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Novel Regulators of Feeding and Cardiovascular Physiology in Fish

dc.contributor.advisorUnniappan, Suraj
dc.contributor.committeeMemberMacPhee, Daniel
dc.contributor.committeeMemberWeber , Lynn
dc.contributor.committeeMemberFerrari , Maud
dc.contributor.committeeMemberHogan , Natacha
dc.creatorSundarrajan, Lakshminarasimhan 1989-
dc.date.accessioned2018-05-22T15:33:31Z
dc.date.available2019-05-22T06:05:08Z
dc.date.created2018-05
dc.date.issued2018-05-22
dc.date.submittedMay 2018
dc.date.updated2018-05-22T15:33:31Z
dc.description.abstractNesfatin-1, an 82 amino acid anorexigen is encoded in a secreted precursor, nucleobindin-2 (NUCB2). NUCB2 was named so due to its high sequence similarity with nucleobindin-1 (NUCB1). It was recently reported that NUCB1 encodes an insulinotropic nesfatin-1-like peptide (NLP) in mice. Irisin, a muscle protein is encoded in its precursor fibronectin type III domain containing 5 (FNDC5) and released into blood from skeletal muscle. Here we aimed to characterize NLP and irisin in fish, and to study whether these are novel regulators of feeding and cardiovascular functions in zebrafish and goldfish. Western blot analysis and immunohistochemical studies determined the expression of NUCB1/NLP in central and peripheral tissues of goldfish. Administration of rat and goldfish NLP at 10 and 100 ng/g body weight doses caused potent inhibition of food intake in goldfish. NLP also downregulated the expression of preproghrelin and orexin-A mRNA, and upregulated cocaine and amphetamine regulated transcript (CART) mRNA in goldfish brain. Intraperitoneal (I.P) administration of NLP reduced cardiac functions in zebrafish and goldfish, downregulated irisin, and RyR1b mRNA expression in zebrafish. Irisin was detected in zebrafish heart and skeletal muscle. Single I.P. injection of irisin did not affect feeding, but its knockdown using siRNA caused a significant reduction in food intake. Knockdown of irisin reduced ghrelin and orexin-A mRNA expression, and increased CART mRNA expression in zebrafish brain and gut. Meanwhile, injection of irisin (0.1 and 1 ng/g B.W) increased cardiac functions, while knockdown of irisin resulted in reverse effects on cardiovascular physiology. Administration of propranolol attenuated the effects of irisin on cardiac physiology. Collectively, my research discovered that NLP and irisin modulate food intake and cardiac physiology in fish. Future studies should focus on the mechanisms of action of NLP and irisin in regulating metabolism and cardiovascular biology in fish.
dc.format.mimetypeapplication/pdf
dc.identifier.urihttp://hdl.handle.net/10388/8583
dc.subjectNesfatin-1-Like Peptide
dc.subjectIrisin
dc.subjectFeeding
dc.subjectCardiovascular Physiology
dc.titleNovel Regulators of Feeding and Cardiovascular Physiology in Fish
dc.typeThesis
dc.type.materialtext
local.embargo.terms2019-05-22
thesis.degree.departmentWestern College of Veterinary Medicine
thesis.degree.disciplineVeterinary Biomedical Sciences
thesis.degree.grantorUniversity of Saskatchewan
thesis.degree.levelDoctoral
thesis.degree.nameDoctor of Philosophy (Ph.D.)

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