Lipoprotein receptor SR-B1 deficiency enhances adipose tissue inflammation and reduces susceptibility to hepatic steatosis during diet-induced obesity in mice

Rivera, Katherine; Quiñones, Verónica; Amigo, Ludwig; Santander, Nicolás; Salas-Pérez, Francisca; Xavier, Aline; Fernández‐Galilea, Marta; Carrasco, Gonzalo; Cabrera, Daniel; Arrese, Marco; Busso, Dolores; Andía, Marcelo E.; Rigotti, Attilio

doi:10.1016/j.bbalip.2021.158909

Cited by 6 publications

(5 citation statements)

References 63 publications

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“…Together, the increased rate of glucose clearance with SR-BI deficiency may be due to increased glucose uptake in adipose tissue, thereby predisposing SR-BI -/mice to obesity. On the contrary, another study found that loss of SR-BI in mice did not lead to increased weight gain compared to HFD-fed WT mice, although it was observed that SR-BI -/mice had hypertrophied adipocytes 34 . It is possible that glucose clearance in SR-BI -/mice is (which was not certified by peer review) is the author/funder.…”

Section: Discussionmentioning

confidence: 92%

Scavenger receptor class B type I is required for efficient glucose uptake and metabolic homeostasis in adipocytes

Knaack,

Chang,

Thomas

et al. 2023

Preprint

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Obesity is a worldwide epidemic and places individuals at a higher risk for developing comorbidities that include cardiovascular disease and type 2 diabetes. Adipose tissue contains adipocytes that are responsible for lipid metabolism and reducing misdirected lipid storage. Adipocytes facilitate this process through insulin-mediated uptake of glucose and its subsequent metabolism into triglycerides for storage. During obesity, adipocytes become insulin resistant and have a reduced ability to mediate glucose import, thus resulting in whole-body metabolic dysfunction. Scavenger receptor class B type I (SR-BI) has been implicated in glucose uptake in skeletal muscle and adipocytes via its native ligands, apolipoprotein A-1 and high-density lipoproteins. Further, SR-BI translocation to the cell surface in adipocytes is sensitive to insulin stimulation. Using adipocytes differentiated from ear mesenchymal stem cells isolated from wild-type and SR-BI knockout (SR-BI-/-) mice as our model system, we tested the hypothesis that SR-BI is required for insulin-mediated glucose uptake and regulation of energy balance in adipocytes. We demonstrated that loss of SR-BI in adipocytes resulted in inefficient glucose uptake regardless of cell surface expression levels of glucose transporter 4 compared to WT adipocytes. We also observed reduced glycolytic capacity, increased lipid biosynthesis, and dysregulated expression of lipid metabolism genes in SR-BI-/-adipocytes compared to WT adipocytes. These results partially support our hypothesis and suggest a novel role for SR-BI in glucose uptake and metabolic homeostasis in adipocytes.

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Section: Discussionmentioning

confidence: 92%

Scavenger receptor class B type I is required for efficient glucose uptake and metabolic homeostasis in adipocytes

Knaack,

Chang,

Thomas

et al. 2023

Preprint

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“… 55 SRB1 is another multiligand membrane receptor protein whose primary role is to control selective cholesterol trafficking. 56 SRB-1 mediates both the influx of HDL-derived cholesteryl esters into cells and tissues by reverse cholesterol transport and efflux of cholesterol from peripheral tissues, including macrophage foam cells, back to the liver for bile acid formation, with subsequent biliary secretion or transport to steroidogenic tissues, particularly the adrenal gland and ovary, for steroid synthesis and storage. Therefore, upregulation of the SRB1 levels in the visceral fat tissues and downregulation in the liver lower the plasma lipid levels.…”

Section: Discussionmentioning

confidence: 99%

“…Atheroprotective effects of APOE include its role in cholesterol efflux, suppression of smooth muscle cell proliferation, protection against lipid peroxidation, and limitation of platelet aggregation through interacting with several receptors including LDL receptor-related protein 1 (LRP1), the VLDL receptors, and the ApoE2 receptor . SRB1 is another multiligand membrane receptor protein whose primary role is to control selective cholesterol trafficking . SRB-1 mediates both the influx of HDL-derived cholesteryl esters into cells and tissues by reverse cholesterol transport and efflux of cholesterol from peripheral tissues, including macrophage foam cells, back to the liver for bile acid formation, with subsequent biliary secretion or transport to steroidogenic tissues, particularly the adrenal gland and ovary, for steroid synthesis and storage.…”

