Leptin treatment of patients with anorexia nervosa? The urgent need for initiation of clinical studies

Albayrak, Özgür

doi:10.1007/s00787-012-0243-3

Cited by 25 publications

(19 citation statements)

References 25 publications

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“…To our knowledge, there is only one study that empirically investigated changes in leptin and depressive symptoms concomitantly. In contrast to the proposal of Hebebrand et al [24], Rybakowski et al [22] observed an inverse relationship of the rise in leptin and the amelioration of depressive symptoms in a longitudinal study in AN patients during weight recovery. However, in this study mood and leptin were assessed only twice–once at admission and again at discharge.…”

Section: Introductioncontrasting

confidence: 63%

“…Recently, a strong claim for the initiation of clinical trials of leptin treatment in AN patients has been made [24]. Our results add a caveat to this suggestion; even if leptin may be a helpful pharmaceutical in less severely ill AN patients—and possibly also alleviate depressed mood in these patients—leptin administration could have detrimental effects on mood and anxiety in those AN patients who are severely ill and emaciated.…”

Section: Discussionmentioning

confidence: 77%

“…In the context of AN, the relationship of leptin and depressive symptoms has rarely been investigated. Based on the clinical observation that during refeeding body weight (and thus leptin) increases while simultaneously mood ameliorates Hebebrand et al [24] hypothesized that leptin may mediate mood improvements in AN patients. To our knowledge, there is only one study that empirically investigated changes in leptin and depressive symptoms concomitantly.…”

Section: Introductionmentioning

confidence: 99%

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Time Course of Leptin in Patients with Anorexia Nervosa during Inpatient Treatment: Longitudinal Relationships to BMI and Psychological Factors

Stroe-Kunold¹,

Buckert²,

Friederich³

et al. 2016

PLoS ONE

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BackgroundLeptin, a hormone secreted by adipose tissue, appears to play a major role in the homeostasis of body weight and psychobiological processes associated with anorexia nervosa (AN). However, there is scarce data on its exact influence on this disorder, in particular data over time.ObjectiveThe present study addresses whether leptin changes during inpatient treatment play a role for treatment outcome and psychological factors in underweight AN patients.MethodsIn order to understand whether leptin’s role differs in relation to AN severity, data were assessed from 11 patients with a very low BMI and a higher chronicity (high severity group; HSS; mean BMI at the beginning of the study = 13.6; mean duration of illness = 5.1 years) vs. nine with less severe symptoms (LSS; mean BMI = 16.2; mean duration of illness = 3.7 years). During the course of treatment, serum leptin concentrations were assessed weekly while weight (BMI) was assessed twice per week. Concomitantly, psychological variables were obtained by means of electronic diaries. Unconditional linear growth models were calculated to evaluate the temporal course of leptin in relation to BMI. For HSS patients, two phases of treatment (BMI < 16 and BMI ≥ 16 kg/m2) were investigated.ResultsLeptin increased significantly with BMI in both groups of patients. For HSS patients, the increase of leptin in the first treatment phase did not predict later increases in BMI. Furthermore, the relationship of leptin and psychological factors was modulated by symptom severity. In HSS patients, higher leptin levels were associated with greater feelings of depression, anxiety, and stress whereas in LSS patients a higher leptin level showed the trend to be associated with lower psychological symptom burden.ConclusionsOur results suggest that leptin changes are differently associated with weight gain and psychological symptoms depending on the severity of starvation.

