In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity.

Bougnères, Pierre; Stunff, Catherine Le; Pecqueur, Claire; Pinglier, E; Adnot, P.; Ricquier, Daniel

doi:10.1172/jci119444

Cited by 116 publications

(88 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Consistent with our previous findings, the increase in BAT radiodensity during cold exposure suggests that intracellular TG utilization is the main fuel source for BAT oxidative metabolism and that plasma glucose and NEFA utilization rates by BAT are both trivial during acute cold exposure (5,6,34). Blunted lipolytic action of catecholamines in WAT is an early event in obesity in humans (40) and in BAT of obese Zucker rats (41) due to a reduction in b-adrenergic receptor density. Reduced b-adrenergic receptor density was also demonstrated in BAT of high fat-, high sucrose-fed mice (32).…”

supporting

confidence: 88%

Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

et al. 2015

View full text Add to dashboard Cite

Spontaneous glucose uptake by brown adipose tissue (BAT) is lower in overweight or obese individuals and in diabetes. However, BAT metabolism has not been previously investigated in patients with type 2 diabetes during controlled cold exposure. Using positron emission tomography with , a fatty acid tracer, BAT oxidative metabolism and perfusion and glucose and nonesterified fatty acid (NEFA) turnover were determined in men with well-controlled type 2 diabetes and age-matched control subjects under experimental cold exposure designed to minimize shivering. Despite smaller volumes of 18 FDG-positive BAT and lower glucose uptake per volume of BAT compared with young healthy control subjects, cold-induced oxidative metabolism and NEFA uptake per BAT volume and an increase in total body energy expenditure did not differ in patients with type 2 diabetes or their age-matched control subjects. The reduction in 18 FDG-positive BAT volume and BAT glucose clearance were associated with a reduction in BAT radiodensity and perfusion. 18 FDG-positive BAT volume and the cold-induced increase in BAT radiodensity were associated with an increase in systemic NEFA turnover. These results show that cold-induced NEFA uptake and oxidative metabolism are not defective in type 2 diabetes despite reduced glucose uptake per BAT volume and BAT "whitening."

show abstract

supporting

confidence: 88%

Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

et al. 2015

View full text Add to dashboard Cite

show abstract

“…Also, in vivo lipolysis is influenced by endocrine, paracrine, and autocrine factors, which modify the lipolytic response to catecholamines (35,36) underlining the importance of in vivo studies. The idea that receptor and postreceptor defects on isolated fat cells could be relevant for the pathogenesis of obesity was suggested in a recent in vivo study on obese children using epinephrine infusion (37). The present study using in situ stimulation of a cutaneous nerve and measurement of glycerol release within its innervation territory may support the concept of a reduction of adrenergically mediated lipolysis in obesity.…”

Section: Discussionsupporting

confidence: 71%

The subcutaneous lipolytic response to regional neural stimulation is reduced in obese women.

et al. 2000

View full text Add to dashboard Cite

Disturbed fat tissue metabolism with a reduction of the lipolytic rate could be an important pathogenetic factor in obesity. Lipolysis of the subcutaneous tissue of the thigh is partly under neural control and can be increased by intraneural stimulation of the lateral cutaneous femoral nerve in lean women. In the present study, we tested whether the lipolytic response to intraneural stimulation is altered in vivo in obese subjects. Seven obese women were examined and the results were compared with those of seven age-matched lean women. After an overnight fast, the lateral cutaneous femoral nerve was intraneurally stimulated for 10 min, and the local subcutaneous lipolytic response to this procedure was evaluated with microdialytic measurements of interstitial glycerol concentrations in the receptive field of the stimulated nerve fascicle. To exclude unspecific effects of stimulation, lipolysis was also controlled in a corresponding area of the contralateral leg. Intraneural stimulation produced no significant change in subcutaneous lipolysis in obese women (25.7 ± 9.7%, NS). This finding is in sharp contrast with the marked regional lipolytic response in lean women in which the same stimulation procedure enhanced the regional interstitial glycerol levels by 72 ± 17% (P < 0.05) compared with the unstimulated corresponding area of the contralateral leg. These in vivo results suggest that human obesity is characterized by a profound unresponsiveness of the subcutaneous adipose tissue to neurally stimulated lipolysis. This could be an important factor in the development and treatment of obesity. Diabetes 49:1875-1879, 2000 T he pathogenesis of obesity has been suggested to be intimately linked to the catecholaminergic regulation of lipolysis and the function of the sympathetic nervous system (1-3). Norepinephrine and epinephrine activate lipolysis via ␤ 1 -, ␤ 2 -, and ␤ 3 -adrenoceptors and inhibit it via ␣ 2 -adrenoceptors, and these neurotransmitters are the most important lipolytic substances in vivo (4). Defects of catecholamine-induced lipolysis have been observed in a number of obese subjects, and polymorphisms of the ␤ 2 -(5) and ␤ 3 -receptors (6) were suggested as explanations for this observation.The importance of sympathetic innervation of fat tissue is underlined by the observation that the recently described weight-regulating hormones, leptin (7), and the proopiomelanocorticotropin-derivate ␣-MSH (8) not only reduce appetite but also induce sympathoexcitation via the central nervous system. The relevance of such effects is obvious for the metabolically highly active brown adipose tissue in rats, which is densely innervated by sympathetic nerves directly controlled by autonomic brain stem centers (9-11). By comparison, the innervation of white adipose tissue (WAT) is sparse (12), and its role in regulating fat tissue metabolism is ill defined in humans (9,13). Recent studies from our laboratory on subjects with spinal cord injuries suggested that the neural control of basal WAT lipolysis appears to be i...

