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.

scholarly journals Relationships of Adrenoceptor Polymorphisms with Obesity

2011 ◽  
Vol 2011 ◽  
pp. 1-10 ◽  
Author(s):  
Kazuko Masuo ◽  
Gavin W. Lambert
Keyword(s):  
Type 2 Diabetes ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Vascular Reactivity ◽  
Nervous Activity ◽  
Epidemiological Studies ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous ◽  
Obesity Hypertension

Obesity, hypertension, and type 2 diabetes are rapidly growing public health problems. Heightened sympathetic nerve activity is a well-established observation in obesity, hypertension, and type 2 diabetes. Human obesity, hypertension, and diabetes have strong genetic as well as environmental determinants. Reduced energy expenditure and resting metabolic rate are predictive of weight gain, and the sympathetic nervous system participates in regulating energy balance through thermogenesis. The thermogenic effects of catecholamines in obesity are mainly mediated via the β2, and β3-adrenergic receptors in humans. Further, β2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. β-adrenoceptor polymorphisms have also been associated with adrenoceptor desensitization, increased adiposity, insulin resistance, and enhanced sympathetic nervous activity. Many epidemiological studies have shown strong relationships between adrenoceptor polymorphisms and obesity, but the observations have been discordant. This paper will discuss the current topics involving the influence of the sympathetic nervous system and β2- and β3-adrenoceptor polymorphisms in obesity.

scholarly journals Recessive genetic effects on type 2 diabetes-related metabolites in a consanguineous population

2019 ◽  
Author(s):  
Ayşe Demirkan ◽  
Jun Liu ◽  
Najaf Amin ◽  
Jan B van Klinken ◽  
Ko Willems van Dijk ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Autosomal Recessive ◽  
Metabolic Diseases ◽  
Genetic Model ◽  
Autosomal Recessive Inheritance ◽  
P Value ◽  
Recessive Mutations ◽  
Nominal Significance ◽  
The Central Nervous System

AbstractAutozygosity, meaning inheritance of an ancestral allele in the homozygous state is known to lead bi-allelic mutations that manifest their effects through the autosomal recessive inheritance pattern. Autosomal recessive mutations are known to be the underlying cause of several Mendelian metabolic diseases, especially among the offspring of related individuals. In line with this, inbreeding coefficient of an individual as a measure of cryptic autozygosity among the general population is known to lead adverse metabolic outcomes including Type 2 diabetes (T2DM); a multifactorial metabolic disease for which the recessive genetic causes remain unknown. In order to unravel such effects for multiple metabolic facades of the disease, we investigated the relationship between the excess of homozygosity and the metabolic signature of T2DM. We included a set of 53 metabolic phenotypes, including 47 metabolites, T2DM and five T2DM risk factors, measured in a Dutch genetic isolate of 2,580 people. For 20 of these markers, we identified 29 regions of homozygous (ROHs) associated with the nominal significance of P-value < 1.0 × 10−3. By performing association according to the recessive genetic model within these selected regions, we identified and replicated two intronic variants: rs6759814 located in KCNH7 associated with valine and rs1573707 located in PTPRT associated with IDL-free cholesterol and IDL-phospholipids. Additionally, we identified a rare intronic SNV in TBR1 for which the homozygous individuals were enriched for obesity. Interestingly, all three genes are mainly neuronally expressed and pointed out the involvement of glutamergic synaptic transmission pathways in the regulation of metabolic pathways. Taken together our study underline the additional benefits of model supervised analysis, but also seconds the involvement of the central nervous system in T2DM and obesity pathogenesis.

β-Receptor-Blockade Hypotension and the Central Nervous System

1976 ◽  
Vol 51 (s3) ◽  
pp. 549s-550s
Author(s):  
P. J. Lewis
Keyword(s):  
Blood Pressure ◽  
Nervous Activity ◽  
Splanchnic Nerve ◽  
Sympathetic Nervous Activity ◽  
Receptor Blockade ◽  
Nerve Activity ◽  
Hypotensive Action ◽  
The Central Nervous System ◽  
Sympathetic Nervous ◽  
Β Receptor

1. Intravenous infusion of propranolol (3·86 μmol h—1 kg—1) for 2 h lowered arterial pressure in the conscious rabbit whereas similar infusions of practolol (37·6 μmol h—1 kg—1) did not. 2. The fall in blood pressure produced by propranolol was accompanied by a decrease in splanchnic nerve activity. Practolol did not change splanchnic nerve activity. 3. A centrally mediated decrease in sympathetic nervous activity makes an important contribution to the hypotensive action of propranolol in the rabbit. This effect is not shown by practolol.

scholarly journals Immunometabolism and metainflammation in obesity

2020 ◽  
Vol 16 (4) ◽  
pp. 3-17 ◽  
Author(s):  
Tatiana R. Romantsova ◽  
Yulia P. Sych
Keyword(s):  
Insulin Resistance ◽  
Immune System ◽  
Metabolic Diseases ◽  
Fat Cells ◽  
Peripheral Insulin Resistance ◽  
Obesity Therapy ◽  
Key Factor ◽  
The Central Nervous System ◽  
Cellular Hypoxia

