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Overweight and obesity are associated with severe metabolic disorders and an increased risk of cardiovascular diseases. It is a known fact that physical activity has a positive effect on metabolic parameters, and also reduces the risk of diseases such as diabetes. Some products can enhance the rate of lipolysis and help in improving fat loss. One of these are selective androgen receptor modulators (SARMs) which act as anabolic agents and are also believed to aid in fatburning. In this study, we investigated whether 30 days of ostarine administration could potentially improve metabolic parameters using the rat model of obesity combined with exercise. We assessed the levels of biochemical and hormonal parameters in serum samples as well as insulin sensitivity indices of tissues. There were significant changes in the metabolic parameters with exercise. However, we did not find any additive effects of ostarine and exercise on most of the parameters tested. Similar results were obtained from the analysis of gene expression and the concentration of leptin and adiponectin. Our results indicated that ostarine had a lowering effect on cholesterol concentration in the serum (P<0.05). Moreover, when combining ostarine and exercise, additive changes were only observed in the levels of total and HDL cholesterol. No significant change was observed in the metabolic parameters of obese rats with the use of ostarine at the dose of 0.4 mg/kg body weight. Since ostarine is known to enhance performance, further research on its effects is needed. [ABSTRACT FROM AUTHOR]

Synthetic ligands of androgen receptor (AR) are a standard in the treatment of androgen deficiency. One of the effects of androgen deficiency is the disturbance in the homeostasis of lipid metabolism. Till date, there are no effective compounds developed to treat androgen deficiency without having any side effects. Nonsteroidal selective androgen receptor modulators (SARMs) are a promising solution for various clinical indications. In this study, we investigated the effect of ostarine (enobosarm), a nonsteroidal SARM, on the rat adipocyte metabolism using in vitro techniques. Isolated rat adipocytes were incubated in the presence of different concentrations of ostarine. Control incubation with testosterone as the natural ligand for AR was performed. AR inhibitors were used to investigate the genomic activity of ostarine. Changes in the intensity of lipolysis, lipogenesis, and the secretion of leptin and adiponectin were measured. Moreover, the gene expression of leptin and adiponectin was assessed. For the first time, we have shown that ostarine has a significant effect on the intensity of lipid metabolism. Ostarine downregulates the expression of leptin and adiponectin mRNAs, as well as decreases their release from rat adipocytes. According to our results, ostarine acts via AR with a similar effect as testosterone in the regulation of lipid metabolism and endocrine function of mature rat adipocytes in vitro. Our results indicate the need for further studies on the effects of SARM on the whole organism. [ABSTRACT FROM AUTHOR]

Aging is associated with insulin resistance but the exact molecular mechanism is still unknown. Tissue insulin resistance can be evoked by the decreased sensitivity to insulin, the decreased responsiveness to hormone or both. As the first step in insulin action is its binding to alfa subunits of the receptor we, therefore, studied the insulin binding kinetics in plasma membranes of the liver, heart and skeletal muscle in order to establish whether their ability to bind the hormone is altered with aging. Plasma membranes were prepared and purified according to Havrankowa and binding assay was performed using (125I)-iodoinsulin. The kinetic parameters of the hormone-receptor interaction were analysed by the method of Scatchard using the LIGAND-Pc v.3.1. computer program. The binding potency of insulin was calculated as IC50 using ALLFIT-Pc v.2.7. computer program. We have shown that there are striking differences in insulin binding kinetics in newborn and old rats, depending on kind of tissue tested. The liver plasma membranes ability for insulin binding, number of high (HAIR) and low (LAIR) affinity insulin receptors, values of the dissociation constants and products of association constants and number of insulin receptors, were almost the same, being not dependent on age of the rats. By contrast, there is less high affinity insulin receptors in skeletal muscle of the old animals. The most dramatic changes in insulin binding occur in the heart where both high and low affinity insulin receptors are greatly affected by aging. Our results indicate that the response of the three tissues tested to hyperglycemia and hyperinsulinemia, observed in the old rats, has not been identical and probably can be accounted for by the different distribution of insulin receptor isoforms in the liver, heart and skeletal muscles as shown recently by Vidal et al.

The first step in insulin action is its specific binding to alpha-subunits of the receptor in the plasma membrane. Rats of Wistar strain are commonly used as laboratory animals but there are no data comparing insulin binding by various rat tissues. We studied the insulin binding kinetics in plasma membranes isolated from hearts, livers, brains, skeletal muscles, adipose tissue, thymus and testes in order to compare their ability to bind 125I-insulin and to test which membrane preparation is most useful and convenient for such a study. The dissociation constant (Kd) and the quantity of receptors measured as a binding capacity were determined by the Scatchard method using the LIGAND computer program whereas the binding potency of insulin was calculated as IC50 using the ALLFIT computer program. We also introduced the product of Ka x R50 (affinity constant multiplied by binding capacity) as an index which describes the functional features of insulin receptors taking into account both number of insulin receptors and their affinity. Taking all the parameters of insulin binding tested together we can conclude that the liver and, to some extent, adipose tissue may provide a useful model for studying hormone-receptor interaction. By contrast, to the group of rat tissues responding rather poorly to insulin belong thymus and testis.

The aim of the study was to investigate the effect of hypothermia on (125J)-insulin binding to rat skeletal muscle membranes and to determine whether the decrease in blood insulin concentration could be related to changes in the number or in the affinity of insulin receptor sites according to the down-regulation theory. Rat skeletal muscle membranes were prepared from control, normothermic rats (Tr = 35.6 +/- 0.3 degree C) and hypothermic rats (Tr = 26.0 +/- 0.5 degree C) and purified according to Havrankowa. In order to determine the kinetic parameters of the hormone-receptor interaction the data from the competition binding studies were analysed by the method of Scatchard using the LIGAND Pc.v.3.1. computer program of Munson and Rodbard. We have shown that under hypothermic conditions insulin receptors number is significantly increased in specific hindlimb skeletal muscles but the changes take place mainly in the low affinity receptors class. The phenomenon probably results from the lack of spare high affinity insulin receptors in skeletal muscle as shown recently by Camps et al.

The aim of the study was to compare the number and affinity of insulin receptors in adipose tissue of both normothermic and hypothermic rats. Plasma membranes from epididymal adipose tissue were prepared and purified according to Havrankowa and binding assay was performed using (125I)-iodoinsulin. The kinetic parameters of the hormone-receptor interaction were analysed by the method of Scatchard using the LIGAND--Pc v.3.1. computer program of Munson and Rodbard. The binding potency of insulin was calculated as IC50 using the ALLFIT--Pc v. 2.7. computer program. Maximum specific insulin binding to plasma membranes in adipose tissue was decreased in the hypothermic rats but half-maximum displacement of tracer insulin was similar in the normothermic and hypothermic group suggesting that reduced receptor numbers rather than reduced affinity accounted for the difference.

D,L-arginine and L-lysine, introduced into the alimentary canal (IAC), caused significant secretion of insulin in rabbits, whereas D,L-methionine or L-phenylalanine evoked only a small effect. Also, intravenous (IV) injection of D,L-arginine caused dose dependent and biphasic insulin output. On the other hand, L-phenylalanine given IV decreased both basal and glucose--stimulated insulin level in blood.