Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance

Gina M. Leinninger; Darren M. Opland; Young Hwan Jo; Miro Faouzi; Lyndsay Christensen; Laura A. Cappellucci; Christopher J. Rhodes; Margaret E. Gnegy; Jill B. Becker; Emmanuel N. Pothos; Audrey F. Seasholtz; Robert C. Thompson; Martin G. Myers

doi:10.1016/j.cmet.2011.06.016

Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance

Gina M. Leinninger, Darren M. Opland, Young Hwan Jo, Miro Faouzi, Lyndsay Christensen, Laura A. Cappellucci, Christopher J. Rhodes, Margaret E. Gnegy, Jill B. Becker, Emmanuel N. Pothos, Audrey F. Seasholtz, Robert C. Thompson, Martin G. Myers

Medicine

Research output: Contribution to journal › Article › peer-review

270 Scopus citations

Abstract

Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb ^Nts neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection of LepRb ^Nts neurons with local orexin (OX) neurons and the ventral tegmental area (VTA), Nts-LepRbKO mice exhibit altered regulation of OX neurons and the mesolimbic DA system. Thus, LHA LepRb ^Nts neurons mediate physiologic leptin action on OX neurons and the mesolimbic DA system, and contribute importantly to the control of energy balance.

Original language	English (US)
Pages (from-to)	313-323
Number of pages	11
Journal	Cell metabolism
Volume	14
Issue number	3
DOIs	https://doi.org/10.1016/j.cmet.2011.06.016
State	Published - Sep 7 2011

ASJC Scopus subject areas

Physiology
Molecular Biology
Cell Biology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.cmet.2011.06.016

Cite this

Leinninger, G. M., Opland, D. M., Jo, Y. H., Faouzi, M., Christensen, L., Cappellucci, L. A., Rhodes, C. J., Gnegy, M. E., Becker, J. B., Pothos, E. N., Seasholtz, A. F., Thompson, R. C., & Myers, M. G. (2011). Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance. Cell metabolism, 14(3), 313-323. https://doi.org/10.1016/j.cmet.2011.06.016

@article{7e91d66c1e404c5a984b51ee674ea9d1,

title = "Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance",

abstract = "Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb Nts neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection of LepRb Nts neurons with local orexin (OX) neurons and the ventral tegmental area (VTA), Nts-LepRbKO mice exhibit altered regulation of OX neurons and the mesolimbic DA system. Thus, LHA LepRb Nts neurons mediate physiologic leptin action on OX neurons and the mesolimbic DA system, and contribute importantly to the control of energy balance.",

author = "Leinninger, {Gina M.} and Opland, {Darren M.} and Jo, {Young Hwan} and Miro Faouzi and Lyndsay Christensen and Cappellucci, {Laura A.} and Rhodes, {Christopher J.} and Gnegy, {Margaret E.} and Becker, {Jill B.} and Pothos, {Emmanuel N.} and Seasholtz, {Audrey F.} and Thompson, {Robert C.} and Myers, {Martin G.}",

note = "Funding Information: We thank Amylin Pharmaceuticals (San Diego, CA) for the generous gift of leptin, Dr. Streamson Chua for the gift of Lepr fl mice, and members of the Myers lab for helpful discussions. Core support was provided by the Michigan Diabetes Research and Training Center. Supported by grants from the American Diabetes Association and American Heart Association (M.G.M.), the National Institutes of Health (M.G.M., C.J.R., J.B.B., E.N.P.), and the Obesity Society (G.M.L.). ",

year = "2011",

month = sep,

day = "7",

doi = "10.1016/j.cmet.2011.06.016",

language = "English (US)",

volume = "14",

pages = "313--323",

journal = "Cell metabolism",

issn = "1550-4131",

publisher = "Cell Press",

number = "3",

}

TY - JOUR

T1 - Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance

AU - Leinninger, Gina M.

AU - Opland, Darren M.

AU - Jo, Young Hwan

AU - Faouzi, Miro

AU - Christensen, Lyndsay

AU - Cappellucci, Laura A.

AU - Rhodes, Christopher J.

AU - Gnegy, Margaret E.

AU - Becker, Jill B.

AU - Pothos, Emmanuel N.

AU - Seasholtz, Audrey F.

AU - Thompson, Robert C.

AU - Myers, Martin G.

N1 - Funding Information: We thank Amylin Pharmaceuticals (San Diego, CA) for the generous gift of leptin, Dr. Streamson Chua for the gift of Lepr fl mice, and members of the Myers lab for helpful discussions. Core support was provided by the Michigan Diabetes Research and Training Center. Supported by grants from the American Diabetes Association and American Heart Association (M.G.M.), the National Institutes of Health (M.G.M., C.J.R., J.B.B., E.N.P.), and the Obesity Society (G.M.L.).

PY - 2011/9/7

Y1 - 2011/9/7

N2 - Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb Nts neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection of LepRb Nts neurons with local orexin (OX) neurons and the ventral tegmental area (VTA), Nts-LepRbKO mice exhibit altered regulation of OX neurons and the mesolimbic DA system. Thus, LHA LepRb Nts neurons mediate physiologic leptin action on OX neurons and the mesolimbic DA system, and contribute importantly to the control of energy balance.

AB - Leptin acts on leptin receptor (LepRb)-expressing neurons throughout the brain, but the roles for many populations of LepRb neurons in modulating energy balance and behavior remain unclear. We found that the majority of LepRb neurons in the lateral hypothalamic area (LHA) contain neurotensin (Nts). To investigate the physiologic role for leptin action via these LepRb Nts neurons, we generated mice null for LepRb specifically in Nts neurons (Nts-LepRbKO mice). Nts-LepRbKO mice demonstrate early-onset obesity, modestly increased feeding, and decreased locomotor activity. Furthermore, consistent with the connection of LepRb Nts neurons with local orexin (OX) neurons and the ventral tegmental area (VTA), Nts-LepRbKO mice exhibit altered regulation of OX neurons and the mesolimbic DA system. Thus, LHA LepRb Nts neurons mediate physiologic leptin action on OX neurons and the mesolimbic DA system, and contribute importantly to the control of energy balance.

UR - http://www.scopus.com/inward/record.url?scp=80052707655&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052707655&partnerID=8YFLogxK

U2 - 10.1016/j.cmet.2011.06.016

DO - 10.1016/j.cmet.2011.06.016

M3 - Article

C2 - 21907138

AN - SCOPUS:80052707655

SN - 1550-4131

VL - 14

SP - 313

EP - 323

JO - Cell metabolism

JF - Cell metabolism

IS - 3

ER -

Leptin action via neurotensin neurons controls orexin, the mesolimbic dopamine system and energy balance

Abstract

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this