Effects of Pharmacological Thermogenic Adipocyte Activation on Metabolism and Atherosclerotic Plaque Regression

Figures

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  Figure 1. CL316,243 (CL) treatment reduces adiposity independently of food intake. (A) Study design: low-density lipoprotein receptor (LDLR)-deficient mice were fed a high-fat, high-cholesterol, and high-sucrose-diet (HFCS) for 8 weeks before they were switched to a chow diet supplemented with or without CL316,243 (CL) for 4 weeks; (B) Daily and (C) cumulative food intake (n = 7–9); (D) body weight before (week 0) and after (week 4) intervention with chow or chow + CL; (E) time course of body weight loss; (F) and organ weights after 4 weeks of chow (mock) or chow + CL (CL) feeding in 22 °C housed LDLR-deficient mice.

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  Figure 2. Effects of CL treatment on adipose tissues and liver; (A) representative macroscopic pictures of brown adipose tissue (BAT) and ingWAT (scale bar = 1 cm); (B) representative pictures of H&E-stained sections of BAT (scale bar = 50 µm) and ingWAT (scale bar = 100 µm); (C) relative gene expression normalized to Tbp as housekeeper in ingWAT (n = 7–9); (D) representative pictures of H&E-stained sections of livers (scale bar = 200 µm); (E) liver lipids (n = 7–9), and (F) relative gene expression normalized to Tbp as housekeeper in livers (n = 7–9) of LDLR-deficient mice fed a chow (mock) or chow + CL (CL) diet at 22 °C for 4 weeks.

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  Figure 3. CL treatment reduces plasma lipid levels but does not affect atherosclerosis (A) Plasma cholesterol and triglyceride levels over 4 weeks chow or chow+ CL feeding; and (B) cholesterol and (C) triglyceride levels in fractionized plasma subjected to fast performance liquid chromatography (FPLC) before (d0) and after 4-week chow or chow + CL feeding in LDLR-deficient mice (n = 7–9). (D) Representative pictures of en face stained aortae with (E) corresponding quantification, as well as (F) quantification of lesion area and (G) and lesion severity of aortic roots LDLR-deficient mice fed a chow (mock) or chow + CL (CL) diet at 22 °C for 4 weeks (n = 7–9).