Original articleAssociations of serum fibroblast growth factor 23 levels with obesity and visceral fat accumulation
Introduction
Obesity can occur when the imbalance of energy intake and expenditure persists for a prolonged period. With the imbalance in energy metabolism, excess body fat accumulates and further predisposes individuals to developing metabolism disturbance and cardiovascular disease (CVD) [1]. Through the secretion of a variety of adipokines, adipose tissue contributes to metabolic alterations, cardiovascular morbidity, and bone health. The functions of adipose tissue vary with the fat distribution. The accumulation of visceral fat, instead of subcutaneous fat, is largely responsible for the effects of excess adipose tissue on CVD, diabetes, and mortality [2]. Emerging evidence indicates that the skeleton is involved in homeostatic processes of energy balance and adipose metabolism, and the adipokines and bone-derived factors compose part of a bone-adipose axis, leading to interaction between skeleton and fat to establish a homeostatic feedback system [1], [3].
As a bone-derived factor, fibroblast growth factor (FGF) 23 has similar structure and biological function to the other members of endocrine FGF subfamily, such as FGF19 and FGF21 [4]. Previous studies have provided evidence supporting the associations of FGF19 and FGF21 with overall and central obesity [5], [6]. Functioning as a circulating hormone, FGF23 is generally acknowledged as a central regulator in mineral homeostasis [4]. Recent findings raise the possibility that FGF23 also may be related with fat contents and distribution [7], [8], [9], [10], [11]. Animal studies have revealed FGF23-deficient mice are characterized by reduced fat content and alterations in fat distribution [7]. Additionally, several clinical studies have reported that circulating FGF23 levels are elevated in the obese population and associated with waist circumference (W) [8], [9], [10], [11].
Although W is a simple and recognized index used to identify central obesity, it is not an accurate indicator of visceral fat accumulation and distribution. The present study aimed to elucidate the relationships between serum FGF23 levels and the fat contents and distribution, with the precise indexes of abdominal fat (visceral fat area [VFA] and subcutaneous fat area [SFA]) assessed by magnetic resonance imaging (MRI). In order to eliminate the influences of hyperglycemia and kidney function on serum FGF23 levels, the study population included only normoglycemic individuals with preserved kidney function. Based on known gender differences in fat content and distribution [12], we divided the participants into three subgroups of men, premenopausal women, and postmenopausal women for analysis.
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Subjects
Normoglycemic individuals with normal renal function (estimated glomerular filtration rate ≥60 mL/min/1.73 m2) were selected from the Shanghai Obesity Study cohort [3]. Individuals with impaired glucose regulation or diabetes, diagnosed on the basis of the 1999 World Health Organization criteria [13], were excluded. Further exclusion of individuals with hepatic dysfunction, hyperthyroidism or hypothyroidism, hypercalcemia or hypocalcemia, acute infection, a history of tumors, psychiatric
Clinical characteristics of participants
The 1599 included study participants had a median age of 52.78 (45.98–57.84) years (overall age range: 20–78 years) and included 597 men, 411 premenopausal women, and 591 postmenopausal women. Among normal weight participants, age, BMI, W, systolic BP, diastolic BP, FPG, 2hPG, FINS, HOMA-IR, TC (P = 0.01), TG, LDL-c, CRP, VFA, and SFA were significantly greater (all P < 0.01) for those with abdominal obesity compared with those without abdominal obesity. In addition, the proportion of women and
Discussion
The present study revealed that for men and postmenopausal women, serum FGF23 levels were increased significantly in those with abdominal obesity. For men, the presence of abdominal obesity contributed independently to an increase in serum FGF23 levels regardless of the presence of overweight/obesity. For postmenopausal women, however, the presence of overweight/obesity and abdominal obesity, separately or jointly, contributed independently to an increase in serum FGF23 levels. Neither the
Funding sources
This work was funded by 973 Program of China (2013CB530606), Grant from Shanghai Health and Family Planning Commission (2013ZYJB1001), and Translational Medicine Innovation Foundation of School of Medicine Shanghai Jiao Tong University (15ZH2010 and 15ZH4006).
Conflict of interest statement
The authors have nothing to disclose.
Statement of authorship
The present study was designed by Yuqian Bao and Weiping Jia. Xiaojing Ma, Xiang Hu, Yuqi Luo, Yiting Xu, and Qin Xiong collected the data. Xiang Hu carried out the statistical analyses and composed the paper. Xiaoping Pan conducted the FGF23 assessment. Yunfeng Xiao assessed the abdominal fat by magnetic resonance imaging. Xiang Hu, Xiaojing Ma, Yuqian Bao, and Weiping Jia revised the paper and made contributions to the discussion. Xiang Hu and Xiaojing Ma had equal contribution to this paper
Acknowledgments
We appreciate the helps from all the staff of Baoshan, Gonghexin, Tianmuxi, and Daning communities. We are also much grateful to all participants for their dedication in data collection and laboratory assessments.
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These two authors contributed equally to this work.