Parathyroid hormone-related protein prevents high-fat-diet-induced obesity, hepatic steatosis and insulin resistance in mice

Obesity, closely related to systematic metabolic disorders, has become a major public health problem in recent decades. Here, we aimed to study the function of Parathyroid hormone-related protein (PTHrP) on high fat diet (HFD) induced murine obesity. Male C57BL/6J mice were transduced with adeno-ass...

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Published in:ENDOCRINE JOURNAL 2022, Vol.69(1), pp.55-65
Main Authors: Qin, Biyan, Qincao, Litao, He, Shuying, Liao, Yan, Shi, Jie, Xie, Fang, Diao, Na, Bai, Lan
Format: Article
Language:English
Subjects:
Adipose tissue
Adipose tissue (brown)
Body fat
Body weight
Dyslipidemia
Fatty liver
Hepatic steatosis
High fat diet
High protein diet
Homeostasis
Hypertrophy
Inflammation
Insulin
Insulin resistance
Metabolic disorders
Metabolism
Obesity
Parathyroid
Parathyroid hormone
Parathyroid hormone-related protein
Parathyroid hormone-related protein (PTHrP)
Protein kinase A
Proteins
Public health
Signal transduction
Steatosis
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Summary:Obesity, closely related to systematic metabolic disorders, has become a major public health problem in recent decades. Here, we aimed to study the function of Parathyroid hormone-related protein (PTHrP) on high fat diet (HFD) induced murine obesity. Male C57BL/6J mice were transduced with adeno-associated virus vector encoding PTHrP (AAV-PTHrP) or adeno-associated virus control vector (AAV-Vehicle), following with HFD for 8 weeks. In addition, mice without transduction were fed on normal diet or HFD, respectively. Histological, metabolic and biochemical changes were detected. At the endpoint of experiment, body weight of mice treated with AAV-PTHrP did not increase as much as mice with AAV-Vehicle, but similar as mice with normal diet. Food efficiency ratio and weight of interscapular brown adipose tissue and epididymal white adipose tissue in mice overexpressed PTHrP were also lower than mice transducted with AAV-Vehicle. Besides, administration of AAV-PTHrP inhibited HFD-induced adipocyte hypertrophy. Protein level of PKA signaling pathway and thermogenic gene in adipose tissue exhibited a significant raise in HFD + AAV-PTHrP group, whereas transcription of inflammatory gene were decreased. Additionally, PTHrP overexpression ameliorated HFD-induced dyslipidemia, hepatic steatosis and insulin sensitivity. In HFD-induced murine obesity model, PTHrP is crucial to maintain metabolic homeostasis. PTHrP drives white adipose tissue browning and inhibits whitening of brown adipose tissue. Most importantly, PTHrP prevented HFD-induced obesity, hepatic steatosis and insulin resistance.
ISSN:0918-8959
1348-4540
DOI:10.1507/endocrj.EJ20-0728