scholarly journals The Role of Non-Aromatizable Testosterone Metabolite in Metabolic Pathways

2011 ◽  
pp. 253-261 ◽  
Author(s):  
M. DUŠKOVÁ ◽  
H. POSPÍŠILOVÁ

Dihydrotestosterone (DHT) originates via irreversible reduction of testosterone by catalytic activity of 5α-reductase enzyme and it is demonstratively the most effective androgen. Androgens influence adipose tissue in men either directly by stimulation of the androgen receptor or indirectly, after aromatization, by acting at the estrogen receptor. DHT as a non-aromatizable androgen could be responsible for a male type fat distribution. The theory of non-aromatizable androgens as a potential cause of a male type obesity development has been studied intensively. However, physiological levels of DHT inhibit growth of mature adipocytes. In animal models, substitution of DHT in males after gonadectomy has a positive effect on body composition as a testosterone therapy. Thus, DHT within physiological range positively influences body composition. However, there are pathological conditions with an abundance of DHT, e.g. androgenic alopecia and benign prostatic hyperplasia. These diseases are considered as risk factors for development of metabolic syndrome or atherosclerosis. In obese people, DHT metabolism in adipose tissue is altered. Local abundance of non-aromatizable androgen has a negative effect on adipose tissue and it could be involved in pathogenesis of metabolic and cardiovascular diseases. Increased DHT levels, compared to physiological levels, have negative effect on development of cardiovascular diseases. Difference between the effect of physiological and increased level brings about certain paradox.

Author(s):  
Teruhide Koyama ◽  
Nagato Kuriyama ◽  
Ritei Uehara

Background: The aim of this study was to investigate whether plasma midregional proadrenomedullin (MR-proADM) reflected body composition, such as body mass index (BMI), visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), VAT/SAT ratio, body fat mass (BFM), and skeletal muscle mass (SMM). Methods: A total of 2244 individuals (727 men and 1517 women) were included in the study. Multiple regression analysis was performed to assess the combined influence of variables: age, daily alcohol consumption, Brinkman index, sleeping time, metabolic equivalents, anamnesis for hypertension, dyslipidemia, diabetes, and body composition of MR-proADM, by using a stepwise forward selection method. Results: MR-proADM was significantly related to all anthropometric indices (BMI, VAT, SAT, VAT/SAT ratio, BFM, and SMM) in men and women. On the basis of a stepwise forward selection method, VAT (men: beta = 0.184, p < 0.001, women: beta = 0.203, p < 0.001) and BFM (beta = 0.181, p < 0.001) in women, were found to be significantly associated with MR-proADM. Conclusion: This study suggests that plasma MR-proADM concentration is a more reliable indicator of VAT for fat distribution, and thus, MR-proADM may help better understand the obesity paradox. Changes in circulating levels of MR-proADM could possibly reflect changes in body composition, endocrine, and metabolic milieu.


Author(s):  
Hubert Mado ◽  
Wioletta Szczurek ◽  
Mariusz Gąsior ◽  
Bożena Szyguła-Jurkiewicz

The adipose tissue, apart from storing energy, plays a role of an endocrine organ. One of the most important adipokines secreted by adipose tissue is adiponectin, which is also produced by cardiomyocytes and connective tissue cells within the heart. Adiponectin is known for its beneficial effect on the metabolism and cardiovascular system and its low level is a factor of development of many cardiovascular diseases. Paradoxically, in the course of heart failure, adiponectin level gradually increases with the severity of the disease and higher adiponectin level is a factor of poor prognosis. As a result, there is a growing interest in adiponectin as a marker of heart failure progression and a predictor of prognosis in the course of this disease.


2009 ◽  
Vol 54 (4) ◽  
pp. 313-320 ◽  
Author(s):  
Idoia Labayen ◽  
Francisco B. Ortega ◽  
Luis A. Moreno ◽  
Carlos Redondo-Figuero ◽  
Gloria Bueno ◽  
...  

