Circulating soluble leptin receptor, leptin, and insulin resistance before and after weight loss in obese children

Reinehr, Thomas; Kratzsch, Jürgen; Kieß, Wieland; Andler, Werner

doi:10.1038/sj.ijo.0803027

Cited by 84 publications

(72 citation statements)

References 35 publications

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“…PKC can induce A disintegrin and metalloprotease (ADAM) 17 (22), which is able to shed the extracellular domain of cytokine-like hormone receptors, such as the growth hormone-receptor and the OB-R, leading to increased levels of the soluble receptor. The fact that deficiency of substrates for the energy supply, such as lack of intracellular glucose in T1DM, leads to increased levels of circulating sOB-R is in agreement with previous data showing the same effect in conditions with weight loss, malnutrition, insulin treatment of T1DM with poor glycemic control, or nephrotic syndrome (14,(23)(24)(25)(26). Furthermore, our data suggest that age, height-SDS, and parameters of metabolic decompensation have the strongest power for the prediction of sOB-R variance.…”

Section: Discussionsupporting

confidence: 80%

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

Kratzsch

Knerr²,

Galler³

et al. 2006

eur j endocrinol

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Objective: Type 1 diabetes mellitus (T1DM) leads to increased serum levels of the soluble leptin receptor (sOB-R) by an as yet unknown cellular mechanism. The aim of our study was to investigate potential metabolic factors that may be associated with the induction of the sOB-R release from its membrane receptor. Materials and methods: Twenty-five children (aged between 1.5 and 17.0 years) were studied at the onset of T1DM. Blood samples were collected before (nZ25), during the first 18 h (meanGS.D. 11.1G 4.3 h, nZ16) and 92 h (47.5G22.5 h; nZ14) after beginning insulin therapy. Serum sOB-R and leptin levels were determined by in-house immunoassays. Results: The sOBR-level and the molar sOB-R/leptin ratio were significantly higher before than after starting insulin treatment (P!0.05). In contrast, leptin levels were significantly lower (P!0.05) before insulin therapy. The correlation between sOB-R and blood glucose (rZ0.49; P!0.05), as well as sOB-R with parameters of ketoacidosis, such as pH (rZK0.72), base excess (rZK0.70), and bicarbonate (rZK0.69) (P!0.0001) at diagnosis of T1DM remained significant during the first 18 h of insulin treatment. Multiple regression analysis revealed that base excess predicted 41.0% (P!0.001), age 16.4% (P!0.05), and height SDS 13.9% (P!0.01) of the sOB-R variance. Conclusions: Metabolic decompensation in children with new onset T1DM is associated with dramatic changes of the leptin axis; serum levels of sOB-R are elevated and of leptin are reduced. The molar excess of sOB-R over leptin (median 11.3) in this condition may contribute to leptin insensitivity. Upregulation of the soluble leptin receptor appears to be a basic mechanism to compensate for intracellular substrate deficiency and energy-deprivation state.European Journal of Endocrinology 155 609-614

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Section: Discussionsupporting

confidence: 80%

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

Kratzsch

Knerr²,

Galler³

et al. 2006

eur j endocrinol

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“…In contrast to the decrease of plasma clusterin, sObR increased markedly during weight reduction, confirming the results of earlier studies (26,27). There was no significant correlation between clusterin and sObR (r ϭ 0.21 before and 0.13 after weight reduction, respectively).…”