Recent studies have shown that immune system cells take an active part in the regulation of metabolic homeostasis. Disruption of the interaction between the immune system and metabolic processes makes a major contribution to the current epidemic of a number of non-communicable metabolic diseases. Due to central and peripheral insulin resistance, obesity is closely associated with type 2 diabetes mellitus. Many mechanisms are involved in the genesis of insulin resistance including chronic inflammation in metabolically active tissues (adipose tissue, intestines, muscles, pancreas, liver), as well as in the central nervous system. Potential triggers of obesity-induced metainflammation are cellular hypoxia, mechanical stress of the fat cells, excess of free fatty acids and lypopolysaccharides. Weight loss is a key factor to eliminating inflammation and improving tissue insulin sensitivity. This review presents literature data on the mechanisms of metainflammation in obesity. Taking into account the contribution of metainflammation to the pathogenesis of the disease, the possibilities and prospects of obesity therapy are discussed.

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.

Sympathetic nervous activity in carriers of MC4R mutations

2006 ◽  
Vol 114 (S 1) ◽  
Author(s):  
D Heutling ◽  
F Sayk ◽  
C Dodt ◽  
HL Fehm ◽  
A Hinney ◽  
...  
Keyword(s):  
Nervous Activity ◽  
Sympathetic Nervous Activity ◽  
Sympathetic Nervous

Central KATP channels modulate glucose effectiveness in humans and rodents

2020 ◽  
Author(s):  
Ada Admin ◽  
Michelle Carey ◽  
Eric Lontchi-Yimagou ◽  
William Mitchell ◽  
Sarah Reda ◽  
...  
Keyword(s):  
Katp Channel ◽  
Glucose Production ◽  
Katp Channels ◽  
Endogenous Glucose Production ◽  
Elevated Plasma ◽  
Sprague Dawley ◽  
Glucose Effectiveness ◽  
Sprague Dawley Rats ◽  
The Central Nervous System

Hyperglycemia is a potent regulator of endogenous glucose production (EGP). Loss of this ‘glucose effectiveness’ is a major contributor to elevated plasma glucose concentrations in type 2 diabetes (T2D). ATP-sensitive potassium channels (K<sub>ATP</sub> channels) in the central nervous system (CNS) have been shown to regulate EGP in humans and rodents. We examined the contribution of central K<sub>ATP</sub> channels to glucose effectiveness. Under fixed hormonal conditions (‘pancreatic clamp’ studies), hyperglycemia suppressed EGP by ~50% in both non-diabetic humans and normal Sprague Dawley rats. By contrast, antagonism of K<sub>ATP</sub> channels with glyburide significantly reduced the EGP-lowering effect of hyperglycemia in both humans and rats. Furthermore, the effects of glyburide on EGP and gluconeogenic enzymes in rats were abolished by intracerebroventricular (ICV) administration of the KATP channel agonist diazoxide. These findings indicate that about half of EGP suppression by hyperglycemia is mediated by central K<sub>ATP</sub> channels. These central mechanisms may offer a novel therapeutic target for improving glycemic control in T2D.

Mutations of mtDNA in some vascular and metabolic diseases

2020 ◽  
Vol 26 ◽  
Author(s):  
Margarita A. Sazonova ◽  
Anastasia I. Ryzhkova ◽  
Vasily V. Sinyov ◽  
Marina D. Sazonova ◽  
Tatiana V. Kirichenko ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Coronary Heart Disease ◽  
Type 2 Diabetes Mellitus ◽  
Heart Disease ◽  
Chronic Diseases ◽  
Metabolic Diseases ◽  
Present Review ◽  
Mtdna Mutations

Background: The present review article considers some chronic diseases of vascular and metabolic genesis, the causes of which may be mitochondrial dysfunction. Very often, in the long course of the disease, complications may occur, leading to myocardial infarction or ischemic stroke and as a result, death.In particular, a large percentage of human deaths nowadays belongs to cardiovascular diseases such as coronary heart disease (CHD), arterial hypertension, cardiomyopathies and type 2 diabetes mellitus. Objective: The aim of the present review was the analysis of literature sources, devoted to an investigation of a link of mitochondrial DNA mutations with chronic diseases of vascular and metabolic genesis, Results: The analysis of literature indicates the association of the mitochondrial genome mutations with coronary heart disease, type 2 diabetes mellitus, hypertension and various types of cardiomyopathies. Conclusion: The detected mutations can be used to analyze the predisposition to chronic diseases of vascular and metabolic genesis. They can also be used to create molecular-cell models necessary to evaluate the effectiveness of drugs developed for treatment of these pathologies. MtDNA mutations associated withthe absence of diseases of vascular and metabolic genesis could be potential candidates for gene therapy of diseases of vascular and metabolic genesis.

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