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Julia H. Goedecke ◽  
Naomi S. Levitt ◽  
Juliet Evans ◽  
Nicole Ellman ◽  
David John Hume ◽  
...  

Women of African ancestry, particularly those living in industrialized countries, experience a disproportionately higher prevalence of type 2 diabetes (T2D) compared to their white counterparts. Similarly, obesity and insulin resistance, which are major risk factors for T2D, are greater in black compared to white women. The exact mechanisms underlying these phenomena are not known. This paper will focus on the role of adipose tissue biology. Firstly, the characteristic body fat distribution of women of African ancestry will be discussed, followed by the depot-specific associations with insulin resistance. Factors involved in adipose tissue biology and their relation to insulin sensitivity will then be explored, including the role of sex hormones, glucocorticoid metabolism, lipolysis and adipogenesis, and their consequent effects on adipose tissue hypoxia, oxidative stress, and inflammation. Finally the role of ectopic fat deposition will be discussed. The paper proposes directions for future research, in particular highlighting the need for longitudinal and/or intervention studies to better understand the mechanisms underlying the high prevalence of insulin resistance and T2D in women of African ancestry.


2010 ◽  
Vol 16 (1) ◽  
pp. 93-103 ◽  
Author(s):  
M. V. Tsvetkova ◽  
V. N. Khirmanov ◽  
N. N. Zybina

The paper reviews publications concerned the role of nonesterifi ed fatty acids (NEFA) in pathogenesis of cardiovascular diseases. NEFAs are four and more carbons chain length carbonic acids and they are presented in free form (nonesterifi ed) in human body. Plasma NEFAs are produced by the adipose tissue triglyceride lipolysis, another source are lipoproteins such as chylomicrons, very low density lipoproteins and intermediate density lipoproteins. Elevated NEFA concentrations in plasma are the risk factor of cardiovascular diseases and type 2 diabetes mellitus and the independent risk factor of hypertension and sudden death. NEFA plasma concentration is elevated in atherosclerosis, acute myocardial infarction, diabetes mellitus, obesity, hypertension, and often in metabolic syndrome. A probable cause of NEFAs accumulation in plasma may be overeating and low physical activity, which result in increase of adipose tissue mass, lipolysis intensifi cation and elevation of NEFAs concentration in plasma. The role of elevated plasma NEFA concentration in a number of conditions (abdominal obesity, atherogenic dyslipidemia, insulin resistance, type 2 diabetes mellitus, endothelial dysfunction, vascular infl ammation, atherosclerosis, hypertension, ischemic heart disease, rhythm disturbances, sudden death) and possible ways of their correction are discussed.


2021 ◽  
Vol 12 ◽  
Author(s):  
Magdalena Czerwińska ◽  
Katarzyna Czarzasta ◽  
Agnieszka Cudnoch-Jędrzejewska

According to the World Health Organization report published in 2016, 650 million people worldwide suffer from obesity, almost three times more than in 1975. Obesity is defined as excessive fat accumulation which may impair health with non-communicable diseases such as diabetes, cardiovascular diseases (hypertension, coronary artery disease, stroke), and some cancers. Despite medical advances, cardiovascular complications are still the leading causes of death arising from obesity. Excessive fat accumulation is caused by the imbalance between energy intake and expenditure. The pathogenesis of this process is complex and not fully understood, but current research is focused on the role of the complex crosstalk between the central nervous system (CNS), neuroendocrine and immune system including the autonomic nervous system, adipose tissue, digestive and cardiovascular systems. Additionally, special attention has been paid to newly discovered substances: neuropeptide 26RFa, preptin, and adropin. It was shown that the above peptides are synthesized both in numerous structures of the CNS and in many peripheral organs and tissues, such as the heart, adipose tissue, and the gastrointestinal tract. Recently, particular attention has been paid to the role of the presented peptides in the pathogenesis of obesity, metabolic and cardiovascular system diseases. This review summarizes the role of newly investigated peptides in the crosstalk between brain and peripheral organs in the pathogenesis of obesity, metabolic, and cardiovascular diseases.


