Change in β1-adrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss

2005 ◽  
Vol 108 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Mads RASMUSSEN ◽  
Anita BELZA ◽  
Thomas ALMDAL ◽  
Søren TOUBRO ◽  
Palle BRATHOLM ◽  
...  

The aim of the present study was to examine gene expression and protein concentrations of β1- and β2-adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. β-Adrenergic receptor mRNA levels were quantified by reverse transcription-PCR–HPLC. β-Adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8±0.8 kg (mean±S.E.M.) during diet treatment. There was a 34% decrease in the β1-adrenergic receptor mRNA level (0.92±0.09 compared with 0.61±0.06 amol/μg of DNA; P<0.002). β2-Adrenergic receptor mRNA did not decrease significantly. β2-Adrenergic receptor protein concentration decreased 37% (25.5±7.1 compared with 16.0±5.6 arbitrary units/ng of DNA; P=0.008), whereas β1-adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of β1-adrenergic receptor protein (r=0.65, P<0.003) and changes in receptor protein concentration (r=0.50, P=0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between β1-adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation.

2003 ◽  
Vol 104 (2) ◽  
pp. 93-102 ◽  
Author(s):  
Mads RASMUSSEN ◽  
Thomas ALMDAL ◽  
Palle BRATHOLM ◽  
Niels Juel CHRISTENSEN

The aim of the present study was to quantify β2-adrenoceptor protein content in adipose tissue during fasting, and to study the relationships between β2-adrenoceptor protein and mRNA levels and changes in metabolites related to lipolysis. Groups of male subjects with a body mass index of <25kg/m2 or >30kg/m2 fasted for 60h. Abdominal subcutaneous fat biopsies were analysed for receptor mRNA levels by reverse transcription–PCR–HPLC. The β2-adrenoceptor protein concentration was measured by Western blotting using fluorescence laser scanning for detection. The β2-adrenoceptor protein concentration per cell (on a DNA basis) was higher in obese subjects (P<0.03). There were highly significant relationships between β2-adrenoceptor protein concentration and both body mass index and waist/hip ratio (P<0.001 for both). Furthermore, there was an inverse relationship between the receptor protein concentration and the serum β-hydroxybutyrate level during fasting (P<0.005). β2-Adrenoceptor protein levels decreased in both groups during fasting, to a similar degree. Basal β2-adrenoceptor mRNA levels were similar in the two groups, but there was a smaller increase in the obese group during fasting (P<0.03). The increased β2-adrenoceptor protein level in obese subjects is likely to be related to the greater plasma membrane area of their adipocytes. The decrease during fasting may be due to increased binding of noradrenaline and subsequent internalization and degradation of the receptor. Elevated levels of less responsive β2-adrenoceptor protein in obese subjects may contribute to the development of obesity.


1997 ◽  
Vol 322 (1) ◽  
pp. 145-150 ◽  
Author(s):  
John N. FAIN ◽  
Elizabeth C. CORONEL ◽  
Michael J. BEAUCHAMP ◽  
Suleiman W. BAHOUTH

The level of leptin [the obese (ob) gene product] mRNA is markedly elevated in hypothyroid male rats. The administration of tri-iodothyronine (T3) to hypothyroid rats resulted in a 40% decrease in leptin mRNA at 8 h. This decrease in leptin mRNA was associated with a parallel decline in circulating leptin levels of about 50% at 24 h. Conversely, β3-adrenergic receptor mRNA levels were markedly decreased in epididymal adipose tissue from hypothyroid rats. T3 administration resulted in a 147% increase at 12 h in β3-adrenergic receptor mRNA. There was a corresponding increase due to T3 in the lipolytic response to the specific β3-adrenergic agonist CL 316,243 that paralleled the increase in β3-adrenergic receptor mRNA. T3-mediated changes in leptin and β3-adrenergic receptor mRNAs were blocked by cycloheximide, suggesting the involvement of short-lived proteins in these effects. The present results indicate that T3 has opposite effects to those of insulin on the white adipose tissue of rats with respect to leptin mRNA expression.


