Biomedical subjects

B Berraondo

Publications and source records attributed to B Berraondo.

5 recordsLinked to original sources

PubMed2000

Free fatty acids are involved in the inverse relationship between hormone-sensitive lipase (HSL) activity and expression in adipose tissue after high-fat feeding or beta3-adrenergic stimulation.

OBJECTIVE: The hormone-sensitive lipase (HSL) is the rate-limiting enzyme in adipose tissue lipolysis. The aim of this experimental trial was to study the effects of a beta3-adrenergic agonist (Trecadrine) on plasma fatty acids, adipocyte HSL activity, and gene expression in control and cafeteria-induced obese animals. RESEARCH METHODS AND PROCEDURES: Control and cafeteria-fed rats were treated with a placebo or Trecadrine during 35 days. Plasma fatty acids were measured by an enzymatic method, whereas HSL activity was assessed by using labeled triolein as substrate. Finally, HSL gene expression from white adipose tissue (WAT) was determined using a reverse transcription-polymerase chain reaction method. RESULTS: Trecadrine administration reduced plasma fatty acids and HSL mRNA levels in abdominal WAT, whereas HSL activity was significantly higher in the Trecadrine-treated obese rats than in the obese nontreated rats. Also, abdominal WAT HSL activity significantly increased, whereas WAT HSL gene expression fell in control rats treated with beta3-adrenergic agonist as compared with control untreated animals. DISCUSSION: In situations of fat accumulation (high-fat feeding) or lipid mobilization (beta3-adrenergic stimulation), changes in HSL activity and HSL gene expression seem to follow a trend related to plasma fatty acids levels, as indicated by the positive correlation (r = 0.39, p < 0.05) between HSL mRNA levels and plasma fatty acids, and the negative correlation (r = -0.38, p < 0.05) between plasma fatty acids and HSL activity. Furthermore, a highly negative correlation (r = -0.59, p < 0.001) between HSL activity and HSL mRNA expression was found, in which plasma-free fatty acids are apparently involved.

Adipose Tissue↗

PubMed2000

Up-regulation of muscle UCP2 gene expression by a new beta3-adrenoceptor agonist, trecadrine, in obese (cafeteria) rodents, but down-regulation in lean animals.

OBJECTIVE: The anti-obesity properties of a new beta3-adrenergic agonist (Trecadrine) were examined in a diet-induced obesity model, including the effects on OB and uncoupling protein (UCP-1 and -2) gene expression. MEASUREMENTS: Control rats and cafeteria-fed rats were treated with placebo or Trecadrine for 35 days. Leptin and UCP (1 and 2) mRNA levels were determined by reverse transcription-polymerase chain reaction (RT-PCR) methodology in adipose tissue and gastrocnemius muscle. RESULTS: Animals fed a cafeteria diet increased body weight, fat content, white adipose tissue (WAT), brown adipose tissue (BAT) weights and oxygen consumption in relation to lean controls. A rise in plasma leptin, WAT OB gene expression as well as circulating free fatty acids levels was found in obese rats as compared with lean controls. Trecadrine administration to cafeteria-fed animals decreased fat content, WAT weight, circulating leptin and fatty acids concentrations, and WAT OB gene expression, reaching comparable values to lean controls, while WAT O2 consumption was increased in these animals. Also, an increase in BAT UCP1 mRNA levels was found through a two-way analysis of variance in control and obese animals after Trecadrine administration. Gastrocnemius muscle UCP2 gene expression was reduced in lean Trecadrine-treated and diet-induced obese animals as compared to controls, while an increase was found in cafeteria-fed animals after Trecadrine administration. A negative correlation between WAT O2 consumption and UCP2 expression was found in control animals, but not in the cafeteria-fed groups, suggesting a differential response to the beta3-adrenergic compound in lean and obese animals, which is in agreement with the reported statistical interactions between obesity and Trecadrine administration found for WAT O2 consumption and muscle UCP2 expression, as well as for plasma leptin and WAT leptin expression. CONCLUSION: The new beta3-adrenergic agonist, Trecadrine, decreases fat content and increases gastrocnemius muscle UCP2 gene expression in a diet-induced obesity model. This sheds additional light on the action mechanism of compounds with affinity for beta3-adrenoceptors and other potential anti-obesity agents.

