Attenuation of High-fat Diet-induced Weight Gain by Apolipoprotein A4

Overview

Journal Obesity (Silver Spring)

Specialties Endocrinology
Nutritional Sciences
Physiology

Date 2024 Nov 14

PMID 39540259

Authors

Hsuan-Chih N Kuo

Zachary LaRussa

Flora Mengyang Xu

Leslie A Consitt

Min Liu

W Sean Davidson

Vishwajeet Puri

Karen T Coschigano

Haifei Shi

Chunmin C Lo

Affiliations

Soon will be listed here.

Abstract

Objective: Apolipoprotein A4 (APOA4) is synthesized by the small intestine in response to dietary lipids. Chronic exposure to a high-fat diet (HFD) desensitizes lipid-induced APOA4 production and attenuates brown adipose tissue (BAT) thermogenesis. We hypothesized that exogenous APOA4 could increase BAT thermogenesis and energy expenditure in HFD-fed mice, resulting in decreased obesity and improved glucose tolerance.

Methods: BAT and inguinal white adipose tissue (IWAT) thermogenesis, body composition, energy intake and expenditure, and locomotor activity were measured using an infrared camera, immunoblots, quantitative magnetic resonance imaging, and a comprehensive lab animal monitoring system. An intraperitoneal glucose tolerance test and hepatic lipid accumulation and steatosis were assayed.

Results: Mice receiving continuous infusion of APOA4 for the last 4 weeks of 10 weeks of HFD feeding gained no additional body weight and had reduced fat mass but enhanced BAT and IWAT thermogenesis and energy expenditure, despite unaltered food intake and locomotor activity. Additionally, APOA4 infusion elevated fatty acid β oxidation; decreased lipogenesis, lipid accumulation, and steatosis in liver; and improved glucose tolerance.

Conclusions: Maintenance of plasma APOA4 via exogenous APOA4 protein parallels elevation of BAT and IWAT thermogenesis, hepatic fatty acid β oxidation, and overall energy expenditure, with subsequent prevention of additional weight gain in HFD-fed obese mice.

Citing Articles

Attenuation of high-fat diet-induced weight gain by apolipoprotein A4.

Kuo H, LaRussa Z, Xu F, Consitt L, Liu M, Davidson W Obesity (Silver Spring). 2024; 32(12):2321-2333.

PMID: 39540259 PMC: 11589529. DOI: 10.1002/oby.24155.

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