Inhibition of Cortisol Biosynthesis Decreases Circulating Leptin Levels in Obese Humans

Dagogo‐Jack, Samuel; Tykodi, Gunjan; Umamaheswaran, Indira

doi:10.1210/jc.2005-0803

Cited by 26 publications

(18 citation statements)

References 19 publications

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“…It has been shown that short-term administration of glucocorticoids increases leptin secretion (36)(37)(38)(39), whereas long-term intrinsic glucocorticoid excess such as in patients with Cushing's syndrome has no effect on leptin levels (40). DagogoJack et al demonstrated that a metyrapone-induced inhibition of cortisol biosynthesis results in hypoleptinemia (41). In our cohort, we did not find any association of the leptin axis with equivalent HC dosage or the used glucocorticoid.…”

Section: Discussioncontrasting

confidence: 57%

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

Völkl¹,

Simm²,

Körner³

et al. 2009

European Journal of Endocrinology

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Objective: Congenital adrenal hyperplasia (CAH) patients are at a higher risk to develop obesity. The role of leptin in CAH is still controversial. Our study aimed to evaluate serum levels of leptin, the soluble leptin receptor (sOB-R), and the sOB-R: leptin molar ratios in a cohort of CAH children and adolescents, and their associations with clinical and metabolic parameters. Methods: We studied 51 CAH patients, aged 5.6-19.6 years (median 11.8, nZ30 females) crosssectionally. All patients had genetically proven CAH and received standard steroid substitution therapy. Blood specimens were taken after overnight fasting between 0800 and 1000 h. For the analyses of leptin and sOB-R, matched pairs were built with healthy Caucasian patients for sex, Tanner stage (TS), chronologic age (CA), and body mass index (BMI). Results: BMI and SDS were significantly elevated compared with the reference population. Leptin levels were not different between matched pairs, whereas sOB-R levels were significantly lower in CAH. Consequently, the sOB-R: leptin molar ratios were significantly decreased in CAH. Correlation analyses in CAH patients revealed significant relationship between leptin and CA, TS, BMI, and homeostasis model assessment of insulin resistance. Similar results were obtained for the matched control group. For sOB-R, we found no significant correlation for CA, TS, or BMI in CAH, but we did in the controls. There were significant correlations for androgens within the CAH group. Additional analyses revealed no correlation with steroid medication or metabolic control. Conclusions: Our data show that an altered leptin axis with normal serum leptin concentrations but decreased sOB-R serum levels may contribute to the increased risk of overweight and obesity in CAH.

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Section: Discussioncontrasting

confidence: 57%

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

Völkl¹,

Simm²,

Körner³

et al. 2009

European Journal of Endocrinology

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“…Leptin has been shown to have pleiotropic effects in regulating appetite, fat metabolism, growth, reproduction, body temperature, bone remodeling, immune function, stress, inflammatory responsiveness, hematopoiesis and angiogenesis (Steppan et al 2000;Dagogo-Jack et al 2005;Swoap 2008;Friedman 2009;Lafrance et al 2010;Copeland et al 2011). Notably, because of the tremendous differences in gene sequence, studies of leptin in fish lag behind studies in mammals significantly (Copeland et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Effects of glucose, insulin and triiodothyroxine on leptin and leptin receptor expression and the effects of leptin on activities of enzymes related to glucose metabolism in grass carp (Ctenopharyngodon idella) hepatocytes

Zhou

Yuan

et al. 2015

Fish Physiol Biochem

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Leptin is an important regulator of appetite and energy expenditure in mammals, but its role in fish metabolism control is poorly understood. Our previous studies demonstrated that leptin has an effect on the regulation of food intake and energy expenditure as well as lipid metabolism (stimulation of lipolysis and inhibition of adipogenesis) in the grass carp Ctenopharyngodon idella. To further investigate the role of leptin in fish, the effects of glucose, insulin and triiodothyroxine (T3) on the expression levels of leptin and leptin receptor (Lepr) and the effects of leptin on the activities of critical glucose metabolism enzymes in grass carp hepatocytes were evaluated in the present study. Our data indicated that leptin gene expression was induced by glucose in a dose-dependent manner, while Lepr gene expression exhibited a biphasic change. A high dose of insulin (100 ng/mL) significantly up-regulated the expression of leptin and Lepr. Leptin expression was markedly up-regulated by a low concentration of T3 but inhibited by a high concentration of T3. T3 up-regulated Lepr expression in a dose-dependent manner. Together, these data suggest that leptin had a close relationship with three factors (glucose, insulin and T3) and might participate in the regulation of glucose metabolism in grass carp. In addition, we also found that leptin affected the activities of key enzymes that are involved in glucose metabolism, which might be mediated by insulin receptor substrate-phosphoinositol 3-kinase signaling.

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“…They are chronically obese, hyperphagic, hypothermic, and do not sexually mature; injections of leptin rescues all of these phenotypes. Leptin has demonstrated effects in regulating appetite, fat metabolism, reproduction, body temperature, growth, bone remodeling, immune function, stress, inflammatory responsiveness, hematopoiesis, and angiogenesis (Pelleymounter et al, 1995; Barash et al, 1996; Bennett et al, 1996; Grunfeld et al, 1996; Fruhbeck et al, 1997; Sierra-Honigmann et al, 1998; Steppan et al, 2000; Dagogo-Jack et al, 2005; Lafrance et al, 2010; and reviewed in Swoap, 2008; Friedman, 2009). Its pleiotropic effects and its potential for treating obesity have resulted in >28,000 published studies to date (ISI).…”

Section: Leptin As An Integrating Signal In Mammalsmentioning

confidence: 99%

Leptin in Teleost Fishes: An Argument for Comparative Study

Copeland¹,

Duff²,

Liu³

et al. 2011

Front. Physio.

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All organisms face tradeoffs with regard to how limited energy resources should be invested. When is it most favorable to grow, to reproduce, how much lipid should be allocated to storage in preparation for a period of limited resources (e.g., winter), instead of being used for growth or maturation? These are a few of the high consequence fitness “decisions” that represent the balance between energy acquisition and allocation. Indeed, for animals to make favorable decisions about when to grow, eat, or reproduce, they must integrate signals among the systems responsible for energy acquisition, storage, and demand. We make the argument that leptin signaling is a likely candidate for an integrating system. Great progress has been made understanding the leptin system in mammals, however our understanding in fishes has been hampered by difficulty in cloning fish orthologs of mammalian proteins and (we assert), underutilization of the comparative approach.

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Inhibition of Cortisol Biosynthesis Decreases Circulating Leptin Levels in Obese Humans

Abstract: We conclude that metyrapone-induced inhibition of cortisol biosynthesis results in hypoleptinemia, which indicates that glucocorticoids may play an important role in the physiological regulation of leptin.

Cited by 26 publications

References 19 publications

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

Does an altered leptin axis play a role in obesity among children and adolescents with classical congenital adrenal hyperplasia due to 21-hydroxylase deficiency?

Effects of glucose, insulin and triiodothyroxine on leptin and leptin receptor expression and the effects of leptin on activities of enzymes related to glucose metabolism in grass carp (Ctenopharyngodon idella) hepatocytes

Leptin in Teleost Fishes: An Argument for Comparative Study

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