title: Leptin signaling regulates glucose homeostasis, but not adipostasis, in the zebrafish.
abstract: Leptin is the primary adipostatic factor in mammals. Produced largely by adipocytes in proportion to total adipose mass, the hormone informs the brain regarding total energy stored as triglycerides in fat cells. The hormone acts on multiple circuits in the brain to regulate food intake, autonomic outflow, and endocrine function to maintain energy balance. In addition to regulating adipose mass, mammalian leptin also plays a role in the regulation of glucose homeostasis and as a gating factor in reproductive competence. Leptin-deficient mice and people exhibit early onset profound hyperphagia and obesity, diabetes, and infertility. Although leptin and the leptin receptor are found in fish, the hormone is not expressed in adipose tissue, but is found in liver and other tissues. Here, we show that adult zebrafish lacking a functional leptin receptor do not exhibit hyperphagia or increased adiposity, and exhibit normal fertility. However, leptin receptor-deficient larvae have increased numbers of β-cells and increased levels of insulin mRNA. Furthermore, larval zebrafish have been shown to exhibit β-cell hyperplasia in response to high fat feeding or peripheral insulin resistance, and we show here that leptin receptor is required for this response. Adult zebrafish also have increased levels of insulin mRNA and other alterations in glucose homeostasis. Thus, a role for leptin in the regulation of β-cell mass and glucose homeostasis appears to be conserved across vertebrates, whereas its role as an adipostatic factor is likely to be a secondary role acquired during the evolution of mammals.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: Maximilian
authors.initials: M
authors.lastname: Michel
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: Patrick S
authors.initials: PS
authors.lastname: Page-McCaw
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232.
authors.forename: Wenbiao
authors.initials: W
authors.lastname: Chen
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232 roger.cone@vanderbilt.edu.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
mesh_terms: D050154:Adiposity / Q000502:physiology*; D000595:Amino Acid Sequence; D000818:Animals; D049628:Body Size; D001835:Body Weight; D002452:Cell Count; D064112:Clustered Regularly Interspaced Short Palindromic Repeats; D004041:Dietary Fats; D005298:Fertility; D005947:Glucose / Q000378:metabolism*; D005951:Glucose Tolerance Test; D050261:Glycogenolysis; D006019:Glycolysis; D006706:Homeostasis; D006963:Hyperphagia / Q000235:genetics / Q000503:physiopathology; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000502:physiology*; D007814:Larva; D020738:Leptin / Q000235:genetics / Q000502:physiology*; D008099:Liver / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010641:Phenotype; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D054411:Receptors, Leptin / Q000235:genetics / Q000502:physiology*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000502:physiology; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development / Q000502:physiology; D029961:Zebrafish Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D004041:Dietary Fats; D007328:Insulin; D020738:Leptin; D012333:RNA, Messenger; D054411:Receptors, Leptin; D029961:Zebrafish Proteins; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose
keywords: adipostasis; glucose homeostasis; leptin; zebrafish