Skip to main content
Hauptrubriken
CME Facharzt-Training Webinare Zeitschriften Bücher e.Medpedia Podcast
Service
Jobbörse Info & Hilfe
Fachgebiete
Anästhesiologie Allgemeinmedizin Arbeitsmedizin Augenheilkunde Chirurgie Dermatologie Gynäkologie und Geburtshilfe HNO Innere Medizin Kardiologie Neurologie Onkologie und Hämatologie Orthopädie und Unfallchirurgie Pädiatrie Pathologie Psychiatrie Radiologie Rechtsmedizin Urologie Zahnmedizin
Themen
Klimawandel und Gesundheit Neues aus dem Markt COVID-19 Praxis und Beruf Seltene Erkrankungen GOÄ & EBM Panorama
Sammlungen
Kasuistiken Algorithmen & Infografiken Blickdiagnosen Arthropedia FlapFinder (für Dermatochirurgen) Videos Kongressberichterstattung Medizin für Apothekerinnen und Apotheker Für Ärztinnen und Ärzte in Weiterbildung Für Medizinstudierende
Erweiterte Suche
Anmelden
nach oben
Current Obesity Reports
Erschienen in: Current Obesity Reports 4/2016

24.09.2016 | Metabolism (J Proietto, Section Editor)

Leptin as a Mediator of Obesity-Induced Hypertension

verfasst von: Balyssa B. Bell, Kamal Rahmouni

Erschienen in: Current Obesity Reports | Ausgabe 4/2016

Einloggen, um Zugang zu erhalten

Abstract

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.
Literatur
1.
Garrison RJ et al. Incidence and precursors of hypertension in young adults: the Framingham Offspring Study. Prev Med. 1987;16(2):235–51.CrossRefPubMed
2.
Holecki M, Dulawa J, Chudek J. Resistant hypertension in visceral obesity. Eur J Intern Med. 2012;23(7):643–8.CrossRefPubMed
3.
Fidan-Yaylali G et al. The association between central adiposity and autonomic dysfunction in obesity. Med Princ Pract. 2016;25:442.CrossRefPubMed
4.
5.
Esler M et al. Mechanisms of sympathetic activation in obesity-related hypertension. Hypertension. 2006;48(5):787–96.CrossRefPubMed
6.
Neter JE et al. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2003;42(5):878–84.CrossRefPubMed
7.
Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009;53(21):1925–32.CrossRefPubMed
8.
Straznicky NE et al. Effects of dietary weight loss on sympathetic activity and cardiac risk factors associated with the metabolic syndrome. J Clin Endocrinol Metab. 2005;90(11):5998–6005.CrossRefPubMed
9.
Fortmann SP, Haskell WL, Wood PD. Effects of weight loss on clinic and ambulatory blood pressure in normotensive men. Am J Cardiol. 1988;62(1):89–93.CrossRefPubMed
10.
Williams IL et al. Endothelial function and weight loss in obese humans. Obes Surg. 2005;15(7):1055–60.CrossRefPubMed
11.••
Skinner AC et al. Cardiometabolic risks and severity of obesity in children and young adults. N Engl J Med. 2015;373(14):1307–17. The work reported in this paper demonstrate the close link between obesity, hypertension and other cardiovascular risks in children.CrossRefPubMed
12.
Twig G et al. Body-mass index in 2.3 million adolescents and cardiovascular death in adulthood. N Engl J Med. 2016;374(25):2430–40.CrossRefPubMed
13.
Hubert HB et al. Obesity as an independent risk factor for cardiovascular disease: a 26-year follow-up of participants in the Framingham Heart Study. Circulation. 1983;67(5):968–77.CrossRefPubMed
14.
Kurajoh M et al. Plasma leptin level is associated with cardiac autonomic dysfunction in patients with type 2 diabetes: HSCAA study. Cardiovasc Diabetol. 2015;14:117.CrossRefPubMedPubMedCentral
15.
Selvaraj S et al. Association of central adiposity with adverse cardiac mechanics: findings from the hypertension genetic epidemiology network study. Circ Cardiovasc Imaging. 2016;9(6):e004396.CrossRefPubMed
16.
17.
Alvarez GE et al. Sympathetic neural activation in visceral obesity. Circulation. 2002;106(20):2533–6.CrossRefPubMed
18.
Lambert E et al. Differing pattern of sympathoexcitation in normal-weight and obesity-related hypertension. Hypertension. 2007;50(5):862–8.CrossRefPubMed
19.
Grassi G et al. Sympathetic activation in obese normotensive subjects. Hypertension. 1995;25(4 Pt 1):560–3.CrossRefPubMed
20.
Cooper JN et al. Associations between arterial stiffness and platelet activation in normotensive overweight and obese young adults. Clin Exp Hypertens. 2014;36(3):115–22.CrossRefPubMed
21.
Robinson MR et al. Uncomplicated obesity is associated with abnormal aortic function assessed by cardiovascular magnetic resonance. J Cardiovasc Magn Reson. 2008;10:10.CrossRefPubMedPubMedCentral
22.
