The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution

Li Zhao, Chunfang Zhu, Meng Lu, Chi Chen, Xiaomin Nie, Buatikamu Abudukerimu, Kun Zhang, Zhiyuan Ning, Yi Chen, Jing Cheng, Fangzhen Xia, Ningjian Wang, Michael Dennis Jensen, Yingli Lu

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are an ideal therapy for type 2 diabetes and, as of recently, for obesity. In contrast to visceral fat, subcutaneous fat appears to be protective against metabolic diseases. Here, we aimed to explore whether liraglutide, a GLP-1RA, could redistribute body fat via regulating lipid metabolism in different fat depots. After being fed a high-fat diet for 8 weeks, 50 male Wistar and Goto-Kakizaki rats were randomly divided into a normal control group, a diabetic control group, low- and high-dose liraglutide-treated groups and a diet-control group. Different doses of liraglutide (400 μg/kg/day or 1200 μg/kg/day) or an equal volume of normal saline were administered to the rats subcutaneously once a day for 12 weeks. Body composition and body fat deposition were measured by dual-energy X-ray absorptiometry and MRI. Isotope tracers were infused to explore lipid metabolism in different fat depots. Quantitative real-time PCR and Western blot analyses were conducted to evaluate the expression of adipose-related genes. The results showed that liraglutide decreased visceral fat and relatively increased subcutaneous fat. Lipogenesis was reduced in visceral white adipose tissue (WAT) but was elevated in subcutaneous WAT. Lipolysis was also attenuated, and fatty acid oxidation was enhanced. The mRNA expression levels of adipose-related genes in different tissues displayed similar trends after liraglutide treatment. In addition, the expression of browning-related genes was upregulated in subcutaneous WAT. Taken together, the results suggested that liraglutide potentially redistributes body fat and promotes browning remodeling in subcutaneous WAT to improve metabolic disorders.

Original languageEnglish (US)
Pages (from-to)271-286
Number of pages16
JournalJournal of Endocrinology
Volume240
Issue number2
DOIs
StatePublished - Feb 1 2019

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Subcutaneous Fat
Adipose Tissue
White Adipose Tissue
Intra-Abdominal Fat
Lipid Metabolism
Control Groups
Fats
Genes
Lipogenesis
Lipolysis
Metabolic Diseases
Photon Absorptiometry
High Fat Diet
Body Composition
Isotopes
Type 2 Diabetes Mellitus
Glucagon-Like Peptide-1 Receptor
Liraglutide
Real-Time Polymerase Chain Reaction
Fatty Acids

Keywords

  • Glucagon-like peptide-1
  • Isotope tracer
  • Lipid metabolism diabetes
  • Liraglutide

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Endocrinology

Cite this

Zhao, L., Zhu, C., Lu, M., Chen, C., Nie, X., Abudukerimu, B., ... Lu, Y. (2019). The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution. Journal of Endocrinology, 240(2), 271-286. https://doi.org/10.1530/JOE-18-0374

The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution. / Zhao, Li; Zhu, Chunfang; Lu, Meng; Chen, Chi; Nie, Xiaomin; Abudukerimu, Buatikamu; Zhang, Kun; Ning, Zhiyuan; Chen, Yi; Cheng, Jing; Xia, Fangzhen; Wang, Ningjian; Jensen, Michael Dennis; Lu, Yingli.

In: Journal of Endocrinology, Vol. 240, No. 2, 01.02.2019, p. 271-286.

Research output: Contribution to journalArticle

Zhao, L, Zhu, C, Lu, M, Chen, C, Nie, X, Abudukerimu, B, Zhang, K, Ning, Z, Chen, Y, Cheng, J, Xia, F, Wang, N, Jensen, MD & Lu, Y 2019, 'The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution', Journal of Endocrinology, vol. 240, no. 2, pp. 271-286. https://doi.org/10.1530/JOE-18-0374
Zhao, Li ; Zhu, Chunfang ; Lu, Meng ; Chen, Chi ; Nie, Xiaomin ; Abudukerimu, Buatikamu ; Zhang, Kun ; Ning, Zhiyuan ; Chen, Yi ; Cheng, Jing ; Xia, Fangzhen ; Wang, Ningjian ; Jensen, Michael Dennis ; Lu, Yingli. / The key role of a glucagon-like peptide-1 receptor agonist in body fat redistribution. In: Journal of Endocrinology. 2019 ; Vol. 240, No. 2. pp. 271-286.
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