In this study, we measured the dose-response relationship of BMI and LDL-C in Asian population, and further explored the association between BMI and LDL-C in sex subgroup and different MS status. It has been found that, in the population with normal or light weight (BMI < 22.5 kg/m2), the association between BMI and LDL-C was linearly and positively correlated, in the overweight population, with the increase of BMI, the level of LDL-C gradually tended to be flat or even decreased. The trend of the above association was also different between genders, and the inverted-U shape was showed in male.
The association between BMI and lipid metabolites was assessed chiefly in HDL-C or triglyceride levels with the result of linear association, but the dose-response relationship of BMI and LDL-C has occasionally been carried out and the result remains inconsistent. Several studies have indicated a positive association between BMI and LDL-C [17–20], whereas other studies have showed different findings [21, 22]. A study performed with two cross-sectional nationally representative data from the U.S. and Spain found an inverted U-shaped association between BMI or WC and LDL-C [6], which is consist with a similar study with the nondiabetic American Indians [22]. In addition, some studies suggested that association between BMI and LDL-C differ between sex and age subgroup [20, 23]. Although the above studies have initially pointed out the association between BMI and LDL-C, it is limited to the European and American population, and most of the studies only explored the single sex. This study based on the Chinses population, estimating the ascending and descending slopes, as well as inflection points, comprehensively discussing the association between BMI and LDL-C in sex, age, and MS statues subgroups.
The results of the present study suggested that, based on the Chinese population, the association between BMI and LDL-C showed as an inverted U-shape, which is consist with previous two studies conducted with the U.S. and Spain populations [6, 22]. While WC and LDL-C showed as an inclined S-shape. The above epidemiological findings have also been supported by the studies of biological mechanisms. In particular, in non-obese people (BMI < 25 kg/m2), triglycerides are converted into cholesterol rich intermediate density lipoprotein (IDL) and LDL for adipogenesis, leading a positive correlation between BMI and LDL in the lean individuals [6]. However, triglycerides may be stored in very low density lipoprotein (VLDL) when lipid deposition in adipose tissue reaches the maximum limit or other exists lipid metabolism disorders, resulting in a decrease in the formation of LDL [24]. Another possible explanation is that adipose tissue store large amounts of cholesterol, thus buffering the cholesterol load of the liver [25]. A study has pointed out that the secretion of bile cholesterol in obese people increases gradually with the accumulation of adipose cell [26]. Therefore, in obese people, normal LDL-C levels may suggest that increased adipocytes are maintaining cholesterol homeostasis. In addition, our study first found that the association between WC and LDL-C showed as an inclined S-shape, which is inconsistent with the association between BMI and LDL-C and the results of previous study. It is well known that the obesity types and fat distribution of Asians and Westerners are different. In addition, with the increase of weight, adipose cell is more likely to accumulate in the abdomen for men, while it is more likely to accumulate in the lower body for woman [27]. Therefore, the gender ratio of the included population will lead to differences in results. Taken together, both ethnic differences and the sex ratio of the recruited subjects may cause the inconsistence, however, more direct evidence of the underlying mechanism regarding the association will be needed.
The performance of the association between BMI and LDL-C in sex subgroup has also been investigated. The inverted U-shape is obviously showed in the male group while it disappeared in the female group. The majority of studies on the above-mentioned associations are carried out in a single sex, especially in men. Moreover, previous study suggested that, after avoiding the confounding factor of body fat percentage, the association of physical fitness level and that plasma lipid profiles between male and female is different [28]. In addition, subjects included in our study are over 45 years old, and a study indicated that the level of LDL-C has been affected by menopausal status, i.e., post-menopause female have higher concentrations of LDL-C [29–31]. Thus, we assume that differences in hormonal status between male and female may lead to different associations between BMI and LDL-C. Some studies have shown that BMI and LDL-C have a positive linear relationship in female. Quantitative studies have also shown that LDL-C of female with BMI between 27.1 kg/m2 and 30.0 kg/m2 increased by 17 mg/dl compared with subjects whose BMI between 21.1 kg/m2 and 23.0 kg/m2 [23]. This study also found that LDL-C increased with BMI, moreover, it is first time showed that there were two turning points in the association between BMI and LDL-C, that is, the slope began to flatten near the edge of obesity, and gradually increased again when BMI reached 27.0 kg/m2. Although we speculate that hormonal status may be responsible for above association, the specific mechanism remains to be further investigated.
Our results supported that the MS status played a role in the association between BMI and LDL-C, i.e., with aggravation of metabolic impairment (number of MS criteria), the turning point of the association curve between BMI and LDL-C gradually appeared earlier. In the extreme group that the subjects had three or four MS criterias, the association trend in male was weakened, while it was more unstable in female. Similar results have been reported in the US population previously [6], while this study further investigated the sex subgroups separately and provided a thorough and detailed dose-response relationship between BMI and LDL-C. It is well known that MS is related to the increase of BMI. A study even pointed out that MS is caused by the abnormal function of adipose tissue, that is, adipose tissue reached the limit of functional capacity. Another reason may be that, in the regulation of homeostasis mechanism, lipid transport cholesterol may reduce the risk of diabetes and produce high levels of LDL-C. However, after the homeostasis mechanism broken, abnormal cholesterol synthesis and transport will also break the linear relationship between BMI and LDL-C.
Two limitations of this study are addressed. First, this study is a cross-sectional study, which is not able to explain the causal relationship between BMI and LDL-C. Second, in this study, the number of MS criteria was used to represent the severity of MS, where need more accurate quantitative indicators to explore the association between BMI and LDL-C.