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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.

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PCPA protects against diet-induced obesity.(a) Growth curves of vehicle- or PCPA-treated mice fed an SCD or HFD. n=4 mice per group. *P<0.05 versus HFD+PCPA by Student's t-test. (b) Gross images of vehicle- or PCPA-treated mice after 10 weeks of HFD feeding. (c) Intraperitoneal glucose tolerance test (IPGTT) after fasting for 16 h. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (e) The metabolic rates of vehicle- or PCPA-treated mice after 6 weeks of HFD feeding. The metabolic parameters were measured using an 8-chamber Oxymax system. Mice were acclimatized to cages for 24 h and data were collected for an additional 48 h. n=4 mice per group. *P<0.05 versus vehicle by Student's t-test. All data are presented as the mean±s.e.
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f1: PCPA protects against diet-induced obesity.(a) Growth curves of vehicle- or PCPA-treated mice fed an SCD or HFD. n=4 mice per group. *P<0.05 versus HFD+PCPA by Student's t-test. (b) Gross images of vehicle- or PCPA-treated mice after 10 weeks of HFD feeding. (c) Intraperitoneal glucose tolerance test (IPGTT) after fasting for 16 h. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (e) The metabolic rates of vehicle- or PCPA-treated mice after 6 weeks of HFD feeding. The metabolic parameters were measured using an 8-chamber Oxymax system. Mice were acclimatized to cages for 24 h and data were collected for an additional 48 h. 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: We hypothesized that if peripheral 5-HT has opposite effects to central 5-HT in the regulation of body weight, long-term systemic inhibition of 5-HT synthesis may reduce body weight or the degree of weight gain by an HFD. In this regard, mice were fed an HFD and administered PCPA by intraperitoneal injection for 12 weeks from 11 weeks of age. PCPA-treated mice ate more food than control mice during the first week of HFD, but their food intake became comparable to control mice from the second week throughout the HFD period. These changes of eating patterns matched well with previous reports9. As a result of the systemic inhibition of 5-HT synthesis, PCPA-treated mice exhibited decreased body weight gain on an HFD (Fig. 1a) and their visceral fat mass was reduced (Fig. 1b), although they showed similar body weight on a standard chow diet (SCD).


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)

PCPA protects against diet-induced obesity.(a) Growth curves of vehicle- or PCPA-treated mice fed an SCD or HFD. n=4 mice per group. *P<0.05 versus HFD+PCPA by Student's t-test. (b) Gross images of vehicle- or PCPA-treated mice after 10 weeks of HFD feeding. (c) Intraperitoneal glucose tolerance test (IPGTT) after fasting for 16 h. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (e) The metabolic rates of vehicle- or PCPA-treated mice after 6 weeks of HFD feeding. The metabolic parameters were measured using an 8-chamber Oxymax system. Mice were acclimatized to cages for 24 h and data were collected for an additional 48 h. 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

f1: PCPA protects against diet-induced obesity.(a) Growth curves of vehicle- or PCPA-treated mice fed an SCD or HFD. n=4 mice per group. *P<0.05 versus HFD+PCPA by Student's t-test. (b) Gross images of vehicle- or PCPA-treated mice after 10 weeks of HFD feeding. (c) Intraperitoneal glucose tolerance test (IPGTT) after fasting for 16 h. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (d) Intraperitoneal insulin tolerance test (IPITT) after 4 h fasting. n=3 mice per group. *P<0.05 versus HFD by Student's t-test. (e) The metabolic rates of vehicle- or PCPA-treated mice after 6 weeks of HFD feeding. The metabolic parameters were measured using an 8-chamber Oxymax system. Mice were acclimatized to cages for 24 h and data were collected for an additional 48 h. 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: We hypothesized that if peripheral 5-HT has opposite effects to central 5-HT in the regulation of body weight, long-term systemic inhibition of 5-HT synthesis may reduce body weight or the degree of weight gain by an HFD. In this regard, mice were fed an HFD and administered PCPA by intraperitoneal injection for 12 weeks from 11 weeks of age. PCPA-treated mice ate more food than control mice during the first week of HFD, but their food intake became comparable to control mice from the second week throughout the HFD period. These changes of eating patterns matched well with previous reports9. As a result of the systemic inhibition of 5-HT synthesis, PCPA-treated mice exhibited decreased body weight gain on an HFD (Fig. 1a) and their visceral fat mass was reduced (Fig. 1b), although they showed similar body weight on a standard chow diet (SCD).

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