RGD Reference Report - Apolipoprotein A-IV involves in glucose and lipid metabolism of rat. - Rat Genome Database

RGD Reference Report - Apolipoprotein A-IV involves in glucose and lipid metabolism of rat. - Rat Genome Database

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Apolipoprotein A-IV involves in glucose and lipid metabolism of rat.
Authors:	Wang, Zhenguo Wang, Lu Zhang, Zhuzhen Feng, Li Song, Xue Wu, Jiarui
Citation:	Wang Z, etal., Nutr Metab (Lond). 2019 Jul 2;16:41. doi: 10.1186/s12986-019-0367-2. eCollection 2019.
RGD ID:	150429948
Pubmed:	PMID:31303888 (View Abstract at PubMed)
PMCID:	PMC6604154 (View Article at PubMed Central)
DOI:	DOI:10.1186/s12986-019-0367-2 (Journal Full-text)
Background: Apolipoprotein A-IV (ApoA-IV) exists in relatively high levels in the circulation systems of animals, but its roles are not fully elucidated. It is known that the Apoa4 gene resides in the cluster Apoa1/Apoc3/Apoa4. Because of a short intergenic sequence between Apoc3 and Apoa4, a previous ApoA-IV knockout mouse model by gene targeting had an accompanying deficiency in ApoC-III expression, which limited its application in investigating the precise roles of ApoA-IV. To solve this problem, we created a specific knockout of ApoA-IV in Sprague-Dawlay rats by TALEN approach. Methods: Age-matched knockout rats and their wild-type littermate controls maintained on a standard rodent diet were studied and blood metabolic parameters were measured. Glucose, insulin, olive oil, and intralipid tolerance tests were performed to study the glucose and lipid metabolism of rats. Quantitative real-time PCR and RNA-seq analysis in liver and inguinal white adipose tissue (iWAT) of rats at three ages (18 weeks, 45 weeks and 90 weeks) were performed to identify the genes altered by ApoA-IV knockout. Results: ApoA-IV knockout rats were apparently normal and fertile, but exhibited improved glucose clearance when challenged with glucose tolerance test. In addition, fasting-induced hepatic steatosis was more pronounced in ApoA-IV knockout rats. Further analysis identified that a set of hepatic genes involved in glycolysis, gluconeogenesis and de novo lipogenesis were altered in the absence of ApoA-IV, which induced enhanced glycolysis, attenuated gluconeogenesis and elevated de novo lipogenesis. And the RNA-seq results also confirmed that almost all the genes mentioned in the phenotyping section were highly consistent throughout the three studied ages. Conclusions: ApoA-IV functions in an age-independent manner in the modulation of glucose and lipid metabolism of rats, and may serve as a potential linker between hepatic glucose and lipid metabolism.

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Mammalian Phenotype

Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Apoa4	Rat	decreased circulating glucose level	induces	IMP	XCO:0000275,XCO:0000102	compared to wild type	RGD
Apoa4^em1Bcgen	Rat	decreased circulating glucose level	induces	IMP	XCO:0000275,XCO:0000102	compared to wild type	RGD
SD-Apoa4^em1Bcgen	Rat	decreased circulating glucose level	induces	IMP	glucose and fasting	compared to wild type	RGD
Apoa4	Rat	hepatic steatosis	induces	IMP	XCO:0000102	compared to wild type	RGD
Apoa4^em1Bcgen	Rat	hepatic steatosis	induces	IMP	XCO:0000102	compared to wild type	RGD
SD-Apoa4^em1Bcgen	Rat	hepatic steatosis	induces	IMP	fasting	compared to wild type	RGD

Objects Annotated

Genes (Rattus norvegicus)

Apoa4 (apolipoprotein A4)

Apoa4^em1Bcgen (apolipoprotein A4; TALEN induced mutant 1, Bcgn)

Strains

SD-Apoa4^em1Bcgen (NA)

Additional Information