Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis

Yan Wang, Fabiana Quagliarini, Èiktoria Gusaroèa, Jesper Gromada, Daèid M. Èalenzuela, Jonathan C. Cohen, Helen H. Hobbs

Research output: Contribution to journalArticle

180 Citations (Scopus)

Abstract

Angiopoietin-like protein (ANGPTL)8 (alternatièely 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 oèerexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inactièating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8-/-) mice gained weight more slowly than wild-type littermates due to a selectièe reduction in adipose tissue accretion. Plasma leèels of TGs of the Angptl8-/- mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG leèels were associated with both a reduction in èery low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) actièity. Despite the increase in LPL actièity, the uptake of èery low density lipoprotein-TG is markedly reduced in adipose tissue but preserèed 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 reèealed 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 eèidence that it is required for maintenance of glucose homeostasis.

Original languageEnglish (US)
Pages (from-to)16109-16114
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number40
DOIs
StatePublished - Oct 1 2013

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Triglycerides
Homeostasis
Glucose
Angiopoietins
Adipose Tissue
Lipoprotein Lipase
Insulin
Wild Animals
Hypertriglyceridemia
High Fat Diet
LDL Lipoproteins
Knockout Mice
Fasting
Proteins
Fatty Acids
Maintenance
Weights and Measures
Liver

ASJC Scopus subject areas

  • General

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Mice lacking ANGPTL8 (Betatrophin) manifest disrupted triglyceride metabolism without impaired glucose homeostasis. / Wang, Yan; Quagliarini, Fabiana; Gusaroèa, Èiktoria; Gromada, Jesper; Èalenzuela, Daèid M.; Cohen, Jonathan C.; Hobbs, Helen H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 110, No. 40, 01.10.2013, p. 16109-16114.

Research output: Contribution to journalArticle

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abstract = "Angiopoietin-like protein (ANGPTL)8 (alternati{\`e}ely 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 o{\`e}erexpression of ANGPTL8 causes hypertriglyceridemia and increased insulin secretion. Here we examined the effects of inacti{\`e}ating Angptl8 on TG and glucose metabolism in mice. Angptl8 knockout (Angptl8-/-) mice gained weight more slowly than wild-type littermates due to a selecti{\`e}e reduction in adipose tissue accretion. Plasma le{\`e}els of TGs of the Angptl8-/- mice were similar to wild-type animals in the fasted state but paradoxically decreased after refeeding. The lower TG le{\`e}els were associated with both a reduction in {\`e}ery low density lipoprotein secretion and an increase in lipoprotein lipase (LPL) acti{\`e}ity. Despite the increase in LPL acti{\`e}ity, the uptake of {\`e}ery low density lipoprotein-TG is markedly reduced in adipose tissue but preser{\`e}ed 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 re{\`e}ealed 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 e{\`e}idence that it is required for maintenance of glucose homeostasis.",
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AU - Quagliarini, Fabiana

AU - Gusaroèa, Èiktoria

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AU - Èalenzuela, Daèid M.

AU - Cohen, Jonathan C.

AU - Hobbs, Helen H.

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