1646-P: Apolipoprotein A4 Improves Glucose Homeostasis through Activation of BAT Thermogenesis in Obese Mice

1646-P: Apolipoprotein A4 Improves Glucose Homeostasis through Activation of BAT Thermogenesis in Obese Mice

Obesity is associated with impaired insulin sensitivity and the development of type 2 diabetes. Activation of brown adipose tissue (BAT) thermogenesis enhances triglyceride clearance and insulin sensitivity. Apolipoprotein A4 (ApoA4) induced by dietary lipids elevates BAT thermogenesis in lean mice....

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Bibliographic Details
Published in:Diabetes (New York, N.Y.) Vol. 73; p. 1
Main Authors: Larussa, Zachary D, Kuo, Hsuanchih, Baumgarte, Jace, Shi, Haifei, Lo, Chunmin C
Format: Journal Article
Language:English
Published: New York American Diabetes Association 01-06-2024
Subjects:
Adipose tissue (brown)
Apolipoproteins
Body weight gain
Diabetes mellitus (non-insulin dependent)
Elevated temperature test
Fatty liver
Glucose
Glucose tolerance
High fat diet
Homeostasis
Insulin
Lipids
Obesity
Small intestine
Steatosis
Temperature tolerance
Thermogenesis
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Summary:Obesity is associated with impaired insulin sensitivity and the development of type 2 diabetes. Activation of brown adipose tissue (BAT) thermogenesis enhances triglyceride clearance and insulin sensitivity. Apolipoprotein A4 (ApoA4) induced by dietary lipids elevates BAT thermogenesis in lean mice. Chronic consumption of high-fat diet (HFD) attenuates APOA4 production in small intestine and BAT thermogenesis. The hypothesis of this study was that the continuous infusion of mouse ApoA4 protein would increase BAT thermogenesis and improve glucose homeostasis in HFD-induced obese mice. Male mice were maintained on an HFD (60% kcals fat) for 10 weeks, during the last 4 weeks, mice received a pump infusion of vehicle or ApoA4 at a physiological dose (1.2 mg ApoA4/kg body weight). Glucose tolerance test, BAT thermogenesis, lipid accumulation in liver, and body weight were measured in mice with ApoA4 or vehicle treatment. Serum glucose and plasma insulin in ApoA4-treated mice was lower than in saline-treated mice following a glucose challenge. BAT temperature and thermogenesis were elevated in ApoA4-treated mice compared to saline-treated mice. Further, ApoA4-treated mice had increased fatty acid oxidation, reduced lipid content, and attenuated steatosis in the liver and decreased body weight gain relative to the saline control mice.
ISSN:0012-1797
1939-327X
DOI:10.2337/db24-1646-P