Section: Discussionmentioning

confidence: 99%

Imine Derivatives of Benzoxazole Attenuate High-Fat Diet-Induced Hyperlipidemia by Modulation of Lipid-Regulating Genes

et al. 2023

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Purpose: Hyperlipidemia being the prominent risk factor of cardiovascular diseases and side effects associated with the current lipid-lowering drugs have attracted the interest of scientists in the quest for new alternatives. In view of the diverse pharmacological potentials of benzoxazole (BZX) compounds, this study was designed to evaluate the antihyperlipidemic activity of imine derivatives of BZX in high-fat diet (HFD)-fed rats. Methods: Hyperlipidemia was induced in Sprague–Dawley rats by using HFD for 28 days. On the 28th day, blood samples were collected, and animals having serum triglycerides (TG) greater than 400 mg/dL and total cholesterol (TC) greater than 280 mg/dL were selected for further study. Hyperlipidemic rats were daily treated with either a vehicle or simvastatin (SIM; 20 mg/kg) or BZX compounds (10, 20, and 30 mg/kg), for 12 consecutive days. After the specified time duration, hyperlipidemic biomarkers were evaluated in the blood samples of sacrificed rats. Liver samples were collected for histopathological and mRNA analyses. Binding affinities of BZX derivatives with different targets were assessed by molecular docking. Results: The present study revealed that the BZX derivatives dose-dependently reduced the serum levels of TC, TG, low-density lipoprotein, and very low-density lipoprotein along with improvement in high-density lipoprotein levels. Similarly, all the compounds reduced HFD-induced alanine transaminase and aspartate aminotransferase levels except BZX-4. Histopathology of liver samples demonstrated mild to moderate fatty changes upon treatment with BZX-1, BZX-2, and BZX-4. The hepatic architecture of the BZX-3-treated samples was close to normal, and only mild inflammation was witnessed in these samples. Moreover, all the compounds significantly increased superoxide dismutase and glutathione levels, indicating their antioxidant potentials. Gene expression data showed that BZX-1 and BZX-3 reduced lipid levels by inhibiting HMGCR, APOB, PCSK9, SRB1, and VCAM1 and via improving PPAR-α and APOE mRNA levels. BZX-2 demonstrated its antihyperlipidemic effects mainly due to inhibition of APOB, while BZX-4-mediated effects appeared to be due to attenuation of APOB, PCSK9, and SRB1. BZX derivatives displayed strong binding affinities with HMGCR, APOB, and VCAM1, which suggested that some of the interactions might be required for inhibition of these target proteins. Conclusions: Based on the current findings, it can be concluded that BZX derivatives exert their antihyperlipidemic effects via modulation of multiple lipid-regulating genes.

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“…In addition to modified and unmodified LDLs, other lipids such as cholesterols and phospholipids, bacterial pathogens, oxidative particles, and apoptotic cells are all scavenged by macrophages via these scavenger receptors ( 155 ). In NASH induced by feeding of Western diet, deletion of macrophage scavenger receptor MSR or type B1 scavenger receptor CD-36 led to reduced inflammation likely due to their effects on intracellular cholesterol trafficking in Kupffer cells ( 162 , 163 ). In LDL receptor deficient (ldl4-/-) mice fed HFD, loss of CD36 or MSR resulted in reduced hepatic inflammation ( 162 ).…”

Section: Macrophage Reprogramming In Steatosis Driven Hccmentioning

confidence: 99%

Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis

Alba

Datta

et al. 2022

Front. Oncol.

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Obesity confers an independent risk for carcinogenesis. Classically viewed as a genetic disease, owing to the discovery of tumor suppressors and oncogenes, genetic events alone are not sufficient to explain the progression and development of cancers. Tumor development is often associated with metabolic and immunological changes. In particular, obesity is found to significantly increase the mortality rate of liver cancer. As its role is not defined, a fundamental question is whether and how metabolic changes drive the development of cancer. In this review, we will dissect the current literature demonstrating that liver lipid dysfunction is a critical component driving the progression of cancer. We will discuss the involvement of inflammation in lipid dysfunction driven liver cancer development with a focus on the involvement of liver macrophages. We will first discuss the association of steatosis with liver cancer. This will be followed with a literature summary demonstrating the importance of inflammation and particularly macrophages in the progression of liver steatosis and highlighting the evidence that macrophages and macrophage produced inflammatory mediators are critical for liver cancer development. We will then discuss the specific inflammatory mediators and their roles in steatosis driven liver cancer development. Finally, we will summarize the molecular pattern (PAMP and DAMP) as well as lipid particle signals that are involved in the activation, infiltration and reprogramming of liver macrophages. We will also discuss some of the therapies that may interfere with lipid metabolism and also affect liver cancer development.

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Lipoprotein receptor SR-B1 deficiency enhances adipose tissue inflammation and reduces susceptibility to hepatic steatosis during diet-induced obesity in mice

Cited by 6 publications

References 63 publications

Scavenger receptor class B type I is required for efficient glucose uptake and metabolic homeostasis in adipocytes

Scavenger receptor class B type I is required for efficient glucose uptake and metabolic homeostasis in adipocytes

Imine Derivatives of Benzoxazole Attenuate High-Fat Diet-Induced Hyperlipidemia by Modulation of Lipid-Regulating Genes

Hepatic macrophage mediated immune response in liver steatosis driven carcinogenesis

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