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

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

Research output: Contribution to journalArticlepeer-review

Abstract

Scavenger receptor class B type 1 (SR-B1) is a membrane lipoprotein receptor/lipid transporter involved in the pathogenesis of atherosclerosis, but its role in obesity and fatty liver development is unclear. Here, we determined the effects of SR-B1 deficiency on plasma metabolic and inflammatory parameters as well as fat deposition in adipose tissue and liver during obesity. To induce obesity, we performed high-fat diet (HFD) exposure for 12 weeks in male SR-B1 knock-out (SR-B1-/-, n = 14) and wild-type (WT, n = 12) mice. Compared to HFD-fed WT mice, plasma from HFD-fed SR-B1-/- animals exhibited increased total cholesterol, triglycerides (TG) and TNF-α levels. In addition, hypertrophied adipocytes and macrophage-containing crown-like structures (CLS) were observed in adipose tissue from HFD-fed SR-B1 deficient mice. Remarkably, liver from obese SR-B1-/- mice showed attenuated TG content, dysregulation in hepatic peroxisome proliferator-activated receptors (PPARs) expression, increased hepatic TG secretion, and altered hepatic fatty acid (FA) composition. In conclusion, we show that SR-B1 deficiency alters the metabolic environment of obese mice through modulation of liver and adipose tissue lipid accumulation. Our findings provide the basis for further elucidation of SR-B1's role in obesity and fatty liver, two major public health issues that increase the risk of advanced chronic diseases and overall mortality.

Original languageEnglish
Article number158909
Pages (from-to)158909
JournalBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids
Volume1866
Issue number6
Early online date22 Feb 2021
DOIs
StateE-pub ahead of print - 22 Feb 2021

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