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Novel Regulators of Feeding and Cardiovascular Physiology in Fish

Date

2018-05-22

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Thesis

Degree Level

Doctoral

Abstract

Nesfatin-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.

Description

Keywords

Nesfatin-1-Like Peptide, Irisin, Feeding, Cardiovascular Physiology

Citation

Degree

Doctor of Philosophy (Ph.D.)

Department

Western College of Veterinary Medicine

Program

Veterinary Biomedical Sciences

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