Author(s):  
Per-arne Svensson ◽  
Britt Gabrielsson ◽  
Margareta Jernås ◽  
Anders Gummesson ◽  
Kajsa Sjöholm

AbstractAldoketoreductase 1C3 (AKR1C3) is a functional prostaglandin F synthase and a negative modulator of the availability of ligands for the nuclear receptor peroxisome proliferator-activated receptor-gamma (PPARγ). AKR1C3 expression is known to be associated with adiposity, one of the components of the metabolic syndrome. The aim of this study was to characterize the expression of AKR1C3 in the adipose tissue and adipocytes and to investigate its potential role in the metabolic syndrome. Using microarray analysis and realtime PCR, we studied the expression of AKR1C3 in adipose tissue samples from obese subjects with or without metabolic complications, during very low calorie diet-induced weight loss, and its expression in isolated human adipocytes of different sizes. The adipose tissue AKR1C3 expression levels were marginally lower in obese subjects with the metabolic syndrome compared with the levels in healthy obese subjects when analyzed using microarray (p = 0.078) and realtime PCR (p < 0.05), suggesting a secondary or compensatory effect. The adipose tissue mRNA levels of AKR1C3 were reduced during and after dietinduced weight-loss compared to the levels before the start of the diet (p < 0.001 at all time-points). The gene expression of AKR1C3 correlated with both adipose tissue mRNA levels and serum levels of leptin before the start of the diet (p < 0.05 and p < 0.01, respectively). Furthermore, large adipocytes displayed a higher expression of AKR1C3 than small adipocytes (1.5-fold, p < 0.01). In conclusion, adipose tissue AKR1C3 expression may be affected by metabolic disease, and its levels are significantly reduced in response to dietinduced weight loss and correlate with leptin levels.


2006 ◽  
Vol 155 (1) ◽  
pp. 161-165 ◽  
Author(s):  
M J Kim ◽  
M Maachi ◽  
C Debard ◽  
E Loizon ◽  
K Clément ◽  
...  

Objective: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)γ2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss. Methods: Twenty-three non-diabetic obese subjects with normal (NGT, n=11) or impaired glucose tolerance (IGT, n=12) (age, 47±3 years; body mass index, 39.3±1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue. Results: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P=0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARγ2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARγ2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin. Conclusion: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.


2006 ◽  
Vol 291 (4) ◽  
pp. E843-E848 ◽  
Author(s):  
Lauren N. Bell ◽  
Jennifer L. Ward ◽  
Mikako Degawa-Yamauchi ◽  
Jason E. Bovenkerk ◽  
RoseMarie Jones ◽  
...  

Serum HGF is elevated in obese individuals. This study examined the contribution of excess adipose tissue to increased circulating HGF levels in obesity. Serum HGF was measured by ELISA before and after weight loss due to bariatric surgery or a 24-h fast. At 6.1 ± 0.1 mo following surgery, BMI (50.6 ± 1.6 vs. 35.1 ± 1.3 kg/m2; P < 0.0001) and serum HGF were significantly decreased (1,164 ± 116 vs. 529 ± 39 pg/ml, P < 0.001). A 24-h fast did not change serum HGF, but serum leptin was significantly reduced (67.7 ± 7.1 vs. 50.3 ± 8.3 ng/ml, P = 0.02). HGF secretion in vitro from adipocytes of obese (BMI 40.3 ± 2.8 kg/m2) subjects was significantly greater (80.9 ± 10.4 vs. 21.5 ± 4.0 pg/105 cells, P = 0.008) than release from adipocytes of lean (BMI 23.3 ± 1.4 kg/m2) subjects. HGF mRNA levels determined by real-time RT-PCR were not different in adipocytes from lean (BMI 24.0 ± 0.8 kg/m2) and obese (45.7 ± 3.0 kg/m2) subjects, but serum HGF was significantly elevated in the obese individuals studied (787 ± 61 vs. 489 ± 49 pg/ml, P = 0.001). TNF-α (24 h treatment) significantly increased HGF release from subcutaneous adipocytes 23.6 ± 8.3% over control ( P = 0.02). These data suggest that elevated serum HGF in obesity is in part attributable to excess adipose tissue and that this effect can be reversed by reducing adipose tissue mass through weight loss. Increased HGF secretion from adipocytes of obese subjects may be due to posttranscriptional events possibly related to adipocyte size and stimulation by elevated TNF-α in the adipose tissue of obese individuals.


