Obesity Human Soluble Prorenin Receptor Expressed in Adipose Tissue Improves Insulin Sensitivity and Endothelial Function in Obese Female Mice

Figure 1. Generation and validation of adipose-specific human sPRR (Adi-HsPRR) mouse model. (A) Adipose tissue-derived human sPRR male and female mice were generated by breeding heterozygote male mice that expressed Cre recombinase under the control of the Adiponectin promoter with female heterozygote mice that expressed the human soluble prorenin receptor (HsPRR/+). (B) Expression of Human sPRR was validated by the detection of myc-tagged HsPRR in adipose tissue (peri-renal, gonadal, and subcutaneous). Tissue sPRR expression was assessed via western blot in (C) Male and (D) Female mice. Data are expressed as mean ± SEM of 7–1 mice/group. A 2-way ANOVA was performed to detect differences

Figure 2. Effect of Adi-HsPRR expression of Adipose Tissue Fat pads at takedown in (A) Male and (B) Female mice. Data are expressed as mean ± SEM of 8–16 mice/group. A 3-way ANOVA was performed to detect differences. Tissue morphology of gonadal white adipose tissue was analyzed and quantified in (C) Male HFD and (D) Female HFD mice using Nikon NIS Elements BR.3.10 software at 10X (200μm). Data are expressed as mean ± SEM of 5–15 mice/group. Gene expression analysis was performed in gonadal WAT of (E) Male HFD and (F) Female HFD mice. Data are expressed as mean ± SEM of 8–15 mice/group. A t-test was performed to detect differences.

Figure 3. Adi-HsPRR expression modulates circulating RAS Plasma sPRR in (A) Male and (B) Female mice. Data are expressed as mean ± SEM of 7–17 mice/group. Plasma renin in (C) Male and (D) Female mice. Data are expressed as mean ± SEM of 5–11 mice/group. Plasma Ang 1–7 in (E) Male and (F) Female mice. Data are expressed as mean ± SEM of 4 mice/group. A 2-way ANOVA was performed to detect differences

Figure 4. Increased plasma sPRR correlates with adiposity in obese females Linear regression of visceral adiposity (gWAT) and plasma sPRR in (A) Male mice, and (B) Female mice. A simple linear regression was performed to detect differences.

Figure 5. Adi-HsPRR improves insulin sensitivity in HFD females. Time-dependent glycemia and area under the curve after glucose injection in (A) Male and (B) Female mice. Data are expressed as mean ± SEM of 9–14 mice/group. Time-dependent glycemia and area under the curve after insulin injection in (C) Male and (D) Female mice. Data are expressed as mean ± SEM of 6–13 mice/group. A 2-way ANOVA was performed to detect differences.

Figure 6. Adi-HsPRR improves endothelium-dependent vascular relaxation in HFD females. Vascular relaxation in (A) Male and (B) Female mice. Data are expressed as mean ± SEM of 5 mice/group. A 2-way repeat ANOVA was performed to detect differences. Day and night systolic blood pressure in (A) Male and (B) Female mice. Data are expressed as mean ± SEM of 4–9 mice/group. A 3-way repeat ANOVA was performed to detect differences.