scholarly journals High-density lipoprotein metabolism in human apolipoprotein B100transgenic/brown adipose tissue deficient mice: a model of obesity-induced hyperinsulinemia

2011 ◽  
Vol 36 (3) ◽  
pp. 313-322 ◽  
Author(s):  
Sarah J. Ehlers ◽  
Stephanie M. Larson ◽  
Heather E. Rasmussen ◽  
Young-Ki Park ◽  
Ji-Young Lee
Keyword(s):  
Adipose Tissue ◽  
High Density Lipoprotein ◽  
Brown Adipose Tissue ◽  
Density Lipoprotein ◽  
High Density ◽  
Type I ◽  
Human Apolipoprotein ◽  
Protein Levels ◽  
Brown Adipose ◽  
Hdl Metabolism

Obese and diabetic humans display decreased plasma high-density lipoprotein cholesterol (HDL-C) concentrations and an increased risk for coronary heart disease. However, investigation on HDL metabolism in obesity with a particular emphasis on hepatic ATP-binding cassette transporter A1 (ABCA1), the primary factor for HDL formation, has not been well studied. Human apolipoprotein B100transgenic (hApoBtg) and brown adipose tissue deficient (BATless) mice were crossed to generate hApoBtg/BATless mice. Male and female hApoBtgand hApoBtg/BATless mice were maintained on either a regular rodent chow diet or a diet high in fat and cholesterol until 24 weeks of age. The hApoBtg/BATless mice that were fed a HF/HC diet became obese, developed hepatic steatosis, and had significantly elevated plasma insulin levels compared with their hApoBtgcounterparts, but plasma concentrations of total cholesterol, HDL-C, triglycerides, and free fatty acids and lipoprotein distribution between genotypes were not significantly different. Hepatic expression of genes encoding HDL-modifying factors (e.g., scavenger receptor, class B, type I, hepatic lipase, lecithin:cholesterol acyltransferase, and phospholipid transfer protein) was either altered significantly or showed a trend of difference between 2 genotypes of mice. Importantly, hepatic protein levels of ABCA1 were significantly lowered by ∼35% in male obese hApoBtg/BATless mice with no difference in mRNA levels compared with hApoBtgcounterparts. Despite reduced hepatic ABCA1 protein levels, plasma HDL-C concentrations were not altered in male obese hApoBtg/BATless mice. The result suggests that hepatic ABCA1 may not be a primary contributing factor for perturbations in HDL metabolism in obesity-induced hyperinsulinemia.

Abstract 1392: Increased High Density Lipoprotein Cholesterol induced by Human Apolipoprotein A-I Gene Transfer increases Adiponectin Expression in abdominal Adipose Tissue

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Sophie Van Linthout ◽  
Frank Spillmann ◽  
Anna Foryst-Ludwig ◽  
Carola Bücker-Gärtner ◽  
Marco Meloni ◽  
...  
Keyword(s):  
Gene Transfer ◽  
High Density Lipoprotein ◽  
Plasma Concentrations ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
High Density ◽  
Dependent Manner ◽  
Human Apolipoprotein ◽  
Protein Levels

Introduction: High density lipoprotein (HDL) cholesterol (C) levels positively correlate with plasma adiponectin levels. However, the role of HDL on adiponectin expression is unkown. To investigate the effect of increased HDL levels on adiponectin expression, 1) gene transfer with human apolipoprotein (apo) A-I, the main apo of HDL, was performed in control mice and in lipopolysaccharide (LPS)-injected mice, associated with decreased adiponectin levels and 2) HDL was supplemented in vitro on (pre)-adipocytes. Methods: Eight weeks old male C57BL/6 mice were i.v. injected with 5 × 10e10 total particles of the E1E3E4-deleted adenoviral vector Ad.hapoA-I, expressing human apo A-I or with the same dose of Ad.Null, containing no expression cassette. Fourteen days hereafter, mice were i.p. injected with LPS from Escherichia coli at a dose of 80 mg/kg or with saline. Mice were sacrificed 12 hours after LPS or saline injection. Human apo A-I and mouse adiponectin plasma concentrations were determined by ELISA. Abdominal fat phospho (p) and total (tot.) Akt protein levels were determined by Western Blot; adiponectin mRNA expression of (pre)-adipocytes by real-time PCR. Results: Ad.hapoA-I GT resulted in human apo A-I expression levels of 83Â27>4.6 mg/dl at day 14, which was associated with 1.8-fold (p<0.05) and 1.5-fold (p<0.05) higher HDL-C and adiponectin levels compared to Ad.Null mice, respectively. After LPS-injection, human apo A-I levels decreased by 1.7-fold (p<0.001), leading to 1.7-fold lower adiponectin levels compared to Ad.hapoA-I control mice, but still 1.5-fold (p<0.01) higher compared to LPS-Ad.Null mice. The increased adiponectin levels in Ad.hapoA-I versus Ad.Null LPS-injected mice were associated with a 1.7-fold (p<0.05) increase in p-Akt/tot.Akt ratio. In vitro, LPS administration decreased adiponectin expression by 2.1-fold (p<0.01), which was normalized to control levels by HDL supplementation in a phosphatidylinositol-3-kinase (PI3K)-dependent manner, since Ly 294002 reversed the HDL-mediated increase in adiponectin expression. Conclusion: HDL increases adiponectin expression via the PI3K-Akt pathway, which may contribute to some of the pleiotropic actions of HDL such as its well-known anti-inflammatory effects.

