1- and  2-Adrenoceptor-Mediated Thermogenesis and Lipid Utilization in Obese and Lean Men

Abstract

The aim of this study was to elucidate the roles of the ␤ 1 -and the ␤ 2 -adrenoceptors in thermogenesis and lipid utilization in obesity. The ␤ 1 -adrenoceptor study was performed in 9 obese and 10 lean men and consisted of 4 30-min periods during which subjects received consecutive infusions of 0, 3, 6, and 9 g/kg fat-free mass (FFM)⅐min dobutamine. Energy expenditure, lipid oxidation, and plasma nonesterified fatty acids and glycerol concentrations increased similarly in both groups during ␤ 1 -adrenergic stimulation. The ␤ 2 -adrenoceptor study was performed in 10 obese and 11 lean men and involved 3 45-min periods during which 0, 50, and 100 ng/kg FFM⅐min salbutamol were given in combination 1.2 g/kg FFM⅐min atenolol (bolus, 50 g/kg FFM). During ␤ 2 -adrenergic stimulation, the increases in energy expenditure and plasma nonesterified fatty acids and glycerol concentrations were reduced in the obese group. Furthermore, lipid oxidation significantly increased in the normal weight group, but remained similar in the overweight group. In conclusion, these data suggest that ␤ 1 -adrenoceptor-mediated metabolic processes are similar in both groups, but ␤ 2 -adrenoceptor-mediated increases in thermogenesis and lipid utilization are impaired in the obese. (J Clin Endocrinol Metab 86: [2191][2192][2193][2194][2195][2196][2197][2198][2199] 2001) T HE SYMPATHETIC nervous system plays an important role in the regulation of thermogenesis and lipid utilization. Studies in which the endogenous catecholamines norepinephrine (1, 2) and epinephrine (3-5) (both nonselective ␣-and ␤-adrenoceptor agonists) are infused show significant increases in energy expenditure, lipid oxidation, and lipolysis. The roles of the individual adrenoceptor subtypes in thermogenesis have also been studied. ␣-Adrenergic stimulation does not affect whole body thermogenesis (3, 6), whereas nonselective ␤-adrenergic stimulation with isoprenaline significantly increases energy expenditure and lipid utilization (7). During only ␤ 1 -adrenergic stimulation with dobutamine (8, 9) or only ␤ 2 -adrenergic stimulation with salbutamol (6) or terbutaline (10), energy expenditure, lipid oxidation, and lipolysis increase as well. In rats, ␤ 3 -adrenergic stimulation leads to significant increases in energy expenditure and lipid utilization (11,12). However, the rat ␤ 3 -adrenoceptor differs pharmacologically from the human ␤ 3 -adrenoceptor (13, 14), and consequently, the specific ␤ 3 -adrenoceptor agonists used in rats are only weak agonists in humans. Until now, no highly selective ␤ 3 -adrenoceptor agonist or antagonist has been available for administration in humans.Obese subjects may show an impaired response of thermogenesis during norepinephrine infusion (15, 16), but responses similar to those in lean subjects are also frequently found during norepinephrine (17, 18), epinephrine (5, 19), and isoprenaline (7) infusion. Others only found an impaired thermogenic response when very obese men were compared with very lean men (20) or only during ove...

Lipolytic and nutritive blood flow response to β-adrenoceptor stimulation in situ in subcutaneous abdominal adipose tissue in obese men

“…In summary, nonselective b-, b 1 -and b 2 -adrenoceptormediated increases in interstitial glycerol concentration and local nutritive blood flow were similar in subcutaneous abdominal adipose tissue in obese and lean men. This suggests that the diminished whole-body b-adrenoceptormediated lipolytic response, as reported earlier by our group, 3,5 is probably not for a large part explained by a blunted local adipocyte b-adrenergic sensitivity or nutritive blood flow. More likely, the impaired whole-body lipolytic response during i.v.…”

“…4 In an earlier study, we showed that this blunted b-adrenoceptor-mediated lipolytic response only occurs during selective b 2 -adrenergic stimulation, whereas b 1 -adrenoceptor-mediated increases in lipolysis are similar in obese and lean men. 5 Several mechanisms may be responsible for the impaired whole-body b-adrenoceptor-mediated lipolytic response. On the one side, adipocyte b-adrenergic sensitivity for lipolysis might be diminished.…”

Influence of adiposity on tonic sympathetic support of resting metabolism in healthy adults

“…We should emphasize that there is evidence that the increase in metabolic rate in response to b-AR stimulation is smaller with increasing adiposity, 25,26 as may be the increase in fat oxidation, 25,27 heart rate, 8,25 and blood flow to adipose tissue. 7 Chronically elevated sympathetic activity with increasing total 12,28,29 and abdominal 4,30 adiposity may reduce b-AR responsiveness due to desensitization of the b-AR signaling pathway [9][10][11] and explain these previous observations.…”

Gln27Glu polymorphism in the beta2 adrenergic receptor gene and lipid metabolism during exercise in obese women

“…When ANOVA for group was significant, unpaired Student's t-test was performed. 4 The SPSS 7.5 version for WINDOWS was used for the statistical analysis.…”

“…2,3 Furthermore, it has been suggested that ADRB2 is responsible for the impaired effects in thermogenesis, lipid oxidation and lipolysis in the obese in vivo. 4 Several polymorphisms have been described 5 both in the coding region of the ADRB2 gene (Arg16Gly, Gln27Gln, Thr164Ile) and in the 5 0 leader cistron (Cys19Arg), that result in significantly changed functions of this receptor. 6 -8 Indeed, polymorphisms in the coding region showed an ADRB2 functional impairment in recombinant cells.…”