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

• Published in: Biochimica et biophysica acta. Molecular and cell biology of lipids Vol. 1866; no. 6; p. 158909
• Main Authors: Rivera, Katherine, Quiñones, Verónica, Amigo, Ludwig, Santander, Nicolás, Salas-Pérez, Francisca, Xavier, Aline, Fernández-Galilea, Marta, Carrasco, Gonzalo, Cabrera, Daniel, Arrese, Marco, Busso, Dolores, Andia, Marcelo E., Rigotti, Attilio
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2021
• Subjects: Adipose tissue; Adipose Tissue - metabolism; Adipose Tissue - pathology; Animals; Diet, High-Fat - adverse effects; Fatty liver; Fatty Liver - etiology; Fatty Liver - genetics; Fatty Liver - metabolism; Fatty Liver - pathology; Inflammation - metabolism; Inflammation - pathology; Lipid metabolism; Liver - metabolism; Liver - pathology; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Obesity; Obesity - etiology; Obesity - genetics; Obesity - metabolism; Obesity - pathology; Scavenger Receptors, Class B - deficiency; Scavenger Receptors, Class B - genetics; Scavenger Receptors, Class B - metabolism; SR-B1; Triglycerides - metabolism; FFA; Adipose tissue; HFD; ALT; Mgat1; CLS; Srebp1c; AUC; HDL-C; RT-PCR; VLDL; Scd1; Lipid metabolism; Obesity; PUFA; H&E; Mttp; IR; Cpt1; Gapdh; PPARα; IL-10; PPARγ; CVD; HOMA-IR; Dgat2; Ldlr; FA; ELISA; NAFLD; RCT; Lrp1; MUFA; LPL; WAT; SFA; HDL; S1P; Fatty liver; LDL; Fasn; WT; BMI; FPLC; GC–MS; eWAT; SR-B1; NASH; MAFLD; TG; TNF-α; ApoA-I; GGT; Apob
• ISSN: 1388-1981; 1879-2618; 1879-2618
• DOI: 10.1016/j.bbalip.2021.158909

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. •SR-B1 modulates HDL metabolism and atherosclerosis, but its role in fat accumulation during obesity is not well defined.•Absence of SR-B1 promotes inflammatory hypertrophy of white fat cells and decreases hepatic steatosis in obese mice.•Obese SR-B1-deficient mice exhibit lipid metabolism-related consistent with reduced liver triglycerides.•Livers of obese SR-B1-deficient obese mice show changes in fatty acid composition and increased triglyceride secretion.