Pcpe2, a Novel Extracellular Matrix Protein, Regulates Adipocyte SR-BI–Mediated High-Density Lipoprotein Uptake

2021 ◽  
Author(s):  
Hao Xu ◽  
Michael J. Thomas ◽  
Sushma Kaul ◽  
Rachel Kallinger ◽  
Amber B. Ouweneel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Density Lipoprotein ◽  
Protein Interactions ◽  
Matrix Protein ◽  
Density Lipoprotein ◽  
Tissue Expansion ◽  
High Density ◽  
Extracellular Matrix Protein ◽  
Tissue Mass ◽  
Brown Adipose

Objective: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)–mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. Approach and Results: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular protein-protein interactions, supporting SR-BI– mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI–mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI–mediated HDL-C uptake is unknown. Differentiated cells from Ldlr −/− / Pcpe2 −/− (Pcpe2 −/− ) and Ldlr −/− (control) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake. SR-BI–mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. Conclusions: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans.

scholarly journals Scavenger Receptor Class B Type I in the Rat Ovary: Possible Role in High Density Lipoprotein Cholesterol Uptake and in the Recognition of Apoptotic Granulosa Cells*

Endocrinology ◽  
1999 ◽  
Vol 140 (6) ◽  
pp. 2494-2500 ◽  
Author(s):  
Per-Arne Svensson ◽  
Magnus S. C. Johnson ◽  
Charlotte Ling ◽  
Lena M. S. Carlsson ◽  
Håkan Billig ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Granulosa Cells ◽  
High Density Lipoprotein Cholesterol ◽  
Scavenger Receptor ◽  
Density Lipoprotein ◽  
High Density ◽  
Lipoprotein Cholesterol ◽  
Type I ◽  
Anionic Phospholipids ◽  
Thecal Cells

Abstract Scavenger receptor class B type I (SR-BI) mediates the selective uptake of high density lipoprotein cholesterol. SR-BI is expressed at high levels in the ovary, indicating that it plays a role in the delivery of cholesterol as substrate for steroid hormone production. However, SR-BI also binds anionic phospholipids with high affinity and could therefore be involved in the recognition of apoptotic cells. In this study we have characterized the expression of SR-BI in rat ovarian follicles undergoing atresia. Atretic follicles with cells undergoing apoptosis were identified by in situ DNA end labeling, and SR-BI expression was determined by in situ hybridization and immunohistochemistry. SR-BI was expressed in thecal cells at all stages of follicular development, including atretic follicles, and in corpus luteum. Isolated apoptotic granulosa cells (but not viable granulosa cells) bound annexin V, indicating that they display anionic phospholipids on the cell surface. Transfection of COS-7 cells with an expression vector carrying the rat SR-BI complementary DNA resulted in increased binding to apoptotic granulosa cells (46 ± 2% of the SR-BI-expressing cells bound at least one granulosa cell compared with 24 ± 3% for the mock-transfected cells; P &lt; 0.0001), whereas the binding to viable granulosa cells was unchanged. Apoptotic granulosa cells also bound to isolated thecal shells. We conclude that thecal cells of both nonatretic and atretic follicles express SR-BI. The location of SR-BI expression in the ovary supports a role of this receptor in the uptake of high density lipoprotein cholesterol. In addition, our data suggest that SR-BI mediates the recognition of apoptotic granulosa cells by the surrounding thecal cells and that it therefore may play a role in the remodeling of atretic follicles to secondary interstitial cells.

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