1991 ◽  
Vol 277 (3) ◽  
pp. 625-629 ◽  
Author(s):  
J P Revelli ◽  
R Pescini ◽  
P Muzzin ◽  
J Seydoux ◽  
M G Fitzgerald ◽  
...  

The aim of the present work was to study the effect of hypothyroidism on the expression of the beta-adrenergic receptor (beta-AR) in interscapular brown adipose tissue and heart. The total density of plasma membrane beta-AR per tissue is decreased by 44% in hypothyroid rat interscapular brown adipose tissue and by 55% in hypothyroid rat heart compared with euthyroid controls. The effects of hypothyroidism on the density of both beta 1- and beta 2-AR subtypes were also determined in competition displacement experiments. The densities of beta 1- and beta 2-AR per tissue are decreased by 50% and 48% respectively in interscapular brown adipose tissue and by 52% and 54% in the heart. Northern blot analysis of poly(A)+ RNA from hypothyroid rat interscapular brown adipose tissue demonstrated that the levels of beta 1- and beta 2-AR mRNA per tissue are decreased by 73% and 58% respectively, whereas in hypothyroid heart, only the beta 1-AR mRNA is decreased, by 43%. The effect of hypothyroidism on the beta 1-AR mRNA is significantly more marked in the interscapular brown adipose tissue than in the heart. These results indicate that beta-AR mRNA levels are differentially regulated in rat interscapular brown adipose tissue and heart, and suggest that the decrease in beta-AR number in interscapular brown adipose tissue and heart of hypothyroid animals may in part be explained by a decreased steady-state level of beta-AR mRNA.


1997 ◽  
Vol 82 (6) ◽  
pp. 1926-1931 ◽  
Author(s):  
Nobuharu Fujii ◽  
Takeshi Shibata ◽  
Sachiko Homma ◽  
Haruo Ikegami ◽  
Kazuo Murakami ◽  
...  

Fujii, Nobuharu, Takeshi Shibata, Sachiko Homma, Haruo Ikegami, Kazuo Murakami, and Hitoshi Miyazaki. Exercise-induced changes in β-adrenergic-receptor mRNA level measured by competitive RT-PCR. J. Appl. Physiol. 82(6): 1926–1931, 1997.—Competitive reverse transcription-polymerase chain reaction (RT-PCR) analysis was used to clarify whether dynamic exercise-induced increases in β-adrenergic-receptor (β-AR) number in human lymphocytes are accompanied by increases in the β-AR mRNA level. Sixteen healthy subjects performed cycle ergometry until exhaustion. Before and immediately after exercise, peripheral blood was drawn from a forearm vein for preparation of lymphocytes. Both the β-AR mRNA level and the β-AR number were significantly increased by exercise. The changes in β-AR mRNA level and β-AR number were significantly correlated ( r = 0.63, P < 0.01). This finding suggests that a rapid increase in β-AR mRNA level might be an early adaptive response of the sympathetic nervous system to dynamic exercise. In vitro incubation of lymphocytes with epinephrine had no effect on β-AR mRNA levels, nor did adenosine 3′,5′-cyclic monophosphate, protein kinase C, or intracellular Ca2+ increase the β-AR mRNA level in vitro. Therefore, it appears that other mechanisms underlie the exercise-induced elevation of β-AR mRNA levels in human lymphocytes.


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