Section: Resultssupporting

confidence: 46%

Effect of Obesity on Plasma Clusterin: A Proposed Modulator of Leptin Action

et al. 2011

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Clusterin, a protein constituent of HDL, was recently shown to bind plasma leptin in vitro and has been proposed to modulate leptin activity. To gain insight into a possible role for plasma clusterin in human obesity, we measured plasma clusterin, leptin, soluble leptin receptor (sObR), and lipoproteins in 70 obese adolescents (12.4 Ϯ 1.6 y; BMI-SD score (SDS-BMI) 2.35 Ϯ 0.47) before and after 3 wk of weight reduction in a dietary camp and in 44 normal weight controls. Binding of plasma leptin to HDL or clusterin was studied using ultracentrifugation and immunoaffinity chromatography. During weight reduction, clusterin decreased from 14.6 Ϯ 4.1 to 10.3 Ϯ 2.9 mg/dL, p Ͻ 0.001) in obese adolescents, whereas sObR increased. However, baseline plasma clusterin in obese adolescents did not differ from controls. Clusterin did not correlate with SDS-BMI, weight loss, leptin, or lipoproteins. Only ϳ1% of plasma leptin was associated with clusterin/apoA-I complexes or with HDL. Our results do not support a role for plasma clusterin as an important leptin-binding protein or modulator of leptin action. The decrease of plasma clusterin during weight reduction may be an effect of the hypocaloric diet rather than being directly linked to weight loss. (Pediatr Res 69: 237-242, 2011)

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“…Expectedly, obese children had higher leptin levels compared with lean children. In contrast to this, the sOB-R serum levels were significantly lower in the obese children (33). There are, however, situations in which the molar excess of sOB-R over leptin is remarkably high.…”

Section: Predictors For the Metabolic Syndrome In Children-factors Frcontrasting

confidence: 43%

New Predictors of the Metabolic Syndrome in Children—Role of Adipocytokines

Körner¹,

et al. 2007

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ABSTRACT:There is ample discussion of the relevance of the metabolic syndrome, the definition criteria, and predictive power. Nevertheless, along with the increasing prevalence of childhood obesity, the prevalence of the metabolic syndrome in obese children is reported at 30%, irrespective of the definition applied. Because children are otherwise relatively free of co-morbidities, they constitute an interesting population in which to study the sequence of events of obesity-related pathology. The adipocytokines appear to be important in this respect. Leptin was initially suggested as a promising "antiobesity" hormone. New concepts indicate that, in humans, leptin and its soluble receptor may be more important in states of energy deficiency rather than a predictor of the metabolic syndrome. Adiponectin, on the other hand, is not only related to obesity and insulin resistance, but appears to be the strongest predictor for metabolic syndrome, even in children. In newborns and infants, both adipocytokines occur in high concentrations, even though this cannot completely explain the increased risk for ensuing metabolic disease later in life. Finally, low-grade systemic inflammation may underlie the clustering of metabolic risk factors, but their role in children remains to be specified. Overall factors from the adipose tissue may constitute not only markers but also mediators of metabolic sequelae of obesity. T he metabolic syndrome in children is not only a scientifically and clinically relevant issue but also a controversial and complex issue with many questions not satisfactorily answered, such as, "What is the metabolic syndrome?" "How is the situation in children?" "How can we predict it?" and "Does the adipose tissue contribute to it?" TERMS AND DEFINITION OF THE METABOLIC SYNDROMEThe term and concept of the metabolic syndrome was first introduced by Reaven in 1988 (1), when he noticed, from the analysis of experimental, clinical, and epidemiologic studies, the simultaneous occurrence of hyperinsulinemia with several other cardiovascular risk factors in the same patient and that this clustering results in a markedly higher cardiovascular morbidity. He already assumed that there might be one common underlying mechanism for those risk factors-insulin resistance. Certainly, obesity seems to be another strong predisposing factor for all those components. The concept of the metabolic syndrome was then defined and institutionalized and was widely applied in clinical medicine (2-4). However, recent re-evaluation lead to a critical appraisal of the term and questioned the concept of the metabolic syndrome. In a joint statement of the American Diabetes Association and the European Association of the Study of Diabetes, the clarity and accuracy of the existing definition was questioned (5). Some criteria used are ambiguous or incomplete, and it has not been proven that the predictive value of the "syndrome" over the predictive value of the single components themselves is actually higher. In addition, ongoing research has id...

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Circulating soluble leptin receptor, leptin, and insulin resistance before and after weight loss in obese children

Cited by 84 publications

References 35 publications

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

Metabolic decompensation in children with type 1 diabetes mellitus associated with increased serum levels of the soluble leptin receptor

Effect of Obesity on Plasma Clusterin: A Proposed Modulator of Leptin Action

New Predictors of the Metabolic Syndrome in Children—Role of Adipocytokines

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