Figure 1.
Body weight at commencement of the study (top left panel) and at the end of 20 week diet protocol (top right panel), and 24 hr food intake (bottom left panel) and 24 hr caloric intake (bottom right) in wildtype (WT; open bars) and GDNF HET (hatched bars) mice fed control (CONT) or high fat (HFF) diet.
Data analyzed by two way ANOVA with the factors of genotype (gp), diet and interaction (int; diet x genotype). Values are mean ± SEM. n = WT-CONT 12, -HFF 13; HET-CONT 11, -HFF 8.
Figure 2.
Mean arterial pressure (MAP; top panels), heart rate (middle panels) and locomotor activity (bottom panels) for 24hour period (left panels), night time (center) and day time (right panels) in wildtype (WT; open bars) and GDNF HET (hatched bars) mice fed control (CONT) or high fat (HFF) diet.
Data analyzed by two way ANOVA with the factors of genotype (gp), diet and interaction (int; diet x genotype). *P<0.05 using Bonferonni post hoc analysis Values are mean ± SEM. n = WT-CONT 9, -HFF 8; HET-CONT 7, -HFF 5.
Figure 3.
24hour urine production, creatinine clearance and 24 hr albumin excretion of wildtype (WT; open bars) and GDNF HET (hatched bars) mice fed control (CONT) or high fat (HFF) diet.
Parameters are expressed in absolute (top panels) values and values adjusted for bodyweight (lower panels). Data analyzed by two way ANOVA with the factors of genotype (gp), diet and interaction (int; diet x genotype). Values are mean ± SEM. n = 7–13 per group.
Table 1.
Terminal Tissue and Plasma Profile.
Figure 4.
Typical histological features of kidneys of wildtype (WT) and GDNF HET mice fed control (CONT) or high fat (HFF) diet.
Panels A-F: High power images of typical glomeruli stained with periodic acid-Schiff (PAS). Glomeruli of WT-CONT (A) and HET-CONT (B) appeared normal with no differences in PAS positive staining. Glomeruli of WT-HFF mice showed glomerular hypertrophy (C) and some presented with glomerulosclerosis (D). Kidneys of HET-HFF mice contained very large glomeruli (E) and glomeruli with glomerulosclerosis (F). Bar = 100 um. Panels G-J: Fluorescent micrographs of collagen IV (Red) immunostaining. Collagen IV immunostaining in control WT (G) and HET (H) kidneys presented as a fine matrix localized to basement membranes of renal tubules, Bowmans capsule and the intra and extraglomerular mesangium. In obese WT (I) and HET (J) kidneys, the accumulation of collagen IV protein was present and localized to the tubulointerstitium associated with expansion of the interstitial space (arrow). More extensive collagen IV was also evident in the glomerulointerstitium surrounding the glomerular Bowman’s capsule.
Figure 5.
Panel A: Renal collagen concentration (collagen content expressed as percentage of dry tissue weight) of wildtype (WT; open bars; n = 8) and GDNF HET (hatched bars; n = 6) mice fed control (CONT) or high fat (HFF) diet. Panel B: SDS-PAGE acrylamide gel. Panel C and D: Densitometry of collagen I and collagen V subtypes with values expressed relative to control WT (n = 6/group). Data analyzed by two way ANOVA with the factors of genotype (gp), diet and interaction (int). *P<0.01 using Bonferonni post hoc analysis Values are mean ± SEM.