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 Roles of Beta2- and Beta3-Adrenoceptor Polymorphisms in Hypertension and Metabolic Syndrome

2010 ◽  
Vol 2010 ◽  
pp. 1-12 ◽  
Author(s):  
Kazuko Masuo
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Nervous System ◽  
Sympathetic Nervous System ◽  
Vascular Reactivity ◽  
Resting Metabolic Rate ◽  
Sympathetic Nervous ◽  
Obesity Hypertension ◽  
Sympathetic Nerve Activation

Hypertension, diabetes mellitus (especially type 2 diabetes mellitus), metabolic syndrome and obesity are rapidly growing public health problems. Sympathetic nerve activation is observed in obesity, hypertension and diabetes mellitus, which 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 have been mainly mediated via the 2- and 3-adrenergic receptors in humans. Further, 2-adrenoceptors importantly influence vascular reactivity and may regulate blood pressure. Genetic polymorphistns of the -adrenoceptor gene have been shown to alter the function of several adrenoceptor subtypes and thus to modify the response to catecholamine. 2-adrenoceptor polymorphisms (Arg16Gly, Gln27Glu, and Thr164Ile) have been studied in relation to hypertension. Genetic variations in the 3-adrenoceptor (i.e. Try64Arg variant) are also associated with both obesity and hypertension. However, the precise relationships of the polymorphisms of 2- and 3-adrenoceptor genes with sympathetic nervous system activity, hypertension, and metabolic syndrome have not been fully clarified. This paper will discuss the current topics involving the influence of the sympathetic nervous system and 2- and 3- adrenoceptor polymorphisms in hypertension and metabolic syndrome.

scholarly journals Leptin Enhances Insulin Sensitivity by Direct and Sympathetic Nervous System Regulation of Muscle IGFBP-2 Expression: Evidence From Nonrodent Models

Endocrinology ◽  
2014 ◽  
Vol 155 (6) ◽  
pp. 2133-2143 ◽  
Author(s):  
Steven W. Yau ◽  
Belinda A. Henry ◽  
Vincenzo C. Russo ◽  
Glenn K. McConell ◽  
Iain J. Clarke ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Nervous System ◽  
Insulin Sensitivity ◽  
Sympathetic Nervous System ◽  
Insulin Signaling ◽  
In Vivo Experiments ◽  
Sympathetic Nervous

Leptin is produced from white adipose tissue and acts primarily to regulate energy balance. Obesity is associated with leptin resistance and increased circulating levels of leptin. Leptin has recently been shown to influence levels of IGF binding protein-2 (IGFBP-2), a protein that is reduced in obesity and type 2 diabetes. Overexpression of IGFBP-2 protects against obesity and type 2 diabetes. As such, IGFBP-2 signaling may represent a novel pathway by which leptin regulates insulin sensitivity. We sought to investigate how leptin regulates skeletal muscle IGFBP-2 levels and to assess the impact of this on insulin signaling and glucose uptake. In vitro experiments were undertaken in cultured human skeletal myotubes, whereas in vivo experiments assessed the effect of intracerebroventricular leptin on peripheral skeletal muscle IGFBP-2 expression and insulin sensitivity in sheep. Leptin directly increased IGFBP-2 mRNA and protein in human skeletal muscle through both signal transducer and activator of transcription-3 and phosphatidylinositol 3-kinase signaling, in parallel with enhanced insulin signaling. Silencing IGFBP-2 lowered leptin- and insulin-stimulated protein kinase B phosphorylation and glucose uptake. In in vivo experiments, intracerebroventricular leptin significantly increased hind-limb skeletal muscle IGFBP-2, an effect completely blocked by concurrent peripheral infusion of a β-adrenergic blocking agent. Sheep receiving central leptin showed improvements in glucose tolerance and circulating insulin levels after an iv glucose load. In summary, leptin regulates skeletal muscle IGFBP-2 by both direct peripheral and central (via the sympathetic nervous system) mechanisms, and these likely impact on peripheral insulin sensitivity and glucose metabolism.

