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. 2014 Dec 4;159(6):1404–1416. doi: 10.1016/j.cell.2014.10.058

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© 2014 The Authors

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).

PMC Copyright notice

Leptin Signaling Is Required for the Obesity-Induced Increases in BP

(A) Body weight (g) of mice fed 20 weeks a high-calorie (DIO, ob/ob, and db/db mice) or chow (lean ob/ob and db/db mice) diet ad libitum, ^∗∗∗p < 0.001 versus lean, ⁺⁺⁺p < 0.001 versus ob/ob HFD fed, ###p < 0.001 versus db/db HFD (lean, n = 14; DIO, n = 37; ob/ob, n = 8; db/db, n = 3; ob/ob, HFD = 3; db/db, HFD = 5).

(B) Average heart rate (BPM) over a 24 hr period of mice fed a high-calorie (DIO mice) or chow (lean mice) diet, ob/ob mice and db/db mice fed a chow diet for over 20 weeks (lean, n = 14; DIO, n = 37; ob/ob, n = 8; db/db, n = 3; ob/ob, HFD = 3; db/db, HFD = 5).

(C) Heart rate (BPM) over a 24 hr period in mice fed a chow diet (lean mice), HFD-fed DIO mice, chow-fed ob/ob and db/db mice, and HFD-fed ob/ob and db/db mice. Measurements at 20 weeks are presented (lean, n = 14; DIO, n = 37; ob/ob, n = 8; db/db, n = 3; ob/ob, HFD = 3; db/db, HFD = 5).

(D) Average SBP (mmHg) over a 24 hr period of mice fed a high-calorie (DIO mice) or chow (lean mice) diet, ob/ob mice and db/db mice fed a chow diet for 20 weeks (lean, n = 14; DIO, n = 37; ob/ob, n = 8; db/db, n = 3; ob/ob, HFD = 3; db/db, HFD = 5).

(E) SBP (mmHg) over a 24 hr period in mice fed a chow diet (lean mice), HFD-fed DIO mice, chow-fed ob/ob and db/db mice, and HFD-fed ob/ob and db/db mice for 20 weeks (lean, n = 14; DIO, n = 37; ob/ob, n = 8; db/db, n = 3; ob/ob, HFD = 3; db/db, HFD = 5).

(F) Average DBP (mmHg) over a 24 hr period of mice fed a high-calorie (DIO mice) or chow (lean mice) diet, ob/ob mice and db/db mice fed a chow diet for 20 weeks (lean, n = 14; DIO, n = 37; ob/ob, n = 8; db/db, n = 3; ob/ob, HFD = 3; db/db, HFD = 5).

(G) DBP (mmHg) over a 24 hr period in mice fed a chow diet (lean mice), HFD-fed DIO mice, chow-fed ob/ob and db/db mice, and HFD-fed ob/ob and db/db mice (lean, n = 14; DIO, n = 37; ob/ob, n = 8; db/db, n = 3; ob/ob, HFD = 3; db/db, HFD = 5).

(H) Plasma leptin (ng/ml) correlates with heart rate (BPM). Linear regression, r² = 0.5855; p < 0.001; n = 24.

(I) Plasma leptin (ng/ml) correlates with SBP (mmHg). Linear regression, r² = 0.6205; p < 0.001; n = 24.

(J) Plasma leptin (ng/ml) correlates with DBP. Linear regression, r² = 0.5883; p < 0.001; n = 24.

(K) Exogenous leptin administration into ob/ob mice increased heart rate. Vehicle (Veh) treatment into ob/ob mice and leptin administration into db/db mice produced no change. Two-way ANOVA, Bonferroni post hoc test. n = 3–8.

(L) Average heart rate (BPM) over 11 day treatment period of leptin-treated ob/ob mice, compared to the baseline HR of ob/ob mice, the baseline of DIO and lean mice. One-way ANOVA, Bonferroni post hoc test, paired t test between leptin-treated ob/ob mice and ob/ob baseline, n = 8–37.

(M) Exogenous leptin administration into ob/ob mice, increased SBP (mmHg). Vehicle treatment into ob/ob mice and leptin administration into db/db mice produced no change. Values represent mean ± SEM. Two-way ANOVA, Bonferroni post hoc test. n = 3–8.

(N) Average SBP (mmHg) over 11 day treatment period of leptin-treated ob/ob mice compared to ob/ob baseline SBP, DIO, and lean baseline SBP measurements. One-way ANOVA, Bonferroni post hoc test, paired t test between leptin-treated ob/ob mice and ob/ob baseline. n = 8–37.

(O) Exogenous leptin administration into ob/ob mice increased diastolic BP (DBP) (mmHg). Vehicle treatment into ob/ob mice and leptin administration into db/db mice produced no change. Two-way ANOVA, Bonferroni post hoc test. n = 3–8.

(P) Average DBP (mmHg) over 11 day treatment period of leptin-treated ob/ob mice compared to ob/ob baseline DBP, DIO baseline DBP, and lean mice DBP. One-way ANOVA, paired t test between leptin-treated ob/ob mice and ob/ob baseline. n = 8–37.

Values represent mean ± SEM, one-way AVOVA, Bonferroni post hoc test, unless specifically stated. ^∗p < 0.05, ^∗∗p < 0.01, and ^∗∗∗p < 0.001. See also Figure S1.