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Review
. 2009 Dec 1;120(22):2260-8.
doi: 10.1161/CIRCULATIONAHA.109.854612.

Science of self-preservation: how melanocortin action in the brain modulates body weight, blood pressure, and ischemic damage

Marcus P Corander  1 , Matthew Fenech, Anthony P Coll
Affiliations
Review

Science of self-preservation: how melanocortin action in the brain modulates body weight, blood pressure, and ischemic damage

Marcus P Corander et al. Circulation. .
No abstract available

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Figures

Figure 1
Figure 1
POMC is a precursor peptide. Cleavage of this large prohormone by the action of prohormone convertases at basic amino acid cleavage sites (dotted) produces a range of smaller peptides, including the melanocortins (highlighted). α-MSH is encoded entirely within ACTH. Abbreviations: POMC, pro-opiomelanocortin; NT, N-terminal fragment; JP, joining peptide; ACTH, adrenocorticotropic hormone; β-, γ-LPH, β-, γ-lipotropin; α-, β-, γ-MSH, α-, β-, γ-melanocyte stimulating hormone; β-END, β-endorphin.
Figure 2
Figure 2
The leptin-melanocortin system and energy homeostasis. The arcuate nucleus within the hypothalamus has a critical role in integrating circulating nutritional-dependent signals from the periphery and thereby communicating energy balance status to the central nervous system. The adipose-derived cytokine leptin is produced in proportion to fat cell mass, increasing with overfeeding and decreasing with starvation. Acting via receptors expressed on POMC and AgRP neurons within the hypothalamus, leptin can modulate central melanocortin tone to effect changes in food intake and energy expenditure. Abbreviations: ObRb, leptin receptor; POMC, pro-opiomelanocortin; AgRP, agouti-related protein; ARC, arcuate nucleus; PVN, paraventricular nucleus; MC4-R, melanocortin 4 receptor.
Figure 3
Figure 3
Basal 24-hour average mean arterial pressure and heart rate in male 17- to 19-week-old MC4-R (−/−), MC4-R (+/−), and wild-type mice on days 11, 12, and 13 after implantation of telemetry probe (n=5 to 7 per group). *P<0.05 compared with MC4R (−/−) mice. Reproduced from Tallam et al. 2005 with permission of the publisher. Copyright © 2005 American Heart Association. All rights reserved.
Figure 4
Figure 4
Blood Pressure in MC4-R deficiency. The graphs show measures of systolic blood pressure (Panel A) and diastolic blood pressure (Panel B) in 46 subjects with MC4R deficiency, as compared with 30 overweight or obese control subjects. Reproduced from Greenfield et al. 2009 with permission of the publisher. Copyright © 2009 Massachusetts Medical Society. All rights reserved.
Figure 5
Figure 5
Amount of volume of healthy myocardial tissue, as estimated 72 h after permanent coronary occlusion (CO) calculated as a percentage of the myocardial volume of the lateral wall of the left ventricle (LWLV), in sham-operated (n = 6), saline-treated (n = 8), and NDP-MSH-treated (0.27 mg/kg s.c. every 12 h; n = 8) rats (mean values ± S.E). *P < 0.001 versus saline-treated rats (Student-Newman-Keuls test). Reproduced from Bazzani et al. 2001 with permission of the publisher. Copyright © 2001 The American Society for Pharmacology and Experimental Therapeutics. All rights reserved.
Figure 6
Figure 6
The melanocortin system and inflammatory response. Physiological insult leads to a stress response comprising systemic inflammatory and local cytokine responses. Melanocortin peptides acting both directly upon inflammatory cells, and centrally via the MC3/4-R and vagal efferents, act to suppress these cytokine and systemic responses and therefore modulate the stress response. Abbreviations: TNFα, tumor necrosis factor α; MC3/4-R, melanocortin 3/4 receptor.
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