Mechanisms underlying regional differences in lipolysis in human adipose tissue.

Wahrenberg, Hans; Lönnqvist, Fredrik; Arner, Peter

doi:10.1172/jci114187

Cited by 230 publications

(158 citation statements)

References 29 publications

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“…It is generally accepted that visceral adipose tissue is more insulin resistant than subcutaneous adipose tissue [47,48]. Consequently, portal NEFA drainage may be more important than the systemic flux in the development of liver steatosis.…”

Section: Discussionmentioning

confidence: 99%

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms

et al. 2005

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Aims/Hypothesis: Non-alcoholic fatty liver disease (NAFLD) has been associated with the metabolic syndrome. However, it is not clear whether insulin resistance is an independent feature of NAFLD, and it remains to be determined which of the in vivo actions of insulin are impaired in this condition. Methods: We performed a twostep (1.5 and 6 pmol min −1 kg −1 ) euglycaemic insulin clamp coupled with tracer infusion ([6,6-2 H 2 ]glucose and [ 2 H 5 ] glycerol) and indirect calorimetry in 12 non-obese, normolipidaemic, normotensive, non-diabetic patients with biopsy-proven NAFLD and six control subjects. Results: In NAFLD patients, endogenous glucose production (basal and during the clamp) was normal; however, peripheral glucose disposal was markedly decreased (by 30% and 45% at the low and high insulin doses, respectively, p<0.0001) at higher plasma insulin levels (p=0.05), due to impaired glucose oxidation (p=0.003) and glycogen synthesis (p<0.001). Compared with control subjects, glycerol appearance and lipid oxidation were significantly increased in NAFLD patients in the basal state, and were suppressed by insulin to a lesser extent (p<0.05-0.001). The lag phase of the in vitro copper-catalysed peroxidation of LDL particles was significantly shorter in the patients than in the control subjects (48±12 vs 63±13 min, p<0.04). Lipid oxidation was significantly related to endogenous glucose production, glucose disposal, the degree of hepatic steatosis, and LDL oxidisability. Conclusions/interpretation: Insulin resistance appears to be an intrinsic defect in NAFLD, with the metabolic pattern observed indicating that adipose tissue is an important site.

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Section: Discussionmentioning

confidence: 99%

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms

et al. 2005

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“…19 In human omental fat cells, the lipolytic activity is higher than in human subcutaneous fat cells, owing to the lower a 2 -adrenergic receptor ef®ciency and to site variations in the badrenoceptor subtypes. 20,21 In obese 22 or non-obese 23 subjects, the b-adrenergic lipolytic response is greater in subcutaneous abdominal than in gluteal adipocytes from both sexes. However, abdominal adipocytes of women showed lower a 2 -adrenergic antilipolytic sensitivity than did gluteal adipocytes, leading to a more pronounced regional difference in lipolysis in women than in men.…”

Section: Discussionmentioning

confidence: 99%

Impact of polymorphisms of the human β2-adrenoceptor gene on obesity in a French population

et al. 2000

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OBJECTIVE: To investigate the impact of two common polymorphisms in the human b b 2 -adrenoceptor gene (Gly16Arg and Gln27Glu substitutions) on obesity and anthropometric measurements as well as blood variables in a large sample of a French population. DESIGN AND SUBJECTS: Within the framework of the WHO-MONICA project, a population study composed of 1195 subjects aged 35 ± 64 y was randomly sampled from the electoral rolls of the Urban Community of Lille, in northern France. Subjects without any medical treatment (for hypercholesterolaemia, hypertension or diabetes mellitus) susceptible to interfere with body weight and biological variables were selected (n 836, 419 mena417 women, age 49.5 AE 8.1 y, body mass index (BMI) 25.7 AE 4.4 kgam 2 ). Subjects with a body mass index ! 30 kgam 2 were considered as obese (n 119, age 49.5 AE 8.2 y, BMI 33.9 AE 3.3 kgam 2 range 30 ± 44). MEASUREMENTS: Genotyping was carried out with allele-speci®c oligonucleotides hybridization. Association between genotypes and various obesity markers (body weight, body mass index, waist and waist-to-hip ratio), lipid, glucose and insulin variables were studied. RESULTS: The Gly16Arg and Gln27Glu polymorphisms were in complete linkage disequilibrium. Gln27Gln subjects had an increased risk of obesity (odds ratio (OR) 1.77, 95% CI 1.19 ± 2.62, P 0.005). This effect was mainly detected in men (OR 2.40, 95% CI 1.34 ± 4.27, P 0.003). Men bearing the Gln27Gln genotype had higher body weight, BMI, waist and hip circumferences and waist-to-hip ratio than others. Moreover, if Gln27Gln men carried in addition the Arg16 allele, the increase in body weight, BMI and waist-to-hip ratio was more important. CONCLUSION: Our results suggest that genetic variability of the b b 2 -adrenoceptor gene is implicated in body weight regulation and in the onset of obesity in French men.

