Payne; Shivaprasad Bhuvanendran; Kerstin K. Landrock; Olga I. Lyuksyutova; Jeffery D. Johnson; Ronald D. Macfarlane; Ann B. Kier; Friedhelm Schroeder

Journal of Lipid Research (Jul 2009)

Overexpression of sterol carrier protein-2 differentially alters hepatic cholesterol accumulation in cholesterol-fed mice

Barbara P. Atshaves,
Avery L. McIntosh,
Gregory G. Martin,
Danilo Landrock,
H. Ross Payne,
Shivaprasad Bhuvanendran,
Kerstin K. Landrock,
Olga I. Lyuksyutova,
Jeffery D. Johnson,
Ronald D. Macfarlane,
Ann B. Kier,
Friedhelm Schroeder

Affiliations

Barbara P. Atshaves: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Avery L. McIntosh: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Gregory G. Martin: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Danilo Landrock: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
H. Ross Payne: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Shivaprasad Bhuvanendran: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Kerstin K. Landrock: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Olga I. Lyuksyutova: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Jeffery D. Johnson: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Ronald D. Macfarlane: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Ann B. Kier: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466
Friedhelm Schroeder: Department of Physiology and Pharmacology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Pathobiology, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466; Department of Chemistry, Texas A&M University, Texas Veterinary Medical Center, College Station, TX 77843-4466

Journal volume & issue: Vol. 50, no. 7
pp. 1429 – 1447

Abstract

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Although in vitro studies suggest a role for sterol carrier protein-2 (SCP-2) in cholesterol trafficking and metabolism, the physiological significance of these observations remains unclear. This issue was addressed by examining the response of mice overexpressing physiologically relevant levels of SCP-2 to a cholesterol-rich diet. While neither SCP-2 overexpression nor cholesterol-rich diet altered food consumption, increased weight gain, hepatic lipid, and bile acid accumulation were observed in wild-type mice fed the cholesterol-rich diet. SCP-2 overexpression further exacerbated hepatic lipid accumulation in cholesterol-fed females (cholesterol/cholesteryl esters) and males (cholesterol/cholesteryl esters and triacyglycerol). Primarily in female mice, hepatic cholesterol accumulation induced by SCP-2 overexpression was associated with increased levels of LDL-receptor, HDL-receptor scavenger receptor-B1 (SR-B1) (as well as PDZK1 and/or membrane-associated protein 17 kDa), SCP-2, liver fatty acid binding protein (L-FABP), and 3α-hydroxysteroid dehydrogenase, without alteration of other proteins involved in cholesterol uptake (caveolin), esterification (ACAT2), efflux (ATP binding cassette A-1 receptor, ABCG5/8, and apolipoprotein A1), or oxidation/transport of bile salts (cholesterol 7α-hydroxylase, sterol 27α-hydroxylase, Na+/taurocholate cotransporter, Oatp1a1, and Oatp1a4). The effects of SCP-2 overexpression and cholesterol-rich diet was downregulation of proteins involved in cholesterol transport (L-FABP and SR-B1), cholesterol synthesis (related to sterol regulatory element binding protein 2 and HMG-CoA reductase), and bile acid oxidation/transport (via Oapt1a1, Oatp1a4, and SCP-x). Levels of serum and hepatic bile acids were decreased in cholesterol-fed SCP-2 overexpression mice, especially in females, while the total bile acid pool was minimally affected. Taken together, these findings support an important role for SCP-2 in hepatic cholesterol homeostasis.

Published in Journal of Lipid Research

ISSN: 0022-2275 (Print); 1539-7262 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science: Chemistry: Organic chemistry: Biochemistry
Website: https://www.journals.elsevier.com/journal-of-lipid-research

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