The brain melanocortin system, sympathetic control, and obesity hypertension.

@article{daSilva2014TheBM,
  title={The brain melanocortin system, sympathetic control, and obesity hypertension.},
  author={Alexandre A. da Silva and Jussara M. do Carmo and Zhen Wang and John E. Hall},
  journal={Physiology},
  year={2014},
  volume={29 3},
  pages={
          196-202
        }
}
Excess weight gain is the most significant, preventable cause of increased blood pressure (BP) in patients with primary (essential) hypertension and increases the risk for cardiovascular and renal diseases. In this review, we discuss the role of the brain melanocortin system in causing increased sympathetic activity in obesity and other forms of hypertension. In addition, we highlight potential mechanisms by which the brain melanocortin system modulates metabolic and cardiovascular functions. 

Figures from this paper

Obesity-Induced Hypertension: Brain Signaling Pathways
TLDR
Unraveling the CNS mechanisms responsible for increased sympathetic activation and hypertension and how circulating hormones activate brain signaling pathways to control BP offer potentially important therapeutic targets for obesity and hypertension.
Melanocortin-4 Receptors and Sympathetic Nervous System Activation in Hypertension
TLDR
MC4R is a potential target for antiobesity therapy, although there are challenges in using MC4R agonists to induce weight loss without evoking increases in SNS activity.
Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms.
TLDR
With prolonged obesity and development of target organ injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation.
Leptin, the Autonomic Nervous System, and Hypertension
TLDR
The crosstalk between peripheral signals and activation of CNS pathways (e.g. leptin) in key hypothalamic and brainstem areas that regulate energy balance, SNS activity, and BP represents a potential target for treating obesity and its metabolic and cardiovascular consequences.
Role of the Melanocortin System in the Central Regulation of Cardiovascular Functions
TLDR
The current knowledge of how the melanocortin system influences essential cardiovascular functions, such as blood pressure and heart rate, and its protective role in ischemic events is discussed, with a particular focus on the central regulation of such mechanisms.
Interaction of Neurohumoral and Renal Mechanisms
TLDR
With prolonged obesity and development of target organ injury, especially renal injury, obesity-associated hypertension becomes more difficult to control, often requiring multiple antihypertensive drugs and treatment of other risk factors, including dyslipidemia, insulin resistance and diabetes mellitus, and inflammation.
Should the sympathetic nervous system be a target to improve cardiometabolic risk in obesity?
TLDR
Preliminary evidence is encouraging, but more trials are needed to investigate whether sympathetic inhibition could be used in obesity to reverse or prevent cardiometabolic disease development and the potential benefits of sympathoinhibition on metabolic and cardiovascular functions.
Central role for melanocortin-4 receptors in offspring hypertension arising from maternal obesity
TLDR
It is shown that maternal obesity permanently resets the responsiveness of the central sympathetic nervous system via this pathway, and neonatal leptin exposure is the primary mediator, thereby contributing to offspring hypertension.
Obesity, kidney dysfunction and hypertension: mechanistic links
TLDR
The authors discuss the complex interactions between renal, hormonal and nervous system factors that link excess adiposity with elevated blood pressure and chronic obesity-associated hypertension.
Origin of Aberrant Blood Pressure and Sympathetic Regulation in Diet-Induced Obesity
TLDR
The VMH is the likely origin of leptin-mediated sympathoexcitation and &agr;-MSH hypersensitivity that contribute to obesity-related hypertension.
...
...

References

SHOWING 1-10 OF 64 REFERENCES
Obesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins*
TLDR
Several mechanisms contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system, which appears to be mediated in part by increased levels of the adipocyte-derived hormone leptin, stimulation of pro-opiomelanocortin neurons, and subsequent activation of central nervous system melanOCortin 4 receptors.
The role of the sympathetic nervous system in obesity-related hypertension
TLDR
Several potential mechanisms have been suggested to contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system and the renin-angiotensin-aldosterone system, as well as physical compression of the kidneys.
Modulation of blood pressure by central melanocortinergic pathways.
  • T. Maier, J. Hoyer
  • Biology, Medicine
    Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
  • 2010
TLDR
The authors assessed blood pressure, heart rate, and urinary catecholamines in overweight or obese subjects with a loss-of-function mutation in MC4R, the gene encoding the melanocortin 4 receptor, and in equally overweight control subjects.
Modulation of blood pressure by central melanocortinergic pathways.
TLDR
Results of the genetic and pharmacologic studies implicate melanocortinergic signaling in the control of human blood pressure through an insulin-independent mechanism.
Science of self-preservation: how melanocortin action in the brain modulates body weight, blood pressure, and ischemic damage.
Obesity is a major medical problem with a prevalence that is increasing at an alarming rate.1 It remains a major risk factor for cardiovascular disease, metabolic diseases like type 2 diabetes
Activation of the central melanocortin system contributes to the increased arterial pressure in obese Zucker rats.
TLDR
Results suggest that in obese Zucker rats the CNS melanocortin system contributes to elevated BP independent of leptin receptor activation, as well as plasma leptin and insulin levels markedly increased in lean Zucker rats during CNS MC3/4R antagonism.
Obesity and hypertension: two epidemics or one?
  • K. Davy, J. Hall
  • Medicine, Biology
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 2004
TLDR
The present review will provide an overview of the understanding of the etiology, pathophysiology, and treatment of obesity hypertension in humans, with a focus on the state of knowledge in humans.
Endogenous Melanocortin System Activity Contributes to the Elevated Arterial Pressure in Spontaneously Hypertensive Rats
TLDR
The results suggest that endogenous activity of the CNS melanocortin system contributes to the maintenance of adrenergic tone and elevated arterial pressure in SHR even though mRNA levels for POMC and MC4R in the mediobasal hypothalamus were not increased compared to WKY.
Selective leptin resistance revisited.
  • A. Mark
  • Biology
    American journal of physiology. Regulatory, integrative and comparative physiology
  • 2013
TLDR
A critical analysis of the concept of selective leptin resistance (SLR), the role of leptin in the pathogenesis of obesity-induced hypertension in both experimental animals and humans, and perplexing data on the effects of leptin on sympathetic activity and BP in humans are reviewed.
The kidney, hypertension, and obesity.
  • J. Hall
  • Medicine, Biology
    Hypertension
  • 2003
TLDR
There are many unanswered questions about the mechanisms of obesity hypertension and renal disease, but this is one of the most promising areas for future research, especially in view of the growing, worldwide "epidemic" of obesity.
...
...