show abstract

“…As expected, plasma levels of insulin in our lean adolescent girls were elevated to the same degree as in the obese women, yet obese women were significantly resistant to ␤ 2 -adrenergic stimulation compared with the lean adolescents. Similarly, even if insulin is infused in lean children to match hyperinsulinemia in the obese, the lean children are more responsive to catecholamine stimulation than obese children (9). It is conceivable that the downregulation of ␤ 2 -adrenoceptors is secondary to a chronic stimulation of sympathetic activity by the hyperinsulinemia seen in obesity.…”

Section: Discussionmentioning

confidence: 99%

“…Because catecholamines are the only hormones with pronounced lipolytic action in humans (6), the effect of obesity in adults on the responsiveness to catecholamines has been extensively studied. Both in vitro and in vivo studies have demonstrated that subcutaneous abdominal adipose tissue in obese adults is resistant to the lipolytic effects of catecholamines (7)(8)(9). Moreover, even though subcutaneous adipose tissue contains ␤ 1 -, ␤ 2 -, and ␤ 3 -adrenoceptors, obesityinduced catecholamine resistance appears primarily because of defects in ␤ 2 -stimulation (7), with impaired ␤ 1 -stimulation having a secondary role.…”

Section: Impaired In Vivo Stimulation Of Lipolysis In Adiposementioning

confidence: 99%

Impaired in vivo stimulation of lipolysis in adipose tissue by selective beta2-adrenergic agonist in obese adolescent girls.

et al. 2000

View full text Add to dashboard Cite

Studies performed in adults with long-standing obesity suggest a reduced lipolytic sensitivity to catecholamines in subcutaneous abdominal adipose tissue (AT). We used microdialysis to study the in situ lipolytic effects of dobutamine (selective ␤ 1 -agonist) and terbutaline (selective ␤ 2 -agonist) on glycerol release (lipolytic index) in abdominal subcutaneous AT in 10 obese girls aged 13-17 years, BMI 38 ± 2.1 kg/m 2 , and in 7 lean girls aged 11-17 years, BMI 21 ± 1.1 kg/m 2 , and compared them with 10 obese women aged 21-39 years, BMI 36 ± 1.6 kg/m 2 , and 10 lean women aged 18-42 years, BMI 21 ± 0.4 kg/m 2 . Terbutaline at 10 -6 mol/l stimulated glycerol release more efficiently in lean girls than in obese girls (peak response ~350 vs. 150% of control, P < 0.01). At the lower concentration of agonist, no significant difference was seen. In women, terbutaline was more effective in lean than in obese women in stimulating glycerol release at both 10 -8 mol/l (peak response lean ~175% vs. obese 125% of control) and 10 -6 mol/l (~300 vs. 150% of control, P < 0.05). No significant difference in glycerol release between obese and lean girls or women was detected with selective ␤ 1 -stimulation. Our data demonstrate a specific impairment in the capacity of ␤ 2 -adrenergic agonists to promote lipolysis in subcutaneous abdominal adipose tissue of obese adolescent girls and women. Thus, decreased mobilization of fat during activation of the adrenergic system might be present early in the development of adolescent obesity. Diabetes 49:2149-2153, 2000 T he prevalence of obesity in children as well as in adults is steadily increasing in the U.S. (1). The early-onset type of obesity deserves special attention because youth-onset obesity is often the precursor of the most intractable form of adult obesity (2). Furthermore, the comorbid conditions that accompany obesity in adults, such as type 2 diabetes, dyslipidemia, and hypertension, are seen with increasing frequency in overweight adolescents and even preadolescents (3,4).Although the pathogenesis of obesity is poorly understood, it is believed to result from a complex interaction between genetic and environmental factors (5), leading to a more efficient accumulation of fat and to an impaired ability to mobilize fat. Because catecholamines are the only hormones with pronounced lipolytic action in humans (6), the effect of obesity in adults on the responsiveness to catecholamines has been extensively studied. Both in vitro and in vivo studies have demonstrated that subcutaneous abdominal adipose tissue in obese adults is resistant to the lipolytic effects of catecholamines (7-9). Moreover, even though subcutaneous adipose tissue contains ␤ 1 -, ␤ 2 -, and ␤ 3 -adrenoceptors, obesityinduced catecholamine resistance appears primarily because of defects in ␤ 2 -stimulation (7), with impaired ␤ 1 -stimulation having a secondary role. Whereas obese children have been shown to have a reduced lipolytic response to systemic epinephrine infusion (9), the effect of juvenile obesi...

show abstract

In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity.

Cited by 116 publications

References 43 publications

Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

The subcutaneous lipolytic response to regional neural stimulation is reduced in obese women.

Impaired in vivo stimulation of lipolysis in adipose tissue by selective beta2-adrenergic agonist in obese adolescent girls.

Contact Info

Product

Resources

About