The present study showed significant differences in fasting insulin levels and insulin resistance between NWO and NWNO women. Leptin was significantly higher in women with NWO compared to NWNO women. The serum level of vaspin was higher in the NWO compared to the NWNO group, but this difference was not statistically significant.
Previous studies have shown that patients with NWO have higher prevalence of cardiometabolic abnormalities compared to subjects with normal weight and body fat mass. Huang and colleagues conducted the investigation among young Japanese females and demonstrated that NWO women had higher level of fasting insulin than lean women or those with NWNO (non-significant), but it was lower compared to the obese women (P = 0.003). Although, similar results were reported for HOMA-IR, but the HOMA-β index was higher in the NWO women compared to lean or NWNO women, and was lower compared to the obese women.
Fat mass is more likely to accumulate in the upper body in Asian women compared to Caucasian whites with similar BMI. For this reason, Asian women with normal BMI are more susceptible to NWO and having higher WHR. Therefore, body fat mass deposition and distribution are influenced by race
Madeira et al. conducted a study on 1222 men and women in Brazil and found that normal-weight obesity was associated with HOMA-IR, low insulin sensitivity, and high insulin secretion.
It has been reported that despite having a normal body weight, there is a positive association between increased body fat tissue and cardiometabolic disorders among adolescents. Heijden et al. (2018) showed statistically significant higher abdominal and hepatic fat content, insulin resistance, circulating leptin, and Hs-CRP (high sensitive C-reactive protein) concentrations in Hispanic adolescent girls with normal BMI (< 85th percentile) and high body fat (≥ 27%) compared to the control group .
Previous studies have shown that individuals with NWO are susceptible to metabolic syndrome and cardiovascular disease due to the higher prevalence of hyperglycemia, insulin resistance, low-grade pro-inflammatory state, increased oxidative stress, and increased hyperlipidemic disorders, which are influenced by higher body fat tissue in normal weight obesity[14-16].
The relationship between abdominal fat deposition and other components of metabolic syndrome was confirmed in numerous previous studies in various populations such as people with overweight and obesity, type 2 diabetes, metabolic syndrome, and postmenopausal women[17-19].
Wei et al. (2020) reported the disturbed adipokine profile in obese patients with newly diagnosed type 2 diabetes (T2D) compared to diabetic patients with normal BMI. Obese patients with T2D had a higher level of leptin and reduced concentration of adiponectin compared to non-obese T2D patients. The results obtained from this study and previous investigations may explain the relationship between three parts, including fat mass, adipokines, and cardiometabolic abnormalities like a triangle with multiple interactions and feedbacks. However, more studies are needed to demonstrate the cellular and molecular mechanism of interaction between adipokines at the cellular level and endocrine disorders at the clinical level. The association between excessive body fat tissues and components of metabolic syndrome can be described via adipokine secretion. The present study showed that serum levels of leptin and vaspin were higher in the NWO women compared to the participants in the control group. Present results indicating an increase in the concentration of leptin are consistent with previous studies. Romero-Corral et al. (2010) reported a higher concentration of leptin among American individuals with NWO, which is in line with current findings. Another study conducted in Switzerland showed a higher concentration of leptin in women with NWO than women with normal BMI and FM%.
It was confirmed that obese patients had a higher level of leptin compared to individuals with normal weight, which might be due to the leptin resistance in obesity. Leptin is one of the adipocytokine secreted by adipose tissues, and plays important roles in regulation of body weight and energy homeostasis. Moreover, according to previous studies, there is a positive relationship between the blood level of leptin and body fat percentage. Likewise, we observed similar result among women with NWO (r = 0.36, P = 0.02). Secondary outcomes of the present study revealed a positive association between leptin concentration with FBS, fasting level of insulin, and HOMA-IR.
Evidence from literature on leptin showed paradox actions. Leptin may promote atherogenesis processes and insulin resistance and on the other hand, it may exert antiatherogenic effect and increase insulin sensitivity. Koh et al. reported that the opposite effects of leptin are in balance in healthy people and disrupted in obesity. The effect of leptin in increasing insulin resistance in women with NWO is similar to patients with obesity. Otherwise, leptin has a positive correlation with the markers of pro-inflammatory and inflammatory conditions, which can describe the role of a higher level of leptin in increasing the risk factors of cardiometabolic disorders[25, 26].
Similar to leptin, a statistically significant association was found between vaspin concentration with fasting insulin level and HOMA-IR in women with NWO.
Vaspin, a serine protease inhibitor derived from visceral adipose tissue, has shown insulin sensitizing effects. An experimental study showed that injecting vaspin to obese mice can improve glucose tolerance by increasing insulin sensitivity. Compared to other adipokines, limited studies have investigated vaspin in humans, and most have focused on animal models of obesity and T2D.
Based on the physiological functions of adipokines, they are classified into two categories, including “healthy” adipokines such as adiponectin and omentin, and “unhealthy” adipokines. However, in addition to TNF-α, other adipokines including IL‐6, plasminogen activator inhibitor-1, adipocyte fatty acid‐binding protein, lipocalin-2, chemerin, visfatin and resistin, vaspin, and leptin are assumed as unhealthy adipokines.
Based on the results of Genske, et al. (2018) among 1825 participants about the associations between vaspin and distribution of fat tissues, including visceral adipose tissue (VAT), subcutaneous adipose tissue (SAT), or liver fat content (LFC), no clear conclusion has been reached. Endogenous vaspin is positively associated with insulin signaling in 3T3-L1 cells, which could be described by the role of vaspin in increasing insulin-stimulated phosphorylation of key mediator protein kinase B.
On the other hand, the result of an experimental study in mice reported that injection of insulin in fasting status increase the hepatic expression of vaspin. Previous studies have indicated that serum concentration of vaspin was increased with worsening insulin resistance in children and impaired glucose tolerance and obesity in adults [32-34].
Our results were consistent with previous studies in finding significant positive association between circulating vaspin and insulin in women with NWO. Therefore, it is suggested that circulating vaspin is increased as a compensatory response to elevated concentration of insulin and enhancing insulin resistance. Vaspin mRNA expression is higher in patients with T2D and obesity due to the higher percentage of FM. Patients with NWO have both impaired glucose intolerance and higher FM%. Regarding the compensatory effect of vaspin, Heiker et al. (2013) proposed increasing insulin sensitivity through the reduction of kallikrein 7 (hk7) as an insulin degrading. They demonstrated that hk7 may act as a target of the protease action of vaspin in human tissues.
Moreover, chronic low-grade inflammation is induced in obesity due to higher body fat mass. Previous studies have shown that vaspin may inhibit inflammatory processes by regulation of the peroxisome proliferator-activated receptor (PPAR). More studies are needed to find the mechanism behind the effect of adipokines on glycemic responses in NWO patients.
According to our knowledge, this is the first study investigating the changes in serum level of vaspin in individuals with NWO. More studies are required to observe the changes in the serum concentration of adipokines and their interaction with one another and the components of metabolic syndrome.
The main limitation of this study is the small size of its sample. Further prospective studies with larger sample size are needed to investigate the causality of correlation between adpokines and metabolic abnormalities.