Catestatin as a regulator of sympathetic nervous system activity and its influence on the development and progression of arterial hypertension and type 2 diabetes mellitus

2021 ◽  
Vol 42 (2) ◽  
pp. 49-54
Author(s):  
O. А. Pankova ◽  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Nervous System ◽  
Type 2 Diabetes Mellitus ◽  
Sympathetic Nervous System ◽  
Arterial Hypertension ◽  
Nicotinic Acetylcholine Receptors ◽  
Potential Biomarker ◽  
Sympathetic Nervous

The article analyzes the results of conducted studies about the effect of catestatin on the development of arterial hypertension and type 2 diabetes mellitus, since hyperactivation of the sympathetic nervous system is a powerful pathogenetic mechanism of their progression. This paper considers the causes of increased secretion and release of catecholamines due to the activity of the sympathetic nervous system and its impact on the reduction of catestatin levels, which has an inhibitory effect blocking nicotinic acetylcholine receptors. Non-synonymous single nucleotide polymorphisms of the catestatin domain Gly364Ser, Pro370Leu, Arg374Gln, Gly367Val and the difference of their antiadrenergic activity in comparison with the wild type of catestatin are studied, the reasons of changes in the efficiency of catestatin alleles are determined. It is estimated the pathogenetic significance of low levels of catestatin in the development of hypertension through the mechanisms of impaired vasodilation and inhibition of catecholamines. The predictive significance of catestatin is based on decrease in its level in persons with hereditary predisposition to the development of arterial hypertension. The anti-inflammatory effect of catestatin determines its role in the pathogenesis of diseases accompanied by chronic inflammation, including type 2 diabetes mellitus and atherosclerosis. The role of catestatin in the regulation of glucose metabolism due to an insulin-like effect and inhibition of glucose secretion by hepatocytes, as well as improving glucose tolerance and insulin sensitivity, has been established. The perspectives of catestatin are determined as a potential biomarker of arterial hypertension and type 2 diabetes mellitus.

The Influence of Obesity in Hypertension

Physiology ◽  
1990 ◽  
Vol 5 (6) ◽  
pp. 245-249 ◽  
Author(s):  
AP Rocchini
Keyword(s):  
Nervous System ◽  
Cardiac Output ◽  
Sympathetic Nervous System ◽  
Combined Effects ◽  
Sodium Retention ◽  
Sympathetic Nervous System Activity ◽  
Concomitant Increase ◽  
Nervous System Activity ◽  
Sympathetic Nervous ◽  
Obesity Hypertension

Data are presented to suggest that obesity hypertension is primarily related to increased sodium retention and a concomitant increase in cardiac output. Evidence is also summarized suggesting sodium retention is due to combined effects of hyperinsulinemia, hyperaldosteronism, and/or increased sympathetic nervous system activity.

scholarly journals Type-2 Iodothyronine 5′Deiodinase (D2) in Skeletal Muscle of C57Bl/6 Mice. II. Evidence for a Role of D2 in the Hypermetabolism of Thyroid Hormone Receptor α-Deficient Mice

Endocrinology ◽  
2011 ◽  
Vol 152 (8) ◽  
pp. 3093-3102 ◽  
Author(s):  
W. Ramadan ◽  
A. Marsili ◽  
P. R. Larsen ◽  
A. M. Zavacki ◽  
J. E. Silva
Keyword(s):  
Skeletal Muscle ◽  
Nervous System ◽  
Thyroid Hormone ◽  
Sympathetic Nervous System ◽  
Wild Type ◽  
High Fat ◽  
Consistent Finding ◽  
Alternate Form ◽  
Sympathetic Nervous

Mice with ablation of the Thra gene have cold intolerance due to an as yet undefined defect in the activation of brown adipose tissue (BAT) uncoupling protein (UCP). They develop an alternate form of facultative thermogenesis, activated at temperatures below thermoneutrality and associated with hypermetabolism and reduced sensitivity to diet-induced obesity. A consistent finding in Thra-0/0 mice is increased type-2 iodothyronine deiodinase (D2) mRNA in skeletal muscle and other tissues. With an improved assay to measure D2 activity, we show here that this enzyme activity is increased in proportion to the mRNA and as a function of the ambient cold. The activation is mediated by the sympathetic nervous system in Thra-0/0, as it is in wild-type genotype mice, but the sympathetic nervous system effect is greater in Thra-0/0 mice. Using D2-ablated mice (Dio2−/−), we reported elsewhere and show here that, in spite of sharing a severe deficiency in BAT thermogenesis with Thra-0/0 and UCP1-knockout mice, they do not have an increase in oxygen consumption, and they gain more weight than wild-type controls when fed a high-fat diet. UCP3 mRNA is highly responsive to thyroid hormone, and it is increased in Thra-0/0 mice, particularly when fed high-fat diets. We show here that muscle UCP3 mRNA in hypothyroid Thra-0/0 mice is responsive to small dose-short regimens of T4, indicating a role for locally, D2-generated T3. Lastly, we show that bile acids stimulate not only BAT but also muscle D2 activity, and this is associated with stimulation of muscle UCP3 mRNA expression provided T4 is present. These observations strongly support the concept that enhanced D2 activity in Thra-0/0 plays a critical role in their alternate form of facultative thermogenesis, stimulating increased fat oxidation by increasing local T3 generation in skeletal muscle.

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