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

Htr3a KO mice are resistant to diet-induced obesity.(a) Growth curves of Htr3a KO mice and their WT littermates fed an SCD or HFD. n=4 mice per group. **P<0.01 versus WT, HFD by Student's t-test. (b) Gross images of Htr3a KO mice fed an SCD or HFD for 6 weeks beginning at 8 weeks of age. (c) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting. n=4 mice per group. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=4 mice per group. **P<0.01 and ***P<0.001 versus WT, HFD by Student's t-test. (e) The metabolic rates of Htr3a KO mice and their WT littermates after 6 weeks of HFD feeding. n=4 mice per group. ***P<0.001 versus WT 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

f7: Htr3a KO mice are resistant to diet-induced obesity.(a) Growth curves of Htr3a KO mice and their WT littermates fed an SCD or HFD. n=4 mice per group. **P<0.01 versus WT, HFD by Student's t-test. (b) Gross images of Htr3a KO mice fed an SCD or HFD for 6 weeks beginning at 8 weeks of age. (c) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting. n=4 mice per group. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=4 mice per group. **P<0.01 and ***P<0.001 versus WT, HFD by Student's t-test. (e) The metabolic rates of Htr3a KO mice and their WT littermates after 6 weeks of HFD feeding. n=4 mice per group. ***P<0.001 versus WT by Student's t-test. All data are presented as the mean±s.e.

Mentions: Htr3a KO mice were fed an HFD for 6 weeks from 10 weeks of age and analysed their metabolic phenotypes (Supplementary Fig. 4a). As shown in Fig. 7, Htr3a KO mice were resistant to HFD-induced obesity (Fig. 7a,b). However, glucose tolerance was not improved in Htr3a KO mice, despite the improved insulin sensitivity (Fig. 7c,d). Defective insulin secretion in Htr3a KO mice can explain the discrepancy between glucose tolerance and insulin sensitivity26. As expected, Htr3a KO mice exhibited increased oxygen consumption and heat production compared with their WT littermates (Fig. 7e and Supplementary Fig. 4b). HFD-fed Htr3a KO mice did not exhibit enlarged unilocular lipid droplets in the BAT, which were observed in the BAT of their WT littermates after HFD feeding (Fig. 8a). Thermogenic gene expressions also increased in BAT of Htr3a KO mice (Fig. 8b). Furthermore, mitochondrial biogenesis was increased in BAT of Htr3a KO mice (Fig. 8c,d). These data suggested that the metabolic and histological changes observed in HFD-fed Tph1 AFKO mice could be attributed to the reduced Htr3 activity in BAT. However, WAT of Htr3a KO mice did not exhibit similar changes to Tph1 AFKO after HFD, suggesting the more selective effects of Htr3 in BAT (Figs 7b and 8e).


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)

Htr3a KO mice are resistant to diet-induced obesity.(a) Growth curves of Htr3a KO mice and their WT littermates fed an SCD or HFD. n=4 mice per group. **P<0.01 versus WT, HFD by Student's t-test. (b) Gross images of Htr3a KO mice fed an SCD or HFD for 6 weeks beginning at 8 weeks of age. (c) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting. n=4 mice per group. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=4 mice per group. **P<0.01 and ***P<0.001 versus WT, HFD by Student's t-test. (e) The metabolic rates of Htr3a KO mice and their WT littermates after 6 weeks of HFD feeding. n=4 mice per group. ***P<0.001 versus WT 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

f7: Htr3a KO mice are resistant to diet-induced obesity.(a) Growth curves of Htr3a KO mice and their WT littermates fed an SCD or HFD. n=4 mice per group. **P<0.01 versus WT, HFD by Student's t-test. (b) Gross images of Htr3a KO mice fed an SCD or HFD for 6 weeks beginning at 8 weeks of age. (c) Intraperitoneal glucose tolerance test (IPGTT) after 16 h fasting. n=4 mice per group. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=4 mice per group. **P<0.01 and ***P<0.001 versus WT, HFD by Student's t-test. (e) The metabolic rates of Htr3a KO mice and their WT littermates after 6 weeks of HFD feeding. n=4 mice per group. ***P<0.001 versus WT by Student's t-test. All data are presented as the mean±s.e.
Mentions: Htr3a KO mice were fed an HFD for 6 weeks from 10 weeks of age and analysed their metabolic phenotypes (Supplementary Fig. 4a). As shown in Fig. 7, Htr3a KO mice were resistant to HFD-induced obesity (Fig. 7a,b). However, glucose tolerance was not improved in Htr3a KO mice, despite the improved insulin sensitivity (Fig. 7c,d). Defective insulin secretion in Htr3a KO mice can explain the discrepancy between glucose tolerance and insulin sensitivity26. As expected, Htr3a KO mice exhibited increased oxygen consumption and heat production compared with their WT littermates (Fig. 7e and Supplementary Fig. 4b). HFD-fed Htr3a KO mice did not exhibit enlarged unilocular lipid droplets in the BAT, which were observed in the BAT of their WT littermates after HFD feeding (Fig. 8a). Thermogenic gene expressions also increased in BAT of Htr3a KO mice (Fig. 8b). Furthermore, mitochondrial biogenesis was increased in BAT of Htr3a KO mice (Fig. 8c,d). These data suggested that the metabolic and histological changes observed in HFD-fed Tph1 AFKO mice could be attributed to the reduced Htr3 activity in BAT. However, WAT of Htr3a KO mice did not exhibit similar changes to Tph1 AFKO after HFD, suggesting the more selective effects of Htr3 in BAT (Figs 7b and 8e).

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