Diabetes Metab J.  2016 Apr;40(2):89-98. 10.4093/dmj.2016.40.2.89.

Serotonin as a New Therapeutic Target for Diabetes Mellitus and Obesity

• Oh CM
• Park S
• Kim H

• KMID: 2162080
• DOI: http://doi.org/10.4093/dmj.2016.40.2.89

Abstract

Serotonin (5-hydroxytryptamine [5-HT]) is a monoamine that has various functions in both neuronal and non-neuronal systems. In the central nervous system, 5-HT regulates mood and feeding behaviors as a neurotransmitter. Thus, there have been many trials aimed at increasing the activity of 5-HT in the central nervous system, and some of the developed methods are already used in the clinical setting as anti-obesity drugs. Unfortunately, some drugs were withdrawn due to the development of unwanted peripheral side effects, such as valvular heart disease and pulmonary hypertension. Recent studies revealed that peripheral 5-HT plays an important role in metabolic regulation in peripheral tissues, where it suppresses adaptive thermogenesis in brown adipose tissue. Inhibition of 5-HT synthesis reduced the weight gain and improved the metabolic dysfunction in a diet-induced obesity mouse model. Genome-wide association studies also revealed genetic associations between the serotonergic system and obesity. Several genetic polymorphisms in tryptophan hydroxylase and 5-HT receptors were shown to have strong associations with obesity. These results support the clinical significance of the peripheral serotonergic system as a therapeutic target for obesity and diabetes.

Keyword

Diabetes mellitus; Obesity; Serotonin

MeSH Terms

Adipose Tissue, Brown
Animals
Anti-Obesity Agents
Central Nervous System
Diabetes Mellitus*
Feeding Behavior
Genome-Wide Association Study
Heart Valve Diseases
Hypertension, Pulmonary
Mice
Neurons
Neurotransmitter Agents
Obesity*
Polymorphism, Genetic
Receptors, Serotonin
Serotonin*
Thermogenesis
Tryptophan Hydroxylase
Weight Gain
Anti-Obesity Agents
Neurotransmitter Agents
Receptors, Serotonin
Serotonin
Tryptophan Hydroxylase

Figure

• 

  Fig. 1 Roles of 5-hydroxytryptamine (5-HT) on metabolic organs. Central 5-HT regulates appetite and controls metabolic organs through sympathetic/parasympathetic nervous system. Peripheral 5-HT regulates glucose metabolism, insulin resistance and energy expenditure in an autocrine/paracrine or endocrine manner. TPH, tryptophan hydroxylase; HTR, 5-HT receptor; β-AR β-adrenergic receptor; BAT, brown adipose tissue; WAT, white adipose tissue.

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