Abstract P178: The Role of Lateral Hypothalamic Leptin Signaling in Metabolic and Cardiovascular Regulation

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Huxing Cui ◽  
Eva Rodriguez Cruz
Keyword(s):  
Leptin Receptor ◽  
Nervous Activity ◽  
Cardiovascular Regulation ◽  
Brain Regions ◽  
Sympathetic Nervous Activity ◽  
Hypothalamic Area ◽  
Leptin Signaling ◽  
Lateral Hypothalamic ◽  
Sympathetic Regulation

While neurons in the lateral hypothalamic area (LHA) are clearly involved in feeding, metabolism, and cardiovascular regulation, neurochemically and neuroanatomically heterogeneous nature of LHA neurons has been a challenge in understanding their function in physiological regulation. We have recently identified a unique subset of LHA GABAergic neurons, which are distinct from well-known orexin and MCH neurons, that co-express two metabolically important leptin receptor (LepR) and melanocortin-4 receptor (MC4R), suggesting that these neurons might be the important targets of leptin and melanocortin for metabolic and cardiovascular regulation. Here we show that LHA LepR-positive neurons innervate broadly to intra- and extra-hypothalamic brain regions important for feeding, sympathetic nervous activity, and cardiovascular function, including but not limited to arcuate nucleus, paraventricular nucleus of hypothalamus, parabrachial nucleus, and nucleus of the solitary tract. Stereotaxic microinfusion of leptin into the LHA increases renal sympathetic nerve activity (RSNA) (% changes from baseline at 4 th hour: vehicle -25.03 ± 7.09 % vs leptin 100.23 ± 26.94 %, p<0.001); and specific deletion of LepR from LHA significantly increase body weight when fed high-fat diet (44.5 ± 1.9g vs 52.5 ± 2.5g, p<0.01); and selective chemogenetic activation of LHA LepR+ neurons decrease feeding and increase physical activity. Our findings identify the LHA as a novel brain site for leptin to integrate feeding, metabolism and sympathetic regulation. Further investigation of the role of LHA leptin signaling in blood pressure regulation is underway.

THE ROLE OF INCREASED SYMPATHETIC NERVOUS ACTIVITY FOR THE REDUCED RENAL BLOOD FLOW IN PATIENTS WITH CIRRHOSIS

1981 ◽  
Vol 1 (s1) ◽  
pp. 71-75 ◽  
Author(s):  
Helmer Ring-Larsen ◽  
Jens H. Henriksen ◽  
Birger Hesse ◽  
Niels Juel Christensen
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous

scholarly journals Temporal Leptin to Determine Cardiovascular and Metabolic Fate throughout the Life

Nutrients ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3256
Author(s):  
Jae Geun Kim ◽  
Byung Ju Lee ◽  
Jin Kwon Jeong
Keyword(s):  
Leptin Receptor ◽  
Metabolic Diseases ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Postnatal Life ◽  
Metabolic Fate ◽  
Body Adiposity ◽  
Current Review ◽  
The Central Nervous System

Leptin links peripheral adiposity and the central nervous system (CNS) to regulate cardiometabolic physiology. Within the CNS, leptin receptor-expressing cells are a counterpart to circulating leptin, and leptin receptor-mediated neural networks modulate the output of neuroendocrine and sympathetic nervous activity to balance cardiometabolic homeostasis. Therefore, disrupted CNS leptin signaling is directly implicated in the development of metabolic diseases, such as hypertension, obesity, and type 2 diabetes. Independently, maternal leptin also plays a central role in the development and growth of the infant during gestation. Accumulating evidence points to the dynamic maternal leptin environment as a predictor of cardiometabolic fate in their offspring as it is directly associated with infant metabolic parameters at birth. In postnatal life, the degree of serum leptin is representative of the level of body adiposity/weight, a driving factor for cardiometabolic alterations, and therefore, the levels of blood leptin through the CNS mechanism, in a large part, are a strong determinant for future cardiometabolic fate. The current review focuses on highlighting and discussing recent updates for temporal dissection of leptin-associated programing of future cardiometabolic fate throughout the entire life.

