| 제목 |
Changes in Body Composition and Proinflammatory Marker Levels in Ovariectomized Rats |
| 소속 |
Pusan National University Hospital, Department of Rehabilitation Medicine1, Pusan National University Hospital, Department of Obstetrics and Gynecology2, Pusan National University Hospital, Department of Otorhinolaryngology3, Pusan National University Hospital, Department of Nuclear Medicine4, Pusan National University Yangsan Hospital, Department of Nuclear Medicine5, Pusan National University Hospital, Department of Internal Medicine-Endocrine6, Pusan National University Hospital, Pusan National University Medical Research Institute7 |
| 저자 |
Mi-Kyung Cho1*, Young Mo Kim2, Young Joo Lee3, Byung-Joo Lee4, In-Joo Kim5, Seong-Jang Kim4, Kyoungjune Pak6, Yun Kyung Jeon7, Ji Min Kim7, Jeong Hun Kim1, Myung Jun Shin4, Yong Beom Shin1, Keunyoung Kim1, Jin A Yoon1† |
Introduction
This study examined the effect of TSH-suppressive dose of levothyroxin (LT4) on changes in body composition and pro-inflammatory markers in ovariectomized rats.
Method
Bilateral ovariectomy (OVX) and sham operations (Sham) were performed in female Sprague-Dawley virgin rats at 7 weeks of age. Rats were divided into four experimental groups of Sham, Sham+LT4, OVX, and OVX+LT4. Eight weeks after surgery, the body composition was analyzed using dual-energy X-ray absorptiometry (DXA), along with measurements of serum levels of pro-inflammatory parameters.
Result
The amount of weight gain was significantly higher in the OVX than in the Sham groups (median: 104.6; IQR: 91.27-116.8 vs. median: 66.4; IQR: 61.5-71.2, P=0.001), and administration of LT4 did not have an effect on body weight in either group. (Fig. 1.) The fat mass, but not lean mass, was significantly increased in the trunk area of rats in the OVX group compared with control group, regardless of LT4 treatment. (Fig. 2.) Among the pro-inflammatory cytokines, the serum level of C-reactive peptide, interleukin (IL)-6, and IL-10 was significantly increased in the OVX group, and only IL-6 could be further increased upon additional treatment with LT4. (Table 1.)
Discussion
Nowadays, a concept of the combination of reduced muscle mass and increased fat volume, known as obesity-related sarcopenia or sarcopenic obesity (SO) has emerged. The reduced lean body mass and increased fat mass in OVX rats indicates that menopause induces obesity-related sarcopenic changes. In our study, the weight gain due to increased fat mass in trunk area was different between ovariectomized rats and controls, regardless of the TSH suppressive therapy. Although total mass increased, we did not find a significant change in the lean body mass, and the decreasing trend of lean mass in the trunk area due to TSH suppressive LT4 treatment was similar in both OVX and Sham groups
Reduced and weakened muscle quality in OVX is inevitable because estrogen functions to resolve the inflammatory response and to accelerate muscle healing through proliferation and activation of the muscle fiber satellite cells. In accordance with previous reports, our findings showed that the change in body composition, characterized as a combination of reduced muscle mass and excess body fat, was associated with elevated inflammatory markers, CRP and IL-6, but not TNF-α, which was associated with SO‐related phenotypes in postmenopausal women. In addition, Further, the elevated level of inflammatory cytokines in OVX+LT4 group indirectly suggests that menopause and TSH suppressive therapy might raise the risk of cardiovascular disease.
Conclusion
The results of our study have clinical implications for considering TSH suppressive therapy
as a latent risk factor for overall survival. We propose that body composition and muscular function should be evaluated in menopausal patients being considered for long-term TSH-suppressive therapy. |
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Figure 1. Serial changes of the body weight during experiment
Figure 2. Effects of ovariectomy (OVX) and TSH-suppressive (LT4) treatment on body weight and body composition
Table 1. Effects of ovariectomy and LT4 treatment on cholesterol level and proinflammatory markers
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