title: Leptin and insulin act on POMC neurons to promote the browning of white fat.
abstract: The primary task of white adipose tissue (WAT) is the storage of lipids. However, "beige" adipocytes also exist in WAT. Beige adipocytes burn fat and dissipate the energy as heat, but their abundance is diminished in obesity. Stimulating beige adipocyte development, or WAT browning, increases energy expenditure and holds potential for combating metabolic disease and obesity. Here, we report that insulin and leptin act together on hypothalamic neurons to promote WAT browning and weight loss. Deletion of the phosphatases PTP1B and TCPTP enhanced insulin and leptin signaling in proopiomelanocortin neurons and prevented diet-induced obesity by increasing WAT browning and energy expenditure. The coinfusion of insulin plus leptin into the CNS or the activation of proopiomelanocortin neurons also increased WAT browning and decreased adiposity. Our findings identify a homeostatic mechanism for coordinating the status of energy stores, as relayed by insulin and leptin, with the central control of WAT browning.
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
authors.forename: Garron T
authors.initials: GT
authors.lastname: Dodd
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Decherf
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
authors.forename: Kim
authors.initials: K
authors.lastname: Loh
authors.affiliation: Department of Physiology, Monash University, Victoria 3800, Australia.
authors.forename: Stephanie E
authors.initials: SE
authors.lastname: Simonds
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
authors.forename: Florian
authors.initials: F
authors.lastname: Wiede
authors.affiliation: Department of Physiology, Monash University, Victoria 3800, Australia.
authors.forename: Eglantine
authors.initials: E
authors.lastname: Balland
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia.
authors.forename: Troy L
authors.initials: TL
authors.lastname: Merry
authors.affiliation: Pennington Biomedical Research Center, LSU Systems, Baton Rouge, LA 70808, USA.
authors.forename: Heike
authors.initials: H
authors.lastname: Münzberg
authors.affiliation: Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
authors.forename: Zhong-Yin
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Medicine, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02215, USA.
authors.forename: Barbara B
authors.initials: BB
authors.lastname: Kahn
authors.affiliation: Campbell Family Cancer Research Institute, Ontario Cancer Institute, Princess Margaret Hospital and Department of Medical Biophysics, University of Toronto, Toronto, ON M5G 2M9, Canada.
authors.forename: Benjamin G
authors.initials: BG
authors.lastname: Neel
authors.affiliation: Department of Animal Biology, School of Veterinary Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
authors.forename: Kendra K
authors.initials: KK
authors.lastname: Bence
authors.affiliation: Department of Physiology, Monash University, Victoria 3800, Australia.
authors.forename: Zane B
authors.initials: ZB
authors.lastname: Andrews
authors.affiliation: Department of Physiology, Monash University, Victoria 3800, Australia.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Cowley
authors.affiliation: Department of Biochemistry and Molecular Biology, Monash University, Victoria 3800, Australia. Electronic address: tony.tiganis@monash.edu.
authors.forename: Tony
authors.initials: T
authors.lastname: Tiganis
mesh_terms: D002001:Adipose Tissue, Brown / Q000378:metabolism*; D052436:Adipose Tissue, White / Q000378:metabolism*; D050154:Adiposity; D000818:Animals; D001833:Body Temperature Regulation; D007328:Insulin / Q000378:metabolism*; D020738:Leptin / Q000378:metabolism*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000378:metabolism; D009765:Obesity / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1 / Q000378:metabolism; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2 / Q000378:metabolism
chemical_list: D007328:Insulin; D020738:Leptin; D011333:Pro-Opiomelanocortin; D054562:Protein Tyrosine Phosphatase, Non-Receptor Type 1; D054578:Protein Tyrosine Phosphatase, Non-Receptor Type 2; C516609:Ptpn1 protein, mouse