Pharmacological treatment strategies for patients with monogenic obesity

2020 ◽  
Vol 33 (8) ◽  
pp. 967-973
Author(s):  
Peter Kühnen ◽  
Susanna Wiegand ◽  
Heike Biebermann
Keyword(s):  
Body Weight ◽  
Pharmacological Treatment ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Research Progress ◽  
Weight Regulation ◽  
Body Weight Regulation ◽  
Melanocortin Signaling ◽  
Recent Research Progress

AbstractThe leptin melanocortin signaling pathway is playing a pivotal role for body weight regulation. Genetic defects within this cascade are leading to severe hyperphagia and early onset obesity. In most cases, due to persistent hyperphagia the affected patients are not able to stabilize body weight for a longer period of time with conservative treatment strategies based on lifestyle interventions. Therefore, it is of importance to implement alternative treatment options for these patients. This review provides an overview about the published pharmacological treatment attempts in respect to monogenic forms of obesity and summarizes recent research progress about the role of MC4R signaling and POMC derivatives for body weight regulation.

Basic mechanisms and potential for treatment of weight and eating disorders

2020 ◽  
pp. 1048-1058 ◽  
Author(s):  
Johannes Hebebrand ◽  
Jochen Antel ◽  
Beate Herpertz-Dahlmann
Keyword(s):  
Body Weight ◽  
Drug Targets ◽  
Treatment Options ◽  
Treatment Strategies ◽  
Current Treatment ◽  
Weight Regulation ◽  
Body Weight Regulation ◽  
Lost To Follow Up ◽  
Lines Of Evidence

Eating and weight disorders frequently persist over time despite extensive therapeutic efforts. Both high dropout and lost-to-follow-up rates observed in randomized controlled trials indicate that many patients are not satisfied by current treatment options. Particularly, obesity-related research has underscored the multitude and complexity of aetiological factors involved in body weight regulation. Multiple lines of evidence point to an intertwining of the regulation of energy intake and expenditure with other somatic and mental functions. The elucidation of monogenic forms of obesity has led to the identification of drug targets, which may prove helpful for the treatment of eating and weight disorders. This chapter discusses potential treatment strategies for these disorders, based on our greatly improved understanding of the underlying neurobiological mechanisms and the function of the microbiome in body weight regulation.

scholarly journals Role of GABA Release From Leptin Receptor-Expressing Neurons in Body Weight Regulation

Endocrinology ◽  
2012 ◽  
Vol 153 (5) ◽  
pp. 2223-2233 ◽  
Author(s):  
Yuanzhong Xu ◽  
William G. O'Brien ◽  
Cheng-Chi Lee ◽  
Martin G. Myers ◽  
Qingchun Tong
Keyword(s):  
Body Weight ◽  
Food Intake ◽  
Leptin Receptor ◽  
Gaba Release ◽  
Neuron Activity ◽  
Chow Diet ◽  
Weight Regulation ◽  
Body Weight Regulation ◽  
The Brain

It is well established that leptin regulates energy balance largely through isoform B leptin receptor-expressing neurons (LepR neurons) in the brain and that leptin activates one subset of LepR neurons (leptin-excited neurons) while inhibiting the other (leptin-inhibited neurons). However, the neurotransmitters released from LepR neurons that mediate leptin action in the brain are not well understood. Previous results demonstrate that leptin mainly acts on γ-aminobutyric acid (GABA)ergic neurons to reduce body weight, and that leptin activates proopiomelanocortin neuron activity by reducing GABA release onto these neurons, suggesting a body weight-promoting role for GABA released from leptin-inhibited neurons. To directly examine the role of GABA release from LepR neurons in body weight regulation, mice with disruption of GABA release specifically from LepR neurons were generated by deletion of vesicular GABA transporter in LepR neurons. Interestingly, these mice developed mild obesity on chow diet and were sensitive to diet-induced obesity, which were associated with higher food intake and lower energy expenditure. Moreover, these mice showed blunted responses in both food intake and body weight to acute leptin administration. These results demonstrate that GABA plays an important role in mediating leptin action. In combination with the previous studies that leptin reduces GABA release onto proopiomelanocortin neurons through leptin-inhibited neurons and that disruption of GABA release from agouti gene-related protein neurons, one subset of LepR-inhibited neurons, leads to a lean phenotype, our results suggest that, under our experimental conditions, GABA release from leptin-excited neuron dominates over leptin-inhibited ones.

“The role of melanocortins in body weight regulation: opportunities for the treatment of obesity”

2002 ◽  
Vol 450 (1) ◽  
pp. 93-109 ◽  
Author(s):  
Douglas J. MacNeil ◽  
Andrew D. Howard ◽  
Xiaoming Guan ◽  
Tung M. Fong ◽  
Ravi P. Nargund ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Regulation ◽  
Body Weight Regulation ◽  
Treatment Of Obesity

scholarly journals Metabolic Diseases: the Environment Determines the Odds, Even for Genes

Physiology ◽  
2002 ◽  
Vol 17 (3) ◽  
pp. 115-121 ◽  
Author(s):  
Ingrid Schmidt
Keyword(s):  
Body Weight ◽  
Control Systems ◽  
Environmental Impacts ◽  
Metabolic Diseases ◽  
Well Being ◽  
Weight Regulation ◽  
Body Weight Regulation

The odds for well-being or illness are determined by the interplay of genetic and environmental impacts. In this review, normal and disturbed body weight regulation are used to demonstrate the role of integrative bioresearch in bridging the gap between identified genotypes and an understanding of the functions of redundant and plastic control systems underlying phenotypes.

scholarly journals Role of Energy Excretion in Human Body Weight Regulation

2020 ◽  
Vol 31 (10) ◽  
pp. 705-708 ◽  
Author(s):  
Jens Lund ◽  
Zachary Gerhart-Hines ◽  
Christoffer Clemmensen
Keyword(s):  
Body Weight ◽  
Human Body ◽  
Weight Regulation ◽  
Body Weight Regulation
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