Ramadan Diurnal Intermittent Fasting Is Associated With Attenuated FTO Gene Expression in Subjects With Overweight and Obesity: A Prospective Cohort Study

Abstract

Aim and BackgroundA growing body of evidence supports the impact of intermittent fasting (IF) on normalizing body weight and that the interaction between body genes and environmental factors shapes human susceptibility to developing obesity. FTO gene is one of these genes with metabolic effects related to energy metabolism and body fat deposition. This research examined the changes in FTO gene expression upon Ramadan intermittent fasting (RIF) in a group of metabolically healthy subjects with overweight and obesity.MethodsSixty-three (63) subjects were recruited, of which 57 (17 males and 40 females, mean age 38.4 ± 11.2 years) subjects with overweight and obesity (BMI = 29.89 ± 5.02 kg/m2were recruited and monitored before and at the end of Ramadan month), and 6 healthy subjects with normal BMI (21.4 