Masuo K et al. Differences in mechanisms between weight loss-sensitive and -resistant blood pressure reduction in obese subjects. Hypertens Res. 2001;24(4):371–6.CrossRefPubMed
23.
Muntzel MS et al. Cafeteria diet increases fat mass and chronically elevates lumbar sympathetic nerve activity in rats. Hypertension. 2012;60(6):1498–502.CrossRefPubMedPubMedCentral
24.
Armitage JA et al. Rapid onset of renal sympathetic nerve activation in rabbits fed a high-fat diet. Hypertension. 2012;60(1):163–71.CrossRefPubMed
25.
Henegar JR et al. Catheter-based radiorefrequency renal denervation lowers blood pressure in obese hypertensive dogs. Am J Hypertens. 2014;27(10):1285–92.CrossRefPubMedPubMedCentral
26.•
Bhatt DL et al. A controlled trial of renal denervation for resistant hypertension. N Engl J Med. 2014;370(15):1393–401. This study reported the finding from SIMPLICITY-3 trials showing that in patients with resistant hypertension, the effect of renal denervation is similar to sham intervention.CrossRefPubMed
27.
Shibao C et al. Autonomic contribution to blood pressure and metabolism in obesity. Hypertension. 2007;49(1):27–33.CrossRefPubMed
28.•
Simonds SE et al. Leptin mediates the increase in blood pressure associated with obesity. Cell. 2014;159(6):1404–16. This paper confirmed the critical role for leptin in mediating obesity-associated hypertension both in humans and animal models.CrossRefPubMedPubMedCentral
29.
30.
31.
Lim K, Burke SL, Head GA. Obesity-related hypertension and the role of insulin and leptin in high-fat-fed rabbits. Hypertension. 2013;61(3):628–34.CrossRefPubMed
32.
Mark AL et al. Contrasting blood pressure effects of obesity in leptin-deficient ob/ob mice and agouti yellow obese mice. J Hypertens. 1999;17(12 Pt 2):1949–53.CrossRefPubMed
33.
Ozata M, Ozdemir IC, Licinio J. Human leptin deficiency caused by a missense mutation: multiple endocrine defects, decreased sympathetic tone, and immune system dysfunction indicate new targets for leptin action, greater central than peripheral resistance to the effects of leptin, and spontaneous correction of leptin-mediated defects. J Clin Endocrinol Metab. 1999;84(10):3686–95.CrossRefPubMed
34.
Minocci A et al. Leptin plasma concentrations are dependent on body fat distribution in obese patients. Int J Obes Relat Metab Disord. 2000;24(9):1139–44.CrossRefPubMed
35.
Van Harmelen V et al. Leptin secretion from subcutaneous and visceral adipose tissue in women. Diabetes. 1998;47(6):913–7.CrossRefPubMed
36.
Cnop M et al. The concurrent accumulation of intra-abdominal and subcutaneous fat explains the association between insulin resistance and plasma leptin concentrations: distinct metabolic effects of two fat compartments. Diabetes. 2002;51(4):1005–15.CrossRefPubMed
37.
38.
van de Wall E et al. Collective and individual functions of leptin receptor modulated neurons controlling metabolism and ingestion. Endocrinology. 2008;149(4):1773–85.CrossRefPubMed
39.
Rahmouni K. Cardiovascular regulation by the arcuate nucleus of the hypothalamus: neurocircuitry and signaling systems. Hypertension. 2016;67(6):1064–71.CrossRefPubMed
40.
Harlan SM et al. Ablation of the leptin receptor in the hypothalamic arcuate nucleus abrogates leptin-induced sympathetic activation. Circ Res. 2011;108(7):808–12.CrossRefPubMedPubMedCentral
41.
Rahmouni K, Morgan DA. Hypothalamic arcuate nucleus mediates the sympathetic and arterial pressure responses to leptin. Hypertension. 2007;49(3):647–52.CrossRefPubMed
42.
do Carmo JM et al. Control of blood pressure, appetite, and glucose by leptin in mice lacking leptin receptors in proopiomelanocortin neurons. Hypertension. 2011;57(5):918–26.CrossRefPubMedPubMedCentral
43.•
Lim K et al. Origin of aberrant blood pressure and sympathetic regulation in diet-induced obesity. Hypertension. 2016;68(2):491–500. This paper investigates the role of various hypothalamic regions in mediating leptin’s contribution to obesity-associated hypertension.CrossRefPubMed
44.
Marsh AJ et al. Cardiovascular responses evoked by leptin acting on neurons in the ventromedial and dorsomedial hypothalamus. Hypertension. 2003;42(4):488–93.CrossRefPubMed
45.
Shih CD, Au LC, Chan JY. Differential role of leptin receptors at the hypothalamic paraventricular nucleus in tonic regulation of food intake and cardiovascular functions. J Biomed Sci. 2003;10(4):367–78.CrossRefPubMed
46.