Thermogenesis after lateral hypothalamic lesions: contributions of brown adipose tissue

1988 ◽  
Vol 255 (5) ◽  
pp. E708-E715 ◽  
Author(s):  
S. W. Corbett ◽  
L. N. Kaufman ◽  
R. E. Keesey
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Nervous Activity ◽  
Male Rats ◽  
Sympathetic Nervous Activity ◽  
Primary Role ◽  
Interscapular Brown Adipose Tissue ◽  
Lateral Hypothalamic ◽  
Brown Adipose ◽  
The Hours

The role of brown adipose tissue in the thermogenic response to lateral hypothalamic (LH) lesions was investigated. Interscapular brown adipose tissue (IBAT) temperatures were measured during the hours following bilateral electrolytic LH lesions in male rats sedated with pentobarbital sodium. Local temperature changes were also recorded from skin and colonic sites. Consistent with the view that brown adipose tissue plays a primary role in the hyperthermia produced by LH lesions, IBAT depot temperature rose before, at a faster rate, and to a higher level than the other sites. In two subsequent experiments, oxygen consumption, activity, and core temperature were monitored in freely moving male rats with LH lesions, both in warm (25 degrees C) and cold (5 degrees C) environments. The results of these experiments provide some support for the view that LH lesions produce an increase in the regulated level of body temperature. This hyperthermic and hypermetabolic state seems to be mediated, in part, by brown fat thermogenesis and may represent a general increase in sympathetic nervous activity induced by the lesion.

scholarly journals Caloric restriction reverses the deficits in leptin receptor protein and leptin signaling capacity associated with diet-induced obesity: role of leptin in the regulation of hypothalamic long-form leptin receptor expression

2004 ◽  
Vol 181 (2) ◽  
pp. 297-306 ◽  
Author(s):  
J Wilsey ◽  
PJ Scarpace
Keyword(s):  
Caloric Restriction ◽  
Leptin Receptor ◽  
Fold Increase ◽  
Receptor Expression ◽  
Male Rats ◽  
Receptor Protein ◽  
Leptin Signaling ◽  
Stat3 Phosphorylation ◽  
Long Form

The objectives of this study were to determine if reduced long-form leptin receptor (ObRb) expression in diet-induced obese (DIO) animals is associated with deficits in maximal leptin signaling and, secondly, to establish the effects of short-term caloric restriction (CR) on ObRb expression and function. Groups of DIO and life-long chow-fed (CHOW) F344xBN male rats, aged 6 months, were given an i.c.v. injection containing 2 micro g leptin or artificial cerebrospinal fluid (ACSF) vehicle. Leptin induced a >6-fold increase in STAT3 phosphorylation in CHOW rats, but less than 2-fold increase in DIO. Reduced maximal leptin-stimulated STAT3 phosphorylation in DIO rats was coupled with a decline in both ObRb expression and protein. At this point, subgroups of DIO and CHOW animals underwent CR for 30 days and were then tested for acute leptin responsiveness. CR resulted in a 45 and 85% increase respectively in leptin-stimulated STAT3 phosphorylation in CHOW and DIO animals. Similarly, CR increased ObRb expression and protein in both CHOW and DIO animals. To explore the role of leptin in regulating ObRb expression, we reversibly overexpressed leptin in the hypothalamus and found that ObRb mRNA inversely follows central leptin expression. By enhancing both ObRb expression and signaling capacity, CR may enhance leptin responsiveness in leptin-resistant DIO animals.

scholarly journals The role of sympathetic nervous activity in renal injury and end-stage renal disease

2010 ◽  
Vol 33 (6) ◽  
pp. 521-528 ◽  
Author(s):  
Kazuko Masuo ◽  
Gavin W Lambert ◽  
Murray D Esler ◽  
Hiromi Rakugi ◽  
Toshio Ogihara ◽  
...  
Keyword(s):  
Renal Disease ◽  
Renal Injury ◽  
End Stage Renal Disease ◽  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous ◽  
Stage Renal Disease ◽  
End Stage

Mapping of microstimulation evoked responses and unit activity patterns in the lateral hypothalamic area recorded in awake humans

