Limits...
Regulation of systemic energy homeostasis by serotonin in adipose tissues.

Oh CM, Namkung J, Go Y, Shong KE, Kim K, Kim H, Park BY, Lee HW, Jeon YH, Song J, Shong M, Yadav VK, Karsenty G, Kajimura S, Lee IK, Park S, Kim H - Nat Commun (2015)

Bottom Line: Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT).Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes.These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

View Article: PubMed Central - PubMed

Affiliation: BioMedical Research Center (E7) 8104, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

ABSTRACT
Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

Show MeSH

Related in: MedlinePlus

LP-533401 protects against diet-induced obesity and increased BAT activity.Mice were treated orally with vehicle or LP-533401 (30 mg kg−1) and fed an SCD or HFD for 14 weeks from 8 weeks of age. (a) Growth curves of vehicle- or LP-533401-treated mice fed an HFD. n=5 mice per group. *P<0.05, **P<0.01 and ***P<0.001 versus HFD+LP-533401 by Student's t-test. (b) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting n=4 mice per group. *P<0.05 and **P<0.01 versus HFD+LP-533401 by Student's t-test. (c) Representative haematoxylin and eosin (H&E) images of BAT of vehicle- or LP-533401-treated mice. Scale bar, 20 μm. (d) Expression of thermogenesis-related genes in BAT was assessed by quantitative reverse transcriptase–PCR (qRT–PCR). n=4 mice per group. *P<0.05 versus vehicle by Student's t-test. All data are presented as the mean±s.e.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4403443&req=5

f4: LP-533401 protects against diet-induced obesity and increased BAT activity.Mice were treated orally with vehicle or LP-533401 (30 mg kg−1) and fed an SCD or HFD for 14 weeks from 8 weeks of age. (a) Growth curves of vehicle- or LP-533401-treated mice fed an HFD. n=5 mice per group. *P<0.05, **P<0.01 and ***P<0.001 versus HFD+LP-533401 by Student's t-test. (b) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting n=4 mice per group. *P<0.05 and **P<0.01 versus HFD+LP-533401 by Student's t-test. (c) Representative haematoxylin and eosin (H&E) images of BAT of vehicle- or LP-533401-treated mice. Scale bar, 20 μm. (d) Expression of thermogenesis-related genes in BAT was assessed by quantitative reverse transcriptase–PCR (qRT–PCR). n=4 mice per group. *P<0.05 versus vehicle by Student's t-test. All data are presented as the mean±s.e.

Mentions: To exclude the possibility that anti-obesity effects of PCPA might be related to the inhibition of 5-HT synthesis in the brain, we have tested peripheral Tph inhibitior, LP-533401, which cannot cross the blood–brain barrier14. Mice treated with LP-533401 showed reduced weight gain and improved glucose tolerance compared with control mice under an HFD (Fig. 4a,b). The BAT of LP-533401-treated mice displayed similar histological changes to those observed in PCPA-treated mice after an HFD feeding (Fig. 4c). The BAT of LP-533401-treated mice also showed increased thermogenic gene expressions (Fig. 4d). Taken together, our data suggested that the inhibition of peripheral Tph1 increased energy expenditure by increasing thermogenic activity of BAT and iWAT.


Regulation of systemic energy homeostasis by serotonin in adipose tissues.

Oh CM, Namkung J, Go Y, Shong KE, Kim K, Kim H, Park BY, Lee HW, Jeon YH, Song J, Shong M, Yadav VK, Karsenty G, Kajimura S, Lee IK, Park S, Kim H - Nat Commun (2015)

LP-533401 protects against diet-induced obesity and increased BAT activity.Mice were treated orally with vehicle or LP-533401 (30 mg kg−1) and fed an SCD or HFD for 14 weeks from 8 weeks of age. (a) Growth curves of vehicle- or LP-533401-treated mice fed an HFD. n=5 mice per group. *P<0.05, **P<0.01 and ***P<0.001 versus HFD+LP-533401 by Student's t-test. (b) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting n=4 mice per group. *P<0.05 and **P<0.01 versus HFD+LP-533401 by Student's t-test. (c) Representative haematoxylin and eosin (H&E) images of BAT of vehicle- or LP-533401-treated mice. Scale bar, 20 μm. (d) Expression of thermogenesis-related genes in BAT was assessed by quantitative reverse transcriptase–PCR (qRT–PCR). n=4 mice per group. *P<0.05 versus vehicle by Student's t-test. All data are presented as the mean±s.e.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4403443&req=5

f4: LP-533401 protects against diet-induced obesity and increased BAT activity.Mice were treated orally with vehicle or LP-533401 (30 mg kg−1) and fed an SCD or HFD for 14 weeks from 8 weeks of age. (a) Growth curves of vehicle- or LP-533401-treated mice fed an HFD. n=5 mice per group. *P<0.05, **P<0.01 and ***P<0.001 versus HFD+LP-533401 by Student's t-test. (b) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting n=4 mice per group. *P<0.05 and **P<0.01 versus HFD+LP-533401 by Student's t-test. (c) Representative haematoxylin and eosin (H&E) images of BAT of vehicle- or LP-533401-treated mice. Scale bar, 20 μm. (d) Expression of thermogenesis-related genes in BAT was assessed by quantitative reverse transcriptase–PCR (qRT–PCR). n=4 mice per group. *P<0.05 versus vehicle by Student's t-test. All data are presented as the mean±s.e.
Mentions: To exclude the possibility that anti-obesity effects of PCPA might be related to the inhibition of 5-HT synthesis in the brain, we have tested peripheral Tph inhibitior, LP-533401, which cannot cross the blood–brain barrier14. Mice treated with LP-533401 showed reduced weight gain and improved glucose tolerance compared with control mice under an HFD (Fig. 4a,b). The BAT of LP-533401-treated mice displayed similar histological changes to those observed in PCPA-treated mice after an HFD feeding (Fig. 4c). The BAT of LP-533401-treated mice also showed increased thermogenic gene expressions (Fig. 4d). Taken together, our data suggested that the inhibition of peripheral Tph1 increased energy expenditure by increasing thermogenic activity of BAT and iWAT.

Bottom Line: Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT).Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes.These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

View Article: PubMed Central - PubMed

Affiliation: BioMedical Research Center (E7) 8104, Graduate School of Medical Science and Engineering, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.

ABSTRACT
Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

Show MeSH
Related in: MedlinePlus