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Comparative Study
. 2010 Jul;28(7):1466-70.
doi: 10.1097/HJH.0b013e328339f20e.

Enhanced blood pressure and appetite responses to chronic central melanocortin-3/4 receptor blockade in dietary-induced obesity

John H Dubinion  1 , Alexandre A da Silva, John E Hall
Affiliations
Comparative Study

Enhanced blood pressure and appetite responses to chronic central melanocortin-3/4 receptor blockade in dietary-induced obesity

John H Dubinion et al. J Hypertens. 2010 Jul.

Abstract

Method: We examined the role of central nervous system (CNS) endogenous melanocortin 3/4 receptors (MC3/4R) activity in controlling cardiovascular and metabolic functions in Sprague Dawley rats fed a high-fat diet (n = 6) for 10 months compared with rats fed a standard chow (normal fat, n = 8) starting at 3 weeks of age.

Results: At 7 months of age, high-fat rats were heavier (473 +/- 3 vs. 424 +/- 7 g), consumed more calories with larger, less frequent meals and had reduced respiratory quotient (RQ) compared with normal-fat rats. After 10 months on the diets, arterial and venous catheters were implanted for measurement of mean arterial pressure (MAP) and heart rate (HR) 24-h/day and i.v. (intravenous) infusions, and a 21G steel cannula was placed in the lateral ventricle for intracerebroventricular (ICV) infusions. High-fat rats were heavier (528 +/- 14 vs. 477 +/- 11 g) with increased visceral adiposity and significantly higher MAP (108 +/- 3 vs. 102 +/- 1 mmHg). After a 5-day control period, the rats were infused with a MC3/4R antagonist (SHU-9119, 1 nmol/h, ICV) for 10 days followed by a 5-day recovery period. SHU-9119 infusion for 10 days increased caloric intake significantly more in high-fat rats (159 +/- 19 vs. 64 +/- 8 kcal). Despite increasing caloric intake and rapid weight gain, MC3/4R antagonism reduced MAP more in high-fat diet compared with normal-fat rats (-7.9 +/- 0.3 vs. -4.7 +/- 1.3 mmHg, average reduction of last 4 days of blockade).

Conclusion: These observations suggest that a high-fat diet increases endogenous activity of the CNS MC3/4R and that an intact MC3/4 appears to play an important role in linking increased blood pressure with diet-induced obesity.

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Conflict of interest statement

Conflict of interest: none

Figures

Figure 1
Figure 1
Effects of chronic ICV administration of the MC3/4R antagonist, SHU-9119 (1 nmol/hr) on caloric intake in SD rats fed a NF (n=8) or HF (n=6) diet for 10 months.
Figure 2
Figure 2
Effects of chronic ICV administration of the MC3/4R antagonist, SHU-9119 (1 nmol/hr), on (A) MAP, (B) change in MAP, and (C) HR in SD rats fed a NF (n=8) or HF (n=6) diet for 10 months.
Figure 2
Figure 2
Effects of chronic ICV administration of the MC3/4R antagonist, SHU-9119 (1 nmol/hr), on (A) MAP, (B) change in MAP, and (C) HR in SD rats fed a NF (n=8) or HF (n=6) diet for 10 months.
See this image and copyright information in PMC

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