Adipose Tissue↗

PubMed1999

Hypolipidemic properties of a diphenyl-methylen-ethylamine derivative with affinity for beta 3-adrenoceptors in a model of hypercholesterolemia.

beta 3-Adrenergic agonists have been proposed as potential new drugs for the treatment of diabetes and/or obesity therapy, because of the hypoglycemic and lipolytic effects found with some of these compounds. Moreover, their application in other therapeutic areas such as hypercholesterolemia and atherosclerosis has been suggested. This experimental trial was conducted to assess the effects of Trecadrine, a new molecule with affinity for beta 3-adrenoceptors, on a model of hypercholesterolemia in rats, and also to explore a possible beneficial role of these agents in lipid disturbances therapy. The results indicated a marked reduction in serum triglyceride levels (-40%; P < 0.01) and lipoprotein lipase activity in white fat (-49%, P < 0.001) of hypercholesterolemic rats treated with Trecadrine for 16 days as compared with hypercholesterolemic non-treated rats. Moreover, Trecadrine produced a significant increase in the oxygen consumption in brown adipose tissue (+154%, P < 0.01). In relation to cholesterolemia, an improvement in total cholesterol (-20%) and total/HDL-cholesterol ratio (-25%) in serum was noted in the animals receiving the pharmacological treatment. In conclusion, the results of this trial support that Trecadrine administration may have a therapeutic potential in disorders associated with hypertriglyceridemia such as obesity and some types of hyperlipidaemias.

Adrenergic beta-Agonists↗

PubMed1999

Leptin: physiological actions.

Leptin, a peptide hormone (167 aa) mainly expressed in adipocytes, and its hypothalamic receptors are integral components of a complex physiological system evolved to regulate fuel stores and energy expenditure. Thus, leptin discovery has constituted a great breakthrough in the understanding of body weight regulation and in the role of the fat tissue as an endocrine organ. Increasing scientific evidences suggest that, leptin has overall effects on metabolism. Leptin mRNA and/or protein are produced by placenta, fetal tissues, gastric mucosa and hepatic stellate cells and can participate in many physiological functions such as fetal growth, gut-derived satiety, immune or proinflammatory responses, reproduction, nutrient intestinal absorption, angiogenesis and lipolysis. The leptin participation in body weight homeostasis and obesity as well as other peripheral actions are revisited.

Animals↗

PubMed1997

Effects of trecadrine, a beta 3-adrenergic agonist, on intestinal absorption of D-galactose and disaccharidase activities in three physiopathological models.

Impairments in intestinal absorptive and digestive processes have been described in several pathophysiological situations, such as in drug-induced diabetes, obesity and hypercholesterolaemia. Furthermore, there is evidence for the occurrence of beta 3-adrenoceptors in multiple regions of the gastrointestinal tract, but there are no data concerning their possible involvement on jejunal and ileal digestive and absorptive functions. In this work, we have measured the modifications of selective intestinal absorption and disaccharidase activities in alloxan-induced diabetic and in diet-induced obese and hypercholesterolaemic Wistar rats. The action of a beta 3-adrenergic agonist (Trecadrine) with hypoglycaemic and lipolytic properties on those gastrointestinal functions has been studied. Increases in the galactose uptake by intestinal rings and in both sucrase and maltase activities were found in diabetic rats. The results obtained after Trecadrine administration to diabetic rats led to an improvement of the altered values. On the other hand, our data show a decrease in sugar absorption and in disaccharidase activities in both obese and hypercholesterolaemic groups, probably related to the low carbohydrate and high fat content of these diets. An amelioration in sucrase activity was observed after treatment with Trecadrine. Finally, Trecadrine administration to control animals significantly inhibited galactose intestinal absorption, which was independently confirmed by additional in-vitro studies. Overall, these results could be attributed not only to an improvement in the pathophysiological condition (diabetes, obesity and hypercholesterolaemia), but also to a direct effect of the beta 3-adrenergic agonist on the intestinal absorption processes.

Adrenergic beta-Agonists↗