Cardiovascular Regulation by the Arcuate Nucleus of the Hypothalamus

Rahmouni, Kamal

doi:10.1161/hypertensionaha.115.06425

Cited by 49 publications

(41 citation statements)

References 79 publications

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“…Thus, POMC and AgRP neurons are considered as critical antagonistic components of the melanocortin system. Leptin activates anorexigenic POMC neurons while simultaneously inhibit orexigenic AgRP neurons [38, 39]. …”

Section: Neuronal Substrates Of Leptin Actionmentioning

confidence: 99%

Leptin as a Mediator of Obesity-Induced Hypertension

2016

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Hypertension and associated cardiovascular diseases represent the most common health complication of obesity and the leading cause of morbidity and mortality in overweight and obese patients. Emerging evidence suggests a critical role for the central nervous system particularly the brain action of the adipocyte-derived hormone leptin in linking obesity and hypertension. The preserved ability of leptin to cause cardiovascular sympathetic nerve activation despite the resistance to the metabolic actions of the hormone appears essential in this pathological process. This review describes the evidence supporting the neurogenic bases for obesity-associated hypertension with a particular focus on the neuronal and molecular signaling pathways underlying leptin’s effects on sympathetic nerve activity and blood pressure.

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Section: Neuronal Substrates Of Leptin Actionmentioning

confidence: 99%

Leptin as a Mediator of Obesity-Induced Hypertension

2016

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“…The ARC is located within the mediobasal hypothalamus and is the critical brain region regulating energy homeostasis (McNay et al, 2012). It is optimally positioned for its function and is often described as a "window" to sense nutrients and hormonal signals in circulation and therefore able to mediate appropriate metabolic responses (Langlet, 2014;Rahmouni, 2016). The ARC contains both anorexigenic and orexigenic neurons which perform opposing functions in order to control appetite and regulate energy metabolism (Benite-Ribeiro, Putt, Soares-Filho, & Santos, 2016).…”

Section: The Arcuate N Ucleus and Energy Homeos Ta S Ismentioning

confidence: 99%

Diet‐induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity

Samodien

Erasmus

Mabasa

et al. 2019

Food Science & Nutrition

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Obesity rates continue to rise in an unprecedented manner in what could be the most rapid population‐scale shift in human phenotype ever to occur. Increased consumption of unhealthy, calorie‐dense foods, coupled with sedentary lifestyles, is the main factor contributing to a positive energy balance and the development of obesity. Leptin and insulin are key hormones implicated in pathogenesis of this disorder and are crucial for controlling whole‐body energy homeostasis. Their respective function is mediated by the counterbalance of anorexigenic and orexigenic neurons located within the hypothalamic arcuate nucleus. Dysregulation of leptin and insulin signaling pathways within this brain region may contribute not only to the development of obesity, but also systemically affect the peripheral organs, thereby manifesting as metabolic diseases. Although the exact mechanisms detailing how these hypothalamic nuclei contribute to disease pathology are still unclear, increasing evidence suggests that altered DNA methylation may be involved. This review evaluates animal studies that have demonstrated diet‐induced DNA methylation changes in genes that regulate energy homeostasis within the arcuate nucleus, and elucidates possible mechanisms causing hypothalamic leptin and insulin resistance leading to the development of obesity and metabolic diseases.

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“…The involvement of POMC and AgRP neurons in the control of autonomic nerve activity subserving various beds is consistent with the pleiotropic actions of these neurons. The divergent signaling capacities of POMC and AgRP neurons afforded by the presence of multiple neurotransmitters [51] may underlie the regional SNA and PSNA responses evoked by leptin action in these neurons. In support of such possibility leptin control of lumbar SNA involve both MC3/4R and glutamate receptors in the second order neurons [128] whereas the renal sympathoexcitatory effect of leptin is mediated by the MC4R [129].…”

Section: Discussionmentioning

confidence: 99%

“…The arcuate nucleus of the hypothalamus (ARC) is critically involved in the regulation of several physiological processes including metabolic and cardiovascular functions [51,92]. The leptin receptor (LepR) is highly expressed in the ARC and accumulating evidence points to the importance of the ARC for leptin control of both SNA and PSNA.…”

Section: Methodsmentioning

confidence: 99%

“…For instance, the majority of POMC neurons express cocaine-and amphetamine-regulating transcript whereas a subset of these neurons produces γ-aminobutyric acid (GABA), glutamate or acetylcholine. On the other hand, most AgRP neurons release neuropeptide Y and/or GABA [51]. However, the relative importance of POMC and AgRP neurons in mediating the regional sympathetic and parasympathetic effects of leptin remain unknown.…”

Section: Methodsmentioning

confidence: 99%

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Hypothalamic mechanisms underlying the cardiovascular and metabolic actions of leptin

Bell¹

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____________________________________________ Yuriy Usachev ____________________________________________ Huxing Cuiii To the people who believed in me, even when I didn't.iii *oh, be joyful* iv ACKNOWLEDGEMENTS It is so important to me to thank the many individuals without whom this work would not have been possible. I've always believed that science is most successful as a collaborative endeaver, and that together we are greater than the sum of our individual contributions. I wouldn't be the scientist or the person I am today without the support of people who cared about and believed in me. To my mentor, Kamal Rahmouni, for his guidance, patience, and understanding. To the entire Rahmouni lab, especially Don Morgan for his unparalleled technical expertise. To Deng Guo and Ken Muta for always looking out for me, and to Mohamed Rouabhi for letting me look out for you. To Dr. Allyn Mark, who will always be an inspiration and to my thesis committee for investing their time and talents in me. To the mice, for their valiant efforts in the name of science and in spite thereof. To my family, who taught me to be curious, to question dogma, to advocate for what's right, and to leave the world a better place that I found it. And to my James, who lifts me up in every way. I can never thank you enough. v ABSTRACT Secreted by adipose tissue, leptin acts as a signal of energy reserve status, and acts in the brain as a negative feedback mechanism to suppress food intake and increase energy expenditure, the net effect of which is maintenance of energy homeostasis. In addition to its role as a satiety factor, leptin has widespread autonomic effects, increasing sympathetic tone to a variety of tissues, including those involved in arterial pressure regulation. Thus, leptin has been implicated as a critical link between obesity and hypertension. However, the specific mechanisms whereby leptin elicits its diverse effects are not fully understood. This is further complicated by the many sites of leptin action within the brain, as well as its diverse intracellular effects. Here, we investigate the possibility that distinct aspects of leptin function are controlled by different neuronal populations and/or molecular signaling cascades. Specifically, we identify unique roles for leptin action on POMC and AgRP neurons in differentially mediating the regional sympathetic effects of leptin. Furthermore, we show that leptin action via mTORC1 is required for the cardiovascular sympathetic but not the metabolic effects. Together, these findings point to complex neuroanatomical and molecular differences in the mechanisms underlying leptin's effects on different physiological processes, with important implications for future research into obesity-associated hypertension. vi PUBLIC ABSTRACTObesity is a global health crisis. As the second-leading cause of preventable death in the United States, obesity is a major public health concern primarily because it is a risk factor for numerous co-morbid conditions including cardiovascular disease. The mechan...

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Cardiovascular Regulation by the Arcuate Nucleus of the Hypothalamus

Cited by 49 publications

References 79 publications

Leptin as a Mediator of Obesity-Induced Hypertension

Leptin as a Mediator of Obesity-Induced Hypertension

Diet‐induced DNA methylation within the hypothalamic arcuate nucleus and dysregulated leptin and insulin signaling in the pathophysiology of obesity

Hypothalamic mechanisms underlying the cardiovascular and metabolic actions of leptin

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