RGD Reference Report - CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats. - Rat Genome Database

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CRISPR/Cas9-mediated Angptl8 knockout suppresses plasma triglyceride concentrations and adiposity in rats.

Authors: Izumi, Ryota  Kusakabe, Toru  Noguchi, Michio  Iwakura, Hiroshi  Tanaka, Tomohiro  Miyazawa, Takashi  Aotani, Daisuke  Hosoda, Kiminori  Kangawa, Kenji  Nakao, Kazuwa 
Citation: Izumi R, etal., J Lipid Res. 2018 Sep;59(9):1575-1585. doi: 10.1194/jlr.M082099. Epub 2018 Jul 24.
RGD ID: 38549347
Pubmed: PMID:30042156   (View Abstract at PubMed)
PMCID: PMC6121927   (View Article at PubMed Central)
DOI: DOI:10.1194/jlr.M082099   (Journal Full-text)

Angiopoietin-like protein (ANGPTL)8 is a liver- and adipocyte-derived protein that controls plasma triglyceride (TG) levels. Most animal studies have used mouse models. Here, we generated an Angptl8 KO rat model using a clustered regulatory interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein 9 (Cas9) (CRISPR/Cas9) system to clarify the roles of ANGPTL8 in glucose and lipid metabolism. Compared with WT rats, Angptl8 KO rats had lower body weight and fat content, associated with impaired lipogenesis in adipocytes; no differences existed between the groups in food intake or rectal temperature. Plasma TG levels in both the fasted and refed states were significantly lower in KO than in WT rats, and an oral fat tolerance test showed decreased plasma TG excursion in Angptl8 KO rats. Higher levels of lipase activity in the heart and greater expression of genes related to β-oxidation in heart and skeletal muscle were observed in Angptl8 KO rats. However, there were no significant differences between KO and WT rats in glucose metabolism or the histology of pancreatic β-cells on both standard and high-fat diets. In conclusion, we demonstrated that Angptl8 KO in rats resulted in lower body weight and plasma TG levels without affecting glucose metabolism. ANGPTL8 might be an important therapeutic target for obesity and dyslipidemia.

Objects Annotated

Genes (Rattus norvegicus)
Angptl8  (angiopoietin-like 8)
Angptl8em1Kyo  (angiopoietin-like 8; CRISPR/Cas9 induced mutant 1, Kyo)

Objects referenced in this article
Strain F344-Angptl8em2Kyo+/- null Rattus norvegicus
Strain F344-Angptl8em2Kyo-/- null Rattus norvegicus

Additional Information