The Journal of endocrinology
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Acute critically ill patients experience a rapid decline in plasma free thyroid hormone levels (free triiodothyronine (FT3) and free levothyroxine (FT4)), with a marked elevation of reverse T3, recognized as the euthyroid sick syndrome (ESS) or low-T3 syndrome. The ESS is also often associated with depressed myocardial function, sometimes referred to as the 'stunned myocardium'. Its clinical effects may vary from minimal hemodynamic impairment to cardiogenic shock. ⋯ There is an inability to generate ATP through the Krebs cycle, which reduces the high-energy phosphate pool essential for all cell ATPases. Under all three conditions, following administration of T3/T4, the myocardial dysfunction was rapidly reversed. We, therefore, cautiously advocate the use of thyroid hormonal therapy to any patient with the ESS and/or a stunned myocardium.
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In association with sleep-wake and fasting-feeding cycles, organisms experience dramatic oscillations in energetic demands and nutrient supply. It is therefore not surprising that various metabolic parameters, ranging from the activity status of molecular energy sensors to circulating nutrient levels, oscillate in time-of-day-dependent manners. ⋯ By synchronizing the cell with its environment, clocks modulate a host of metabolic processes in a temporally appropriate manner. The purpose of this article is to review current understanding of the interplay between circadian clocks and metabolism, in addition to the pathophysiologic consequences of disruption of this molecular mechanism, in terms of cardiometabolic disease development.
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The discovery of irisin as an exercise-regulated myokine inducing browning of WAT has gained interest as a potential new strategy to combat obesity and its associated disorders, such as type 2 diabetes. However, there are inconsistencies regarding the relevance of irisin in humans. The regulation of FNDC5 mRNA expression by exercise and contraction could not be reproduced by a number of human studies using several exercise protocols and in vitro approaches. ⋯ Independent of the presence and regulation of FNDC5/irisin in humans, the application of recombinant irisin could still represent a therapeutic strategy to fight obesity. However, the current data obtained from human cell models reveal that FNDC5/irisin has no effect on browning of the major WAT depots in humans and is likely to selectively target a small subpopulation of adipocytes, which are located in classical BAT regions, such as the supraclavicular adipose tissue. Thus, other candidates, such as BMP7 or CNPs, seem to be more prominent candidates as inducers of browning in humans.
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Metabolic profiling, or metabolomics, has developed into a mature science in recent years. It has major applications in the study of metabolic disorders. This review addresses issues relevant to the choice of the metabolomics platform, study design and data analysis in diabetes research, and presents recent advances using metabolomics in the identification of markers for altered metabolic pathways, biomarker discovery, challenge studies, metabolic markers of drug efficacy and off-target effects. The role of genetic variance and intermediate metabolic phenotypes and its relevance to diabetes research is also addressed.
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The renin-angiotensin system (RAS) plays a crucial role in the regulation of physiological homeostasis and diseases such as hypertension, coronary artery disease, and chronic renal failure. In this cascade, the angiotensin-converting enzyme (ACE)/angiotensin II (Ang II)/AT1 receptor axis induces pathological effects, such as vasoconstriction, cell proliferation, and fibrosis, while the ACE2/Ang-(1-7)/Mas receptor axis is protective for end-organ damage. The altered function of the RAS could be a contributing factor to the cardiac and renal alterations induced by GH excess. ⋯ Importantly, the levels of ACE2, Ang-(1-7), and Mas receptor were markedly decreased in both tissues. In addition, Ang-(1-7) administration reduced SBP to control values in GH-transgenic mice, indicating that the ACE2/Ang-(1-7)/Mas axis is involved in GH-mediated hypertension. The data indicate that the altered expression profile of the ACE2/Ang-(1-7)/Mas axis in the heart and the kidney of bGH mice could contribute to the increased incidence of hypertension, cardiovascular, and renal alterations observed in these animals.