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Open Access 01-12-2019 | Obesity | Research

Gdf11 gene transfer prevents high fat diet-induced obesity and improves metabolic homeostasis in obese and STZ-induced diabetic mice

Authors: Bingxin Lu, Jianing Zhong, Jianfei Pan, Xiaopeng Yuan, Mingzhi Ren, Liping Jiang, Yuqing Yang, Guisheng Zhang, Dexi Liu, Chunbo Zhang

Published in: Journal of Translational Medicine | Issue 1/2019

Abstract

Background

The growth differentiation factor 11 (GDF11) was shown to reverse age-related hypertrophy on cardiomyocytes and considered as anti-aging rejuvenation factor. The role of GDF11 in regulating metabolic homeostasis is unclear. In this study, we investigated the functions of GDF11 in regulating metabolic homeostasis and energy balance.

Methods

Using a hydrodynamic injection approach, plasmids carrying a mouse Gdf11 gene were delivered into mice and generated the sustained Gdf11 expression in the liver and its protein level in the blood. High fat diet (HFD)-induced obesity was employed to examine the impacts of Gdf11 gene transfer on HFD-induced adiposity, hyperglycemia, insulin resistance, and hepatic lipid accumulation. The impacts of GDF11 on metabolic homeostasis of obese and diabetic mice were examined using HFD-induced obese and STZ-induced diabetic models.

Results

Gdf11 gene transfer alleviates HFD-induced obesity, hyperglycemia, insulin resistance, and fatty liver development. In obese and STZ-induced diabetic mice, Gdf11 gene transfer restores glucose metabolism and improves insulin resistance. Mechanism study reveals that Gdf11 gene transfer increases the energy expenditure of mice, upregulates the expression of genes responsible for thermoregulation in brown adipose tissue, downregulates the expression of inflammatory genes in white adipose tissue and those involved in hepatic lipid and glucose metabolism. Overexpression of GDF11 also activates TGF-β/Smad2, PI3K/AKT/FoxO1, and AMPK signaling pathways in white adipose tissue.

Conclusions

These results demonstrate that GDF11 plays an important role in regulating metabolic homeostasis and energy balance and could be a target for pharmacological intervention to treat metabolic disease.

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Title: Gdf11 gene transfer prevents high fat diet-induced obesity and improves metabolic homeostasis in obese and STZ-induced diabetic mice
Authors: Bingxin Lu
Jianing Zhong
Jianfei Pan
Xiaopeng Yuan
Mingzhi Ren
Liping Jiang
Yuqing Yang
Guisheng Zhang
Dexi Liu
Chunbo Zhang
Publication date: 01-12-2019
Publisher: BioMed Central
Keywords: Obesity
Obesity
Insulins
Fatty Liver
Glucose Tolerance Test
Insulins
Published in: Journal of Translational Medicine / Issue 1/2019
Electronic ISSN: 1479-5876
DOI: https://doi.org/10.1186/s12967-019-02166-1

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