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 tumor necrosis factor-α (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.
|Journal||Biochimica et Biophysica Acta - Molecular and Cell Biology of Lipids|
|State||Published - Jun 2021|
Bibliographical noteFunding Information:
This work was funded, in part, by the National Agency for Research and Development (ANID) program Fondo Nacional del Desarrollo Cient?fico y Tecnol?gico (FONDECYT) of Ministry of Science and Technology, Government of Chile, through grants #1150399 (to A.R.), #1180525 (to M.E.A.), #1180347 (to D.B), #11171001 (to D.C.), and #1191145 to (M.A.). This publication also has received funding from grant Millennium Nucleus for Cardiovascular Magnetic Resonance supported by Millennium Science Initiative of the Ministry of Economy, Development and Tourism, Government of Chile and by Comisi?n Nacional de Investigaci?n, Ciencia y Tecnolog?a (CONICYT, AFB170005, CARE Chile UC). Ph.D. Fellowship ANID-PFCHA/Doctorado Nacional/2020-21201346 (to K.R.); and ANID-PCHA/Doctorado Nacional/2016-21160835 (to A.X.). M.F-G was funded by Ministry of Economy, Industry and Competitiveness (MINECO-FEDER; ?Juan de la Cierva? Program IJCI-2016-30025) of Government of Spain. The funding bodies had no role in the design of the study, the collection, analysis, and interpretation of data, or in writing the manuscript.
© 2021 Elsevier B.V.
- Adipose tissue
- Fatty liver
- Lipid metabolism