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Section: Introductioncontrasting

confidence: 63%

Section: Discussionmentioning

confidence: 77%

Section: Introductionmentioning

confidence: 99%

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Time Course of Leptin in Patients with Anorexia Nervosa during Inpatient Treatment: Longitudinal Relationships to BMI and Psychological Factors

Stroe-Kunold¹,

Buckert²,

Friederich³

et al. 2016

PLoS ONE

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“…Withdrawal of leptin during weight loss reduces its counterregulation of insulin actions, increases the sensitivity of the brain reward substrates to locomotor, olfactory, and gustatory rewards and increases the efficiency of insulin actions leading to lipogenesis and recovery of depleted body energy reservoirs. Leptin administration to underweight humans and animals suppresses the motivation to eat [305] , insulin metabolic efficiency [203,204,305] , and motivation for spontaneous locomotion [306][307][308][309] . With body mass loss and declines in leptin and insulin concentration, increased parasympathetic activation and sensitivities of tissues to insulin and leptin action facilitate efficient energy storage.…”

Section: Body Mass Lossmentioning

confidence: 99%

Counterregulation of insulin by leptin as key component of autonomic regulation of body weight

Borer¹

2014

WJD

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A re-examination of the mechanism controlling eating, locomotion, and metabolism prompts formulation of a new explanatory model containing five features: a coordinating joint role of the (1) autonomic nervous system (ANS); (2) the suprachiasmatic (SCN) master clock in counterbalancing parasympathetic digestive and absorptive functions and feeding with sympathetic locomotor and thermogenic energy expenditure within a circadian framework; (3) interaction of the ANS/SCN command with brain substrates of reward encompassing dopaminergic projections to ventral striatum and limbic and cortical forebrain. These drive the nonhomeostatic feeding and locomotor motivated behaviors in interaction with circulating ghrelin and lateral hypothalamic neurons signaling through melanin concentrating hormone and orexin-hypocretin peptides; (4) counterregulation of insulin by leptin of both gastric and adipose tissue origin through: potentiation by leptin of cholecystokinin-mediated satiation, inhibition of insulin secretion, suppression of insulin lipogenesis by leptin lipolysis, and modulation of peripheral tissue and brain sensitivity to insulin action. Thus weight-loss induced hypoleptimia raises insulin sensitivity and promotes its parasympathetic anabolic actions while obesity-induced hyperleptinemia supresses insulin lipogenic action; and (5) inhibition by leptin of bone mineral accrual suggesting that leptin may contribute to the maintenance of stability of skeletal, lean-body, as well as adipose tissue masses.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Insulin; Leptin; Weight regulation; Autonomic; Circadian Core tip: The novel proposal for the mechanism of body weight regulation deals with all three components of body mass: bone, lean tissue, and fat depots. It attributes the central control of counterbalancing energy expenditure and intake to an autonomic nervous systemcircadian clock command center that encompases brain reward substrates, lateral hypothalamic peptidergic circuits and areas of the cortex. The nonhomeostatic character of feeding and locomotion is driven and controlled by the reward circuits and modulated by shifts in insulin sensitivity induced by counterregulation by leptin of insulin as weight deviates between underweight and overweight and alters basal leptin concentrations.Borer KT. Counterregulation of insulin by leptin as key component of autonomic regulation of body weight. World J Diabetes 2014; 5(5): 606-629 Available from:

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“…Both findings indicate that hyperactivity in patients with anorexia nervosa is not necessarily a result of the patients' intention to prevent restoration of normal weight, but may very well represent an endocrinologically induced behaviour. Indeed, we have speculated that excessive hyperactivity (and potentially other behaviours and cognitions) in these patients may be amenable to treatment with recombinant leptin [7].…”

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confidence: 99%

Leptin treatment of patients with anorexia nervosa? The urgent need for initiation of clinical studies

Cited by 25 publications

References 25 publications

Time Course of Leptin in Patients with Anorexia Nervosa during Inpatient Treatment: Longitudinal Relationships to BMI and Psychological Factors

Time Course of Leptin in Patients with Anorexia Nervosa during Inpatient Treatment: Longitudinal Relationships to BMI and Psychological Factors

Counterregulation of insulin by leptin as key component of autonomic regulation of body weight

Anorexia nervosa through the looking glass of the draft ICD-11 diagnostic criteria: a disorder in transition

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