Pilar Yubero

Oral gavage of oleoyl-oestrone has a stronger effect on body weight in male Zucker obese rats than in female.

This study was carried out to determine the effect of sex and oral administration of oleoyl‐oestrone on body weight of 12‐week‐old female and male Zucker obese (fa/fa) rats initially weighing 350–380 g and 405–420 g, respectively. The rats were maintained in standard conditions and given a daily oral gavage of 0.2 ml oleoyl‐oestrone dissolved in sunflower oil at a dose of 10 μmol/kg/day for 10 days, and their body weight and food intake was monitored. They were then killed, and their carcass composition (water, lipid, protein and total energy), liver lipids and glycogen and plasma chemistry, insulin, free and total oestrone were measured. Oral administration of oleoyl‐oestrone via gavage resulted in significant losses of fat, energy and–ultimately–weight. Treatment with oleoyl‐oestrone decreased food intake; the energy expenditure was kept close to that of controls at the expense of internal fat stores. Nevertheless, body protein and plasma metabolite homeostasis were preserved. The slimming effects were more marked in males than in females. Treatment increased circulating acyl‐oestrone and reduced to normal levels the high insulin observed in controls. Treatment of genetically obese rats with a daily oral gavage of oleoyl‐oestrone resulted in the loss of fat reserves with little modification of other metabolic parameters, except for lower plasma glucose and insulin levels. The results suggest that oleoyl‐oestrone, in addition to its slimming effects may be effective as an antidiabetic agent in type 2 diabetes.

Lithium inhibits brown adipocyte differentiation

Lithium impairs the appearance of the characteristic morphology of brown adipocytes and downregulates the expression of marker genes of brown adipocyte differentiation. These effects are dose‐dependent and are more pronounced when exposure of preadipocytes to lithium is initiated at early stages of differentiation. Although lithium reduces the expression of genes common to both white and brown adipocytes [fatty acid binding protein aP2 (aP2/FABP) or peroxisome proliferating activated receptor γ], genes expressed differentially in brown adipocytes, i.e., uncoupling protein 1, PPAR gamma coactivator‐1α, and peroxisome proliferating activated receptor α, are particularly sensitive to lithium treatment‐dependent downregulation. Brown adipocytes appear as preferential targets of the inhibitory action of lithium on adipocyte differentiation.

Changes in UCP expression in tissues of Zucker rats fed diets with different protein content.

The effect of dietary protein content on the uncoupling proteins (UCP) 1, 2 and 3 expression in a number of tissues of Zucker lean and obese rats was studied. Thirty-day-old male Zucker lean (Fa/?) and obese (fa/fa) rats were fed on hyperproteic (HP, 30% protein), standard (RD, 17% protein) or hypoproteic (LP, 9% protein) dietsad libitum for 30 days. Although dietary protein intake affected the weights of individual muscles in lean and obese animals, these weights were similar. In contrast, huge differences were observed in brown adipose tissue (BAT) and liver weights. Lean rats fed on the LP diet generally increased UCP expression, whereas the HP group had lower values. Obese animals, HP and LP groups showed higher UCP expression in muscles, with slight differences in BAT and lower values for UCP3 in subcutaneous adipose tissue. The mean values of UCP expression in BAT of obese rats were lower than in their lean counterpart, whereas the expression in skeletal muscle was increased. Thus, expression of UCPs can be modified by dietary protein content, in lean and obese rats. A possible thermogenic function of UCP3 in muscle and WAT in obese rats must be taken into account.ResumenSe determina el efecto de cambios moderados en el contenido proteico de la dieta sobre la expresión de las proteínas desacoplantes 1, 2 y 3 en distintos tejidos de la rata Zucker. A ratas Zucker macho de 30 días de edad, tanto delgadas (Fa/?) como obesas (fa/fa), se les administraad libitum una dieta hiperproteica (HP, 30% de contenido proteico), estándar (RD, 17% de contenido proteico) o hipoproteica (LP, 9% de contenido proteico) durante 30 días. Los pesos de los músculos individuales son similares en los animales delgados y en los obesos, aunque ligeramente influenciados por el tipo de dieta; este hecho contrasta con las grandes diferencias detectadas en el hígado y en el tejido adiposo marrón. Los animales delgados alimentados con dieta LP incrementan la expresión de las UCP, mientras que los alimentados como dieta HP muestran valores más bajos. Los animales obesos, tanto los alimentados con dieta LP como con dieta HP, muestran una mayor expresión de UCP en músculo, con pequeñas diferencias en el tejido adiposo marrón y valores muy bajos para la UCP3 en el tejido adiposo subcutáneo. Los valores promedio de la expresión de UCP en el tejido adiposo marrón de las ratas obesas son menores de los de las ratas delgadas, mientras que la expresión en los músculos es superior. Así, la expresión de las UCP puede ser modificada por la ingesta crónica de dietas con dstinto contenido proteico, tanto en ratas delgadas como obesas. Se debe considerar el posible papel termogénico de la UCP3 en el músculo y en el tejido adiposo blanco de las ratas obesas.

Modulation of muscle UCP expression by oleoyl-estrone in the rat

The aim of this study was to determine wether the maintenance of thermogenesis induced by oleoyl-estrone was mediated by modulation of the expression of UCPs. Female adult Zucker lean rats(220-230 g) were used. Osmotic minipumps were inserted under the skin on the rats and connected to the left jugular vein. They delivered a lipid dropled suspension containing oleoyl-estrone (3.5 mmol/kg day, treated) or only the vehicle (control animals). Two weeks after the implantation of the pumps, samples of interscapular brown adipose tissue (BAT) and muscles extensor digitorum longus, tibialis anterior and soleus were obtained and UCP1, UCP2 and UCP3 mRNAs determined by Northern blot. Oleoyl-estrone treatment does not modify UCP1 or UCP2 expression and provokes significant changes in UCP3 expression: increases in BAT and the red-fibre soleus muscle, decreases in the white and red-fibre tibialis anterior muscle and remains unchanged in the white- fibre extensor digitorum longus muscle.