2011 ◽  
Vol 115 (2) ◽  
pp. 295-300 ◽  
Author(s):  
W. Bryan Wilent ◽  
Michael Y. Oh ◽  
Catherine Buetefisch ◽  
Julian E. Bailes ◽  
Diane Cantella ◽  
...  
Keyword(s):  
Lateral Hypothalamus ◽  
Activity Patterns ◽  
Brain Regions ◽  
Lateral Hypothalamic Area ◽  
Neurosurgical Procedures ◽  
Evoked Responses ◽  
Hypothalamic Area ◽  
Anatomical Distribution ◽  
Basal Nuclei ◽  
Lateral Hypothalamic

Major contributions to the understanding of human brain function have come from detailed clinical reports of responses evoked by electrical stimulation and specific brain regions during neurosurgical procedures in awake humans. In this study, microstimulation evoked responses and extracellular unit recordings were obtained intraoperatively in 3 awake patients undergoing bilateral implantation of deep brain stimulation electrodes in the lateral hypothalamus. The microstimulation evoked responses exhibited a clear anatomical distribution. Anxiety was most reliably evoked by stimulation directed ventromedially within or adjacent to the ventromedial nucleus of the hypothalamus, nausea was most reliably evoked by stimulation directed at the center of the lateral hypothalamus, and paresthesias were most reliably evoked by stimulation at the border of the lateral hypothalamus and basal nuclei. Regarding the unit recordings, the firing rates of individual neurons did not have an anatomical distribution, but a small subpopulation of neurons located at the border of the lateral hypothalamus and basal nuclei exhibited a fast rhythmically bursting behavior with an intraburst frequency of 200–400 Hz and an interburst frequency of 10–20 Hz. Based on animal studies, the lateral hypothalamic area and surrounding hypothalamic nuclei are putatively involved with a variety of physiological, behavioral, and sensory functions. The lateral hypothalamus is situated to play a dynamic and complex role in human behavior and this report further shows that to be true. In addition, this report should serve as a valuable resource for future intracranial work in which accurate targeting within this region is required.

Role of alpha1 and alpha2-adrenoceptors of the lateral hypothalamic area on urinary excretion caused by centrally administered angiotensin II

1995 ◽  
Vol 194 (3) ◽  
pp. 169-172
Author(s):  
Wilson Abrão Saad ◽  
Luiz Antonio de Arruda Camargo ◽  
Antonio Renzi ◽  
JoséVanderlei Menani ◽  
Willian Abrão Saad
Keyword(s):  
Angiotensin Ii ◽  
Urinary Excretion ◽  
Lateral Hypothalamic Area ◽  
Hypothalamic Area ◽  
Lateral Hypothalamic

Role of the Autonomic Nervous System in Mild Human Hypertension

1974 ◽  
Vol 48 (s2) ◽  
pp. 243s-252s ◽  
Author(s):  
S. Julius ◽  
M. D. Esler ◽  
O. S. Randall
Keyword(s):  
Vascular Resistance ◽  
Mild Hypertension ◽  
Nervous Activity ◽  
Plasma Renin ◽  
Sympathetic Nervous Activity ◽  
Peripheral Vascular ◽  
Autonomic Tone ◽  
Human Hypertension ◽  
Autonomic Blockade

1. Some of the haemodynamic abnormalities in mild (borderline) human hypertension appear to be neurogenic, since they can be completely abolished by pharmacological autonomic blockade. 2. The cardiac output is elevated in 30% of patients through increased sympathetic drive and decreased parasympathetic inhibition. 3. In the remainder, the higher blood pressure is maintained by increased total peripheral vascular resistance. 4. In approximately 30% of this latter group, the higher vascular resistance is maintained solely by increased alpha-adrenergic tone. 5. Elevated plasma renin activities in a proportion of cases are probably due to generalized increase in sympathetic nervous activity. 6. Patients with mild hypertension thus show increased sympathetic drive to the heart and arterioles as well as decreased cardiac parasympathetic inhibition. It is presumed that the increased plasma renin is also neurogenic. 7. Such a widespread distribution of altered autonomic tone suggests aberration of the function of the integrative centres of cardiovascular control. 8. Evidence is presented of a possible psychosomatic origin of these changes in some cases.

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