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102 cm in men and >

88 cm in women and a WHR >

0.90 for men and >

0.85 for women indicates obesity and can be used to predict T2DM, hypertension, cardiovas- cular disease, gall bladder disease and specific cancers [13,14]. Certain studies on Asian populations have shown that the Chinese have more body fat at a lower BMI and WC than Western popula- tions [15,16]. Therefore, the waist-height ratio (WHtR) index *Address correspondence to this author at the River Branch Professor &

Division Chief University of Florida, Departments of Psychiatry and Neuro- science McKnight Brain Institute

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E-mail: [email protected] appears to be an even more reliable measurement of obesity for lower statue ethnic groups such as the Chinese [17]. Studies have shown that obesity can be linked to lower ghrelin concentrations in obese individuals [18,19,20]. Salivary ghrelin levels were lower in obese and non-obese subjects with T2DM [21]. Ghrelin levels have been found to be negatively correlated with body fat and WC [22]. Serum and saliva ghrelin levels were corre- lated with BMI [23]. Saliva has been used as a simple, non-invasive diagnostic tool [24]. Parotid and submandibular glands were the primary sources of ghrelin [23]. Hence, this may be a useful appli- cation in Chinese obesity clinics. In the following sections, the potential causes for obesity in China will be discussed in detail. GENE-ENVIRONMENT INTERACTION Gene-environment interaction is defined as the response or the adaptation to an environmental agent, a behavior, or a change in behavior is conditional on the genotype of the individual [25]. Mechanisms for this phenomenon consist of decreased resting me- tabolism and lipid oxidation rate, and poor appetite control with increased fat mass [26]. McMillen et al. [27] suggested that specific periods during pregnancy predisposed individuals to obesity, there- fore maternal nutrition and perinatal lifestyle played a major role in fetal programming. Over-nutrition during pregnancy led to larger offspring or gestational diabetes associated with obesity, while breastfeeding could counter the effects of obesity [28]. For exam- ple, in Fujian province, the rate of obesity has increased due to poor nutrition before and during pregnancy, economic development, urbanization and improved living standards [29]. Two recent studies [30,31] identified novel genetic variants associated with obesity and/or BMI. The genetic loci were: NEGR1, SEC16B-RASAL2, TMEM18, SFRS10-ETV5-DGKG, GNPDA2, NCR3-AIF1-BAT2, LGR4-LIN7CBDNF, MTCH2, BCDIN3D- FAIM2, SH2B1-ATP2A1, KCTD15, FTO (fat mass and obesity associated) [32,33,34] and MC4R (melanocortin

4 receptor) [35,36]. The FTO gene is present in all tissues and encodes a non-heme (FeII)-dioxygenase that adapts to hypoxia, lipolysis, or DNA meth- ylation [37,38]. This key protein may serve as a link between the central nervous system and energy homeostasis. Several studies associated FTO variants (rs8050136 and rs9939609) with obesity and BMI in Hong Kong, Taiwan, and Sin- gapore populations [32,33,34]. On the other hand, Li et al. [39] found no association of the FTO variants with obesity and BMI in Shanghai and Beijing individuals. Obesity-associated genetic vari- Obesity in China: What are the Causes? Current Pharmaceutical Design, 2011, Vol. 17, No.

12 1133 ants studied in Caucasians impacted the development of obesity in the Chinese. For all obesity-associated single-nucleotide polymor- phisms (SNPs), researchers observed higher odds ratios than previ- ously reported [30,31]. This may be caused by differences in ge- netic compositions between Chinese and Caucasian populations, even though these SNPs are less common in the Chinese. There was a 17-23% increased risk of obesity for every unit increase in the combined genetic risk scores. Further research needs to be done on obesity susceptibility genes for clinical applications. The estimated heritability of BMI in Chinese ranged from 0.42 to 0.54 [40,41,42];