Circulation ◽  
2012 ◽  
Vol 125 (suppl_10) ◽  
Author(s):  
Xiaomin Zhang ◽  
Qibin Qi ◽  
Frank Hu ◽  
Frank Sacks ◽  
Lu Qi

OBJECTIVE The fat mass and obesity-associated gene (FTO) variant has shown the strongest association with obesity. Recent studies suggest that dietary intake may modify the genetic effects of FTO. We tested the effect of FTO variant on long-term weight loss and change in body composition in a 2-year randomized intervention trial. RESEARCH DESIGN AND METHODS FTO SNP rs1558902 was genotyped in 742 overweight or obese adults who were randomly assigned to one of four diets differing in the percentages of energy derived from fat, protein and carbohydrate (20, 15, and 65%; 20, 25, and 55%; 40, 15, and 45%; and 40, 25, and 35%) in the Pounds Lost Trial for 2 years. Body composition and fat distribution were measured in 424 and 195 participants by Dual-energy X-ray absorptiometry (DXA) and computed tomography (CT), respectively. RESULTS We found significant modification effects for diet intervention varying in protein (low vs high), but not in fat, on 2-year changes in total fat, fat free mass (FFM), fat mass% (FM%), trunk fat%, total adipose tissue mass (TAT), visceral adipose tissue mass (VAT) and superficial adipose tissue mass (SAT) (P for interactions=0.045, 0.036, 0.033, 0.048, 0.001, 0.008 and 0.002, respectively). Carriers of the risk allele (A allele) had a greater loss of weight and regional fat in response to high protein diet, while an opposite genetic effect was observed on changes in TAT and SAT in response to low protein diet at 2 years. Significant gene by diet interventions (low vs high protein) were also observed at 6 months of intervention, when the maximum of weight-loss was achieved, for changes in FFM, TAT, VAT and SAT (P for interactions=0.007, 0.019, 0.036 and 0.041, respectively). Patterns of change in body composition and fat distribution by diet intervention were similar at 6 month and 2 year. CONCLUSIONS Our data suggest that a high-protein diet may be beneficial for weight loss in individuals with the risk allele of the FTO variant rs1558902.


Biomedicines ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 184
Author(s):  
Sebastian Dommel ◽  
Claudia Berger ◽  
Anne Kunath ◽  
Matthias Kern ◽  
Martin Gericke ◽  
...  

Developmental genes are important regulators of fat distribution and adipose tissue (AT) function. In humans, the expression of homeobox c9 (HOXC9) is significantly higher in subcutaneous compared to omental AT and correlates with body fat mass. To gain more mechanistic insights into the role of Hoxc9 in AT, we generated Fabp4-Cre-mediated Hoxc9 knockout mice (ATHoxc9-/-). Male and female ATHoxc9-/- mice were studied together with littermate controls both under chow diet (CD) and high-fat diet (HFD) conditions. Under HFD, only male ATHoxc9-/- mice gained less body weight and exhibited improved glucose tolerance. In both male and female mice, body weight, as well as the parameters of glucose metabolism and AT function were not significantly different between ATHoxc9-/- and littermate control CD fed mice. We found that crossing Hoxc9 floxed mice with Fabp4-Cre mice did not produce a biologically relevant ablation of Hoxc9 in AT. However, we hypothesized that even subtle reductions of the generally low AT Hoxc9 expression may cause the leaner and metabolically healthier phenotype of male HFD-challenged ATHoxc9-/- mice. Different models of in vitro adipogenesis revealed that Hoxc9 expression precedes the expression of Fabp4, suggesting that ablation of Hoxc9 expression in AT needs to be achieved by targeting earlier stages of AT development.


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