Mark AL et al. Leptin signaling in the nucleus tractus solitarii increases sympathetic nerve activity to the kidney. Hypertension. 2009;53(2):375–80.CrossRefPubMed
47.
Smith PM, Ferguson AV. Cardiovascular actions of leptin in the subfornical organ are abolished by diet-induced obesity. J Neuroendocrinol. 2012;24(3):504–10.CrossRefPubMed
48.
Young CN et al. The brain subfornical organ mediates leptin-induced increases in renal sympathetic activity but not its metabolic effects. Hypertension. 2013;61(3):737–44.CrossRefPubMed
49.
Farooqi IS et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085–95.CrossRefPubMed
50.
Greenfield JR et al. Modulation of blood pressure by central melanocortinergic pathways. N Engl J Med. 2009;360(1):44–52.CrossRefPubMed
51.
Tallam LS et al. Melanocortin-4 receptor-deficient mice are not hypertensive or salt-sensitive despite obesity, hyperinsulinemia, and hyperleptinemia. Hypertension. 2005;46(2):326–32.CrossRefPubMed
52.
Rahmouni K et al. Role of melanocortin-4 receptors in mediating renal sympathoactivation to leptin and insulin. J Neurosci. 2003;23(14):5998–6004.PubMed
53.
Bates SH et al. STAT3 signalling is required for leptin regulation of energy balance but not reproduction. Nature. 2003;421(6925):856–9.CrossRefPubMed
54.
Gao Q et al. Disruption of neural signal transducer and activator of transcription 3 causes obesity, diabetes, infertility, and thermal dysregulation. Proc Natl Acad Sci U S A. 2004;101(13):4661–6.CrossRefPubMedPubMedCentral
55.
56.•
Dubinion JH et al. Role of proopiomelanocortin neuron STAT3 in regulating arterial pressure and mediating the chronic effects of leptin. Hypertension. 2013;61(5):1066–74. This paper demonstrates a critical role for STAT3 signaling in POMC neurons in mediating both the metabolic and cardiovascular sympathetic effects of leptin.CrossRefPubMedPubMedCentral
57.
Munzberg H, Flier JS, Bjorbaek C. Region-specific leptin resistance within the hypothalamus of diet-induced obese mice. Endocrinology. 2004;145(11):4880–9.CrossRefPubMed
58.
Patterson CM et al. Leptin action via LepR-b Tyr1077 contributes to the control of energy balance and female reproduction. Mol Metab. 2012;1(1–2):61–9.CrossRefPubMedPubMedCentral
59.
Cota D et al. Hypothalamic mTOR signaling regulates food intake. Science. 2006;312(5775):927–30.CrossRefPubMed
60.
61.••
Harlan SM et al. Hypothalamic mTORC1 signaling controls sympathetic nerve activity and arterial pressure and mediates leptin effects. Cell Metab. 2013;17(4):599–606. This is the first report to implicate hypothalamic mTORC1 in sympathetic and cardiovascular regulation.CrossRefPubMedPubMedCentral
62.
Harlan SM, Rahmouni K. PI3K signaling: a key pathway in the control of sympathetic traffic and arterial pressure by leptin. Mol Metab. 2013;2(2):69–73.CrossRefPubMedPubMedCentral
63.
64.
Do Carmo JM et al. Shp2 signaling in POMC neurons is important for leptin’s actions on blood pressure, energy balance, and glucose regulation. Am J Physiol Regul Integr Comp Physiol. 2014;307(12):R1438–47.CrossRefPubMedPubMedCentral
65.
do Carmo JM et al. Role of Shp2 in forebrain neurons in regulating metabolic and cardiovascular functions and responses to leptin. Int J Obes (Lond). 2014;38(6):775–83.CrossRef
66.
Bjorbaek C et al. Identification of SOCS-3 as a potential mediator of central leptin resistance. Mol Cell. 1998;1(4):619–25.CrossRefPubMed
67.
Pedroso JA et al. Inactivation of SOCS3 in leptin receptor-expressing cells protects mice from diet-induced insulin resistance but does not prevent obesity. Mol Metab. 2014;3(6):608–18.CrossRefPubMedPubMedCentral
68.
Bence KK et al. Neuronal PTP1B regulates body weight, adiposity and leptin action. Nat Med. 2006;12(8):917–24.CrossRefPubMed
69.
Belin de Chantemele EJ et al. Protein tyrosine phosphatase 1B, a major regulator of leptin-mediated control of cardiovascular function. Circulation. 2009;120(9):753–63.CrossRefPubMed
70.
Bruder-Nascimento T et al. Deletion of protein tyrosine phosphatase 1b in proopiomelanocortin neurons reduces neurogenic control of blood pressure and protects mice from leptin- and sympatho-mediated hypertension. Pharmacol Res. 2015;102:235–44.CrossRefPubMed
Metadaten
Titel
Leptin as a Mediator of Obesity-Induced Hypertension
verfasst von
Balyssa B. Bell
Kamal Rahmouni
Publikationsdatum
24.09.2016
Verlag
Springer US
Erschienen in
Current Obesity Reports / Ausgabe 4/2016
Elektronische ISSN: 2162-4968
DOI
https://doi.org/10.1007/s13679-016-0231-x

