WHO reported that 13% of the global population of adults were obese in 2016 [1], and it is projected that 1 in 5 adults will be obese in 2025 [2]. The etiology of obesity is attributed to a complex interaction between overnutrition, sedentariness, and genetic factors [3]. Obesity incidence have increased significantly in Indonesia between 2007 (10.5%) and 2018 (21.8%) [4, 5]. There is a growing interest in the genetic predisposition of obesity in Indonesia, since mortality due to obesity comorbidities have risen to the nation’s top [6, 7].
As a common risk factor, the fat mass and obesity-associated (FTO) association with obesity is well-documented, particularly in Caucasian populations, albeit the overall risk is modest [8–12]. Single nucleotide polymorphism (SNPs) in the FTO gene were associated with other obesity traits (e.g., body weight, leptin levels, body fat, waist circumference) [8–14]. East and South Asian populations showed comparable associations for common FTO variants (notably rs9939609, rs1558902, and rs1421085) [13–18], but the effect size may vary depending on ethnicity and dietary intake [19, 20]. Concurrent associations between FTO variants, obesity, and dietary intake have been noted in several ethnic groups [19–22], including our previous report that FTO rs9939609 TT genotype was associated with obesity and preference for a high-fat diet in adult individuals from Jakarta [23].
Overexpression of the FTO gene in the hypothalamus can regulate energy balance and appetite [3]. FTO rs9939609 is associated with elevated intake of polyunsaturated fatty acid (PUFA) and saturated fatty acid (SAFA), as well as with obesity, in children and adolescents in a Spanish population [24]. We expect that a similar influence can be observed for FTO rs1421085 – an intronic T→C mutation that has high linkage disequilibrium with FTO rs9939609 [23]. Several studies showed that FTO rs1421085 is associated with both obese-related phenotypes and dietary macronutrient intake [13, 14, 25]. In vivo and in vitro model studies showed that FTO rs1421085 can alter the binding of transcriptional repressors in nearby regions, affecting the expression of genes linked to adipocyte thermogenesis and food intake [26, 27].
Understanding the interaction between diet and FTO variants in Indonesia may provide invaluable insights for the management of obesity in the country, given that Indonesian cuisine is naturally fatty, owing to generous use of coconut milk and palm oil [28–30]. Dietary fat and SAFA intake in Indonesia was among the highest of countries across the globe (31.9% and 20.9%, respectively) [31].
As a continuation of our previous study [23], we performed genotyping for FTO rs1421085 and analyzed its association with obesity and dietary intake. We hypothesize that individuals with the minor risk allele have higher Body Mass Index (BMI), higher fat intake, and distinct fatty acid intake profile (PUFA, monounsaturated fatty acid/MUFA, and SAFA). Our findings provided valuable insights into the influence of the FTO rs1421085 risk allele on BMI and individual preferences for consuming more fat, particularly MUFA and SAFA.