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EBioMedicine. 2019 Feb;40:56-66. doi: 10.1016/j.ebiom.2018.11.057. Epub 2018 Dec 7.

The browning of white adipose tissue and body weight loss in primary hyperparathyroidism.

Author information

1
Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China.
2
Department of Nuclear Medicine, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200025, China.
3
Department of Pathology, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200025, China.
4
Clinical Laboratory, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai 200025, China.
5
Department of Epidemiology and Center for Global Cardiometabolic Health, School of Public Health, Department of Medicine (Endocrinology), The Warren Alpert Medical School, Brown University, Providence, RI, USA.
6
Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China. Electronic address: gning@sibs.ac.cn.
7
Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China. Electronic address: wangjq@shsmu.edu.cn.
8
Department of Endocrine and Metabolic Diseases, Rui-jin Hospital, Shanghai Jiao-tong University School of Medicine, Shanghai Institute of Endocrine and Metabolic Diseases, Shanghai Clinical Center for Endocrine and Metabolic Diseases, Shanghai 200025, China. Electronic address: ljm10586@rjh.com.cn.

Abstract

BACKGROUND:

Parathyroid hormone related protein (PTHrP) triggers white adipose tissue (WAT) browning and cachexia in lung cancer mouse models. It remains unknown whether excessive PTH secretion affects WAT browning and to what extent it contributes to body weight change in primary hyperparathyroidism (PHPT).

METHODS:

Using the adeno-associated virus injection, Pth gene over-expressed mice mimicking PHPT were firstly established to observe their WAT browning and body weight alteration. The association between PTH and body weight was investigated in 496 PHPT patients. The adipose browning activities of 20 PHPT and 60 control subjects were measured with PET/CT scanning.

FINDINGS:

Elevated plasma PTH triggered adipose tissue browning, leading to increased energy expenditure, reduced fat content, and finally decreased body weight in PHPT mice. Higher circulating PTH levels were associated with lower body weight (β = -0.048, P = .0003) independent of renal function, serum calcium, phosphorus,and albumin levels in PHPT patients. PHPT patients exhibited both higher prevalence of detectable brown/beige adipose tissue (20% vs 3.3%, P = .03) and increased browning activities (SUV in cervical adipose was 0.77 vs 0.49,P = .02) compared with control subjects.

INTERPRETATION:

Elevated serum PTH drove WAT browning program, which contributed in part to body weight loss in both PHPT mice and patients. These results give insights into the novel pathological effect of PTH and are of importance in understanding the metabolic changes of PHPT. FUND: This research is supported by the National Key Research and Development Program of China and National Natural Science Foundation of China.

KEYWORDS:

Adipose tissue browning; Body weight; Parathyroid hormone; Primary hyperparathyroidism

PMID:
30528454
DOI:
10.1016/j.ebiom.2018.11.057
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