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“…However, both states are characterized by increased FFA¯ux within the adipocyte and it has been suggested that UCP2 mRNA expression may be better correlated with fatty acid metabolism than with metabolic ef®-ciency. 34 Omental adipose tissue is known to have a higher rate of lipid turnover than subcutaneous adipose tissue, and this is related to a greater sensitivity to the lipolytic effects of catecholamines 35 and less sensitivity to the anti-lipolytic effects of insulin. 36,37 Thus, the greater UCP2 expression in human omental versus subcutaneous adipocytes would be consistent with a relationship between FFA¯ux and UCP2 expression.…”

Section: Discussionmentioning

confidence: 99%

Depot-related and thiazolidinedione-responsive expression of uncoupling protein 2 (UCP2) in human adipocytes

et al. 2000

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OBJECTIVES: Uncoupling protein 2 (UCP2) is a recently described homologue of the uncoupling protein of brown adipocytes (UCP1), which is expressed at high levels in human white adipose tissue. Studies were undertaken (1) to establish whether the expression of UCP2 mRNA varies in a depot-related manner in isolated human adipocytes, (2) to determine whether thiazolidinedione exposure in¯uences the expression of UCP2 mRNA in cultured human preadipocytes, and (3) to determine whether human UCP2 is targeted to mitochondria when transfected into mammalian cells. SUBJECTS: Abdominal subcutaneous and omental adipose tissue biopsies were obtained from adult patients undergoing elective intra-abdominal surgical procedures. MEASUREMENTS: A competitive reverse transcriptase-polymerase chain reaction (RT-PCR) was used to quantify UCP2 mRNA expression in human omental and subcutaneous adipocytes, and in cultured human preadipocytes differentiated in vitro using the thiazolidinedione, BRL49653. Chinese hamster ovary cells were transfected with a vector expressing human UCP2, and its cellular localization was determined by confocal immuno¯uorescence microscopy. RESULTS: Adipocytes isolated from human omentum consistently expressed more UCP2 mRNA than did subcutaneous adipocytes from the same subjects (mean fold difference 2.92 AE 0.44 P`0.001, n 11) with no effect of gender or body mass index being seen. BRL49653 treatment of subcutaneously, but not omentally, derived preadipocytes stimulated expression of UCP2 mRNA (5.1 AE 1.1 fold). Transfected human UCP2 was detected exclusively in mitochondria of CHO cells. CONCLUSIONS: Increased expression of UCP2 in human omental adipose tissue relative to subcutaneous adipose tissue is related to the expression levels in adipocytes per se, a ®nding which may relate to the particular functional attributes of this sub-population of adipocytes. Furthermore, BRL 49653 has site-speci®c effects of on the expression of UCP2 in human preadipocytes, a ®nding which may be relevant to the therapeutic effects of such compounds. Finally we present evidence for the mitochondrial localisation of human UCP2.

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Mechanisms underlying regional differences in lipolysis in human adipose tissue.

Cited by 230 publications

References 29 publications

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms

Insulin resistance in non-diabetic patients with non-alcoholic fatty liver disease: sites and mechanisms

Impact of polymorphisms of the human β2-adrenoceptor gene on obesity in a French population

Depot-related and thiazolidinedione-responsive expression of uncoupling protein 2 (UCP2) in human adipocytes

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