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CNS-targeting pharmacological interventions for the metabolic syndrome
Kerstin Stemmer, … , Paul T. Pfluger, Matthias H. Tschöp
Kerstin Stemmer, … , Paul T. Pfluger, Matthias H. Tschöp
Published August 5, 2019
Citation Information: J Clin Invest. 2019;129(10):4058-4071. https://doi.org/10.1172/JCI129195.
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Review Series Article has an altmetric score of 9

CNS-targeting pharmacological interventions for the metabolic syndrome

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Abstract

The metabolic syndrome (MetS) encompasses medical conditions such as obesity, hyperglycemia, high blood pressure, and dyslipidemia that are major drivers for the ever-increasing prevalence of type 2 diabetes, cardiovascular diseases, and certain types of cancer. At the core of clinical strategies against the MetS is weight loss, induced by bariatric surgery, lifestyle changes based on calorie reduction and exercise, or pharmacology. This Review summarizes the past, current, and future efforts of targeting the MetS by pharmacological agents. Major emphasis is given to drugs that target the CNS as a key denominator for obesity and its comorbid sequelae.

Authors

Kerstin Stemmer, Timo D. Müller, Richard D. DiMarchi, Paul T. Pfluger, Matthias H. Tschöp

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Figure 1

Homeostatic and hedonic control centers in the brain.

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Homeostatic and hedonic control centers in the brain.
Drugs targeting co...
Drugs targeting control of metabolism by the CNS act mainly via homeostatic and hedonic control centers that govern feeding behaviors, energy and glucose homeostasis, and body weight. The related brain areas are densely interconnected, and receive direct input from circulating nutrients such as glucose or fatty acids, peripheral neuronal networks, and hormonal satiation signals such as GLP-1 or amylin, or hormonal adiposity signals such as leptin. Within the homeostatic and hedonic control centers, the peripheral signals are integrated with sensory input, past experiences, and cues arising from the prevailing stress situation, emotional context, and mood. Ultimately, the signals converge in nuclei such as the hypothalamic paraventricular nucleus and lateral hypothalamus, and induce both adaptations to our ingestive behavior and brain stem–mediated changes to peripheral organ functions and our control of energy and glucose metabolism. AP, area postrema; ARC, arcuate nucleus; FGF21, fibroblast growth factor 21; GI tract, gastrointestinal tract; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; LH, lateral hypothalamus; NAc, nucleus accumbens; NTS, nucleus of the solitary tract; PVN, paraventricular nucleus; PYY3-36, peptide YY 3-36; VTA, ventral tegmental area.

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ISSN: 0021-9738 (print), 1558-8238 (online)

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