2. Academic Validation
  3. GDF15 is a major determinant of ketogenic diet-induced weight loss

GDF15 is a major determinant of ketogenic diet-induced weight loss

  • Cell Metab. 2023 Dec 5;35(12):2165-2182.e7. doi: 10.1016/j.cmet.2023.11.003.
Jun Feng Lu 1,  Meng Qing Zhu 1,  Bo Xia 1,  Na Na Zhang 2,  Xiao Peng Liu 1,  Huan Liu 1,  Rui Xin Zhang 1,  Jun Ying Xiao 1,  Hui Yang 3,  Ying Qi Zhang 4,  Xiao Miao Li 5,  Jiang Wei Wu 6
Affiliations

Affiliations

  • 1 Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China.
  • 2 Department of Endocrinology and Metabolism, First Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi 710032, China.
  • 3 National Health Commission (NHC) Key Laboratory of Food Safety Risk Assessment, China National Center for Food Safety Risk Assessment, Beijing 100022, China.
  • 4 State Key Laboratory of Cancer Biology, Biotechnology Center, School of Pharmacy, Air Force Medical University, Xi'an, Shaanxi 710032, China.
  • 5 Department of Endocrinology and Metabolism, First Affiliated Hospital of Air Force Medical University, Xi'an, Shaanxi 710032, China. Electronic address: xiaomiao@fmmu.edu.cn.
  • 6 Key Laboratory of Animal Genetics, Breeding and Reproduction of Shaanxi Province, College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, China. Electronic address: wujiangwei@nwafu.edu.cn.
PMID: 38056430 DOI: 10.1016/j.cmet.2023.11.003
Abstract

A ketogenic diet (KD) has been promoted as an obesity management diet, yet its underlying mechanism remains elusive. Here we show that KD reduces energy intake and body weight in humans, pigs, and mice, accompanied by elevated circulating Growth Differentiation Factor 15 (GDF15). In GDF15- or its receptor GFRAL-deficient mice, these effects of KD disappeared, demonstrating an essential role of GDF15-GFRAL signaling in KD-mediated weight loss. Gdf15 mRNA level increases in hepatocytes upon KD feeding, and knockdown of Gdf15 by AAV8 abrogated the obesity management effect of KD in mice, corroborating a hepatic origin of GDF15 production. We show that KD activates hepatic PPARγ, which directly binds to the regulatory region of Gdf15, increasing its transcription and production. Hepatic Pparγ-knockout mice show low levels of plasma GDF15 and significantly diminished obesity management effects of KD, which could be restored by either hepatic Gdf15 overexpression or recombinant GDF15 administration. Collectively, our study reveals a previously unexplored GDF15-dependent mechanism underlying KD-mediated obesity management.

Keywords

GDF15; GFRAL; hepatic PPARγ; ketogenic diet; obesity.

Figures
Products
嗨！很高兴为您提供帮助！

尊敬的 MCE 客户您好，
请您选择所在区域，我们将转接对应客服为您服务！

热门区域

A

B

C

F

G

H

J

L

N

Q

S

T

X

Y

Z

热 A B C F G H J L N Q S T X Y Z