Weitere Artikel der Ausgabe 4/2016

Current Obesity Reports 4/2016 Zur Ausgabe

Metabolism (J Proietto, Section Editor)

Psychological Impact of Severe Obesity

Economy and Environment (GJ Egger, Section Editor)

Global Changes in Food Supply and the Obesity Epidemic

Metabolism (J Proietto, Section Editor)

Effects of Obesity on Cardiovascular Hemodynamics, Cardiac Morphology, and Ventricular Function

Economy and Environment (GJ Egger, Section Editor)

Economic Growth, Climate Change, and Obesity

Invited Commentary

Maintaining Weight Loss: an Ongoing Challenge

Invited Commentary

The Mass of Humanity and the Weight of the World: Obesity and the Environment at a Confluence of Causes

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Echinokokkose medikamentös behandeln oder operieren?

06.05.2024 DCK 2024 Kongressbericht

Die Therapie von Echinokokkosen sollte immer in spezialisierten Zentren erfolgen. Eine symptomlose Echinokokkose kann – egal ob von Hunde- oder Fuchsbandwurm ausgelöst – konservativ erfolgen. Wenn eine Op. nötig ist, kann es sinnvoll sein, vorher Zysten zu leeren und zu desinfizieren. 

Umsetzung der POMGAT-Leitlinie läuft

03.05.2024 DCK 2024 Kongressbericht

Seit November 2023 gibt es evidenzbasierte Empfehlungen zum perioperativen Management bei gastrointestinalen Tumoren (POMGAT) auf S3-Niveau. Vieles wird schon entsprechend der Empfehlungen durchgeführt. Wo es im Alltag noch hapert, zeigt eine Umfrage in einem Klinikverbund.

Proximale Humerusfraktur: Auch 100-Jährige operieren?

01.05.2024 DCK 2024 Kongressbericht

Mit dem demographischen Wandel versorgt auch die Chirurgie immer mehr betagte Menschen. Von Entwicklungen wie Fast-Track können auch ältere Menschen profitieren und bei proximaler Humerusfraktur können selbst manche 100-Jährige noch sicher operiert werden.

Die „Zehn Gebote“ des Endokarditis-Managements

30.04.2024 Endokarditis Leitlinie kompakt

Worauf kommt es beim Management von Personen mit infektiöser Endokarditis an? Eine Kardiologin und ein Kardiologe fassen die zehn wichtigsten Punkte der neuen ESC-Leitlinie zusammen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen
Bildnachweise