title: Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis.
abstract: Angiopoietin-like protein (ANGPTL)8 (alternatively called TD26, RIFL, Lipasin, and Betatrophin) is a newly recognized ANGPTL family member that has been implicated in both triglyceride (TG) and glucose metabolism. Hepatic overexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactivating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8(-/-)) mice gained weight more slowly than wild-type littermates due to a selective reduction in adipose tissue accretion. Plasma levels of TGs of the Angptl8(-/-) mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG levels were associated with both a reduction in very low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) activity. Despite the increase in LPL activity, the uptake of very low density lipoprotein-TG is markedly reduced in adipose tissue but preserved in hearts of fed Angptl8(-/-) mice. Taken together, these data indicate that ANGPTL8 plays a key role in the metabolic transition between fasting and refeeding; it is required to direct fatty acids to adipose tissue for storage in the fed state. Finally, glucose and insulin tolerance testing revealed no alterations in glucose homeostasis in mice fed either a chow or high fat diet. Thus, although absence of ANGPTL8 profoundly disrupts TG metabolism, we found no evidence that it is required for maintenance of glucose homeostasis.
authors.affiliation: Howard Hughes Medical Institute and Departments of Molecular Genetics and Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.forename: Fabiana
authors.initials: F
authors.lastname: Quagliarini
authors.forename: Viktoria
authors.initials: V
authors.lastname: Gusarova
authors.forename: Jesper
authors.initials: J
authors.lastname: Gromada
authors.forename: David M
authors.initials: DM
authors.lastname: Valenzuela
authors.forename: Jonathan C
authors.initials: JC
authors.lastname: Cohen
authors.forename: Helen H
authors.initials: HH
authors.lastname: Hobbs
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D000818:Animals; D001692:Biological Transport / Q000502:physiology; D002153:Calorimetry, Indirect; D015243:Cholesterol, VLDL / Q000097:blood; D050171:Dyslipidemias / Q000188:drug therapy / Q000378:metabolism*; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis / Q000502:physiology*; D015151:Immunoblotting; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D036361:Peptide Hormones / Q000172:deficiency* / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D014280:Triglycerides / Q000097:blood / Q000378:metabolism*
chemical_list: C000595899:ANGPTL8 protein, mouse; D000091306:Angiopoietin-Like Protein 8; D000075802:Angiopoietin-like Proteins; D015243:Cholesterol, VLDL; D036361:Peptide Hormones; D014280:Triglycerides; D005947:Glucose
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