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Small molecules for fat combustion: targeting obesity.

Jingxin Liu1, Yitao Wang1, Ligen Lin1

  • 1State Key Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa 999078, Macau, China.

Acta Pharmaceutica Sinica. B
|April 13, 2019
PubMed
Summary

Obesity is a growing global health concern. This review explores how brown adipose tissue (BAT) and beige cells generate heat (thermogenesis) and discusses regulators that may offer new obesity treatments.

Keywords:
AKT, protein kinase BALDH9, aldehyde dehydrogenase 9AMPK, AMP-activated protein kinaseATP, adenosine triphosphateBA, bile acidsBAT, brown adipose tissueBMP8b, bone morphogenetic protein 8bBeige cellsBrown adipose tissueC/EBPα, CCAAT/enhancer binding protein αCLA, cis-12 conjugated linoleic acidCRABP-II, cellular RA binding protein type IICRE, cAMP response elementCidea, cell death-inducing DNA fragmentation factor α-like effector ADio2, iodothyronine deiodinase type 2ERE, estrogen response elementERs, estrogen receptorsFAS, fatty acid synthaseFGF21, fibroblast growth factor 21GPCRs, G protein-coupled receptorsHFD, high fat dietLXR, liver X receptorsMAPK, mitogen-activated protein kinaseOXPHOS, oxidative phosphorylationObesityPDEs, phosphodiesterasesPET-CT, positron emission tomography combined with computed tomographyPGC-1α, peroxisome proliferator-activated receptor γ coactivator 1-αPKA, protein kinase APPARs, peroxisome proliferator-activated receptorsPPREs, peroxisome proliferator response elementsPRDM16, PR domain containing 16PTP1B, protein-tyrosine phosphatase 1BPXR, pregnane X receptorRA, retinoic acidRAR, RA receptorRARE, RA response elementRMR, resting metabolic rateRXR, retinoid X receptorSIRT1, silent mating type information regulation 2 homolog 1SNS, sympathetic nervous systemTFAM, mitochondrial transcription factor ATMEM26, transmembrane protein 26TRPs, transient receptor potential cation channelsThermogenesisUCP1, uncoupling protein 1Uncoupling protein 1VDR, vitamin D receptorVDRE, VDR response elementsWAT, white adipose tissuecAMP, cyclic adenosine monophosphatecGMP, cyclic guanosine monophosphateβ3-AR, β3-adrenergic receptor

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Area of Science:

  • Metabolism and Endocrinology
  • Cell Biology
  • Pharmacology

Background:

  • Rising global obesity rates increase risks for type 2 diabetes, cardiovascular diseases, and cancer.
  • Current obesity treatments, like lipase inhibitors and appetite suppressors, have limited efficacy.
  • Brown adipose tissue (BAT) and beige cells dissipate energy as heat (non-shivering thermogenesis), counteracting obesity.

Purpose of the Study:

  • To review the physiology of thermogenesis and the role of BAT and beige cells in combating obesity.
  • To summarize thermogenic regulators targeting various pathways (GPCRs, TRPs, nuclear receptors).
  • To present advances in clinical trials for obesity treatment.

Main Methods:

  • Comprehensive literature review of thermogenesis and its regulators.
  • Analysis of the role of BAT and beige cells in energy homeostasis.
  • Summary of identified thermogenic regulators and clinical trial progress.

Main Results:

  • BAT and beige cell activity is inversely correlated with obesity.
  • Numerous thermogenic regulators have been identified across diverse pathways.
  • Clinical trials are exploring the therapeutic potential of these regulators.

Conclusions:

  • Thermogenesis via BAT and beige cells offers a promising strategy for weight management.
  • Identified thermogenic regulators hold significant potential for developing novel anti-obesity therapies.
  • Further research into thermogenic regulators could yield effective lead compounds for obesity treatment.