Article Figures & Data
Figures
- Fig. 1.
High-fat diet effect on body mass composition of Ppargf/f and PpargΔEC mice. Quantitative nuclear magnetic resonance imaging (qNMR) was performed on Ppargf/f and PpargΔEC mice following 12-week treatment on an HFD. Values are presented as a percentage of total body weight.
- Fig. 2.
Rosiglitazone effects on plasma glucose and insulin levels in Ppargf/f and PpargΔEC mice. Plasma glucose (A) and insulin (B) values were determined in Ppargf/f and PpargΔEC mice prior to and following vehicle or rosiglitazone treatment for 14 days, as described in Materials and Methods. Values represent the mean + S.E. *Significantly different compared with respective vehicle controls (P < 0.05).
- Fig. 3.
Histologic analysis of epididymal white adipose tissue from Ppargf/f and PpargΔEC mice. Formalin-fixed, paraffin-embedded samples from each treatment group were assessed as described in Materials and Methods. Vehicle-treated Ppargf/f mice (A), rosiglitazone-treated Ppargf/f mice (B), vehicle-treated PpargΔEC mice (C), and rosiglitazone-treated PpargΔEC mice (D). The bar in the lower right of (D) is 50 μm long. Arrowheads in (A), (C), and (D) indicate single red blood cells in a normal capillary cut in cross section. Short arrows in (A), (C), and (D) point to multiple red blood cells lined up in single file in a normal capillary laying in the plane of the section. Long (concave) arrows in (B) point to abnormally large capillaries observed only in eWAT from rosiglitazone-treated Ppargf/f mice.
- Fig. 4.
Quantitation of enlarged capillaries in epididymal and inguinal white adipose tissue. Epididymal (A) and inguinal (B) adipose tissue were fixed, dehydrated, paraffin embedded, and stained with hematoxylin and eosin. Enlarged capillaries were from 10 widely separated locations of preserved adipocytes, not large blood vessels, lymph nodes, or connective tissue. *Significantly different compared with respective vehicle controls (P < 0.05). VEH, vehicle; ROSI, rosiglitazone.
- Fig. 5.
Role of endothelial PPARγ expression in measures of rosiglitazone-mediated edema. (A) Quantitative nuclear magnetic resonance imaging was performed on Ppargf/f and PpargΔEC mice following vehicle (VEH) or rosiglitazone (ROSI) treatment as described earlier. Values represent absolute fluid mass in milliliters. (B) Extracellular fluid volume in Ppargf/f and PpargΔEC mice following vehicle or rosiglitazone treatment as determined by bioimpedance measurements. (C) Plasma volume (PV) in Ppargf/f and PpargΔEC mice following vehicle or rosiglitazone treatment as determined by the Evan’s blue assay. All values are reported as the mean + S.E. *Significantly different compared with respective vehicle controls (P < 0.05).
- Fig. 6.
Tissue water content in vehicle (VEH)- or rosiglitazone (ROSI)-treated Ppargf/f and PpargΔEC mice. Water content in epididymal (A), inguinal (B), and retroperitoneal white adipose tissue (rWAT) (C) and skeletal muscle (D) in VEH- or ROSI-treated Ppargf/f and PpargΔEC mice was assessed following tissue collection at necropsy. The difference between wet tissue weight and dry tissue weight following lyophilization (reflecting absolute water weight) was normalized to wet tissue weight prior to lyophilization. All values are reported as the mean + S.E. *Significantly different compared with respective vehicle controls (P < 0.05).
- Fig. 7.
Endothelial expression changes in vehicle- or rosiglitazone-treated Ppargf/f and PpargΔEC mice. (A and B) Analysis of Pparg and Fak mRNAs within isolated lung ECs from (n = 3) untreated Ppargf/f and PpargΔEC mice. All values are calculated relative to the internal control glyceraldehyde-3-phosphate dehydrogenase (GAPDH) mRNA, and reported as a mean percentage + S.D. of mRNA expression in Ppargf/f mice. (C–E) Immunofluorescent evaluation of VE-cadherin in EC junctions from lung samples of (n = 3) Ppargf/f and PpargΔEC mice. Samples were stained with 4′,6-diamidino-2-phenylindole (blue), PECAM (green), and VE-cadherin (red). (C) Representative image from Ppargf/f lung sample. (D) Representative image from PpargΔEC lung sample. (E) Integrated intensity of VE-cadherin expression in EC junctions of Ppargf/f and PpargΔEC mice. *Significantly different compared with controls (P < 0.05).
- Fig. 8.
Summary model of PPARγ-dependent edema mechanism. Left panel, Rosiglitazone (ROSI)-mediated activation of PPARγ signaling in ECs suppresses FAK, leading to direct or indirect decreases in VE-cadherin expression and EC adherens junctions, allowing for increased edema. Right panel, Loss of PPARγ expression/signaling abrogates FAK repression and enhances VE-cadherin expression and adherens junctions between ECs, thereby minimizing edema.
Additional Files
Data Supplement
- Supplemental Figure -
S1: Body and select tissues weights from Ppargf/f and PpargDeltaEC mice.
- Supplemental Figure -
