title: Asprosin, a Fasting-Induced Glucogenic Protein Hormone.
abstract: Hepatic glucose release into the circulation is vital for brain function and survival during periods of fasting and is modulated by an array of hormones that precisely regulate plasma glucose levels. We have identified a fasting-induced protein hormone that modulates hepatic glucose release. It is the C-terminal cleavage product of profibrillin, and we name it Asprosin. Asprosin is secreted by white adipose, circulates at nanomolar levels, and is recruited to the liver, where it activates the G protein-cAMP-PKA pathway, resulting in rapid glucose release into the circulation. Humans and mice with insulin resistance show pathologically elevated plasma asprosin, and its loss of function via immunologic or genetic means has a profound glucose- and insulin-lowering effect secondary to reduced hepatic glucose release. Asprosin represents a glucogenic protein hormone, and therapeutically targeting it may be beneficial in type II diabetes and metabolic syndrome.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Chase
authors.initials: C
authors.lastname: Romere
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Clemens
authors.initials: C
authors.lastname: Duerrschmid
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Juan
authors.initials: J
authors.lastname: Bournat
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Petra
authors.initials: P
authors.lastname: Constable
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Mahim
authors.initials: M
authors.lastname: Jain
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Fan
authors.initials: F
authors.lastname: Xia
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Pradip K
authors.initials: PK
authors.lastname: Saha
authors.affiliation: Department of Pharmacology and Systems Therapeutics, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
authors.forename: Maria
authors.initials: M
authors.lastname: Del Solar
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Bokai
authors.initials: B
authors.lastname: Zhu
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Brian
authors.initials: B
authors.lastname: York
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Poonam
authors.initials: P
authors.lastname: Sarkar
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Rendon
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: M Waleed
authors.initials: MW
authors.lastname: Gaber
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Scott A
authors.initials: SA
authors.lastname: LeMaire
authors.affiliation: Division of Cardiothoracic Surgery, Michael E. DeBakey Department of Surgery, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Joseph S
authors.initials: JS
authors.lastname: Coselli
authors.affiliation: Department of Internal Medicine, University of Texas Medical School at Houston, Houston, TX 77030, USA.
authors.forename: Dianna M
authors.initials: DM
authors.lastname: Milewicz
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: V Reid
authors.initials: VR
authors.lastname: Sutton
authors.affiliation: Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Nancy F
authors.initials: NF
authors.lastname: Butte
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: David D
authors.initials: DD
authors.lastname: Moore
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030, USA. Electronic address: chopra@bcm.edu.
authors.forename: Atul R
authors.initials: AR
authors.lastname: Chopra
mesh_terms: D052436:Adipose Tissue, White / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D000906:Antibodies / Q000008:administration & dosage; D002940:Circadian Rhythm; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D005215:Fasting / Q000097:blood / Q000378:metabolism*; D005260:Female; D005317:Fetal Growth Retardation / Q000378:metabolism; D000071838:Fibrillin-1; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008840:Microfilament Proteins / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D036361:Peptide Hormones / Q000097:blood / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011371:Progeria / Q000378:metabolism; D011994:Recombinant Proteins / Q000008:administration & dosage; D016415:Sequence Alignment; D054392:Adipokines
chemical_list: D000906:Antibodies; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000071838:Fibrillin-1; D005947:Glucose; D007328:Insulin; D008840:Microfilament Proteins; D010446:Peptide Fragments; D036361:Peptide Hormones; D011994:Recombinant Proteins; C000605722:FBN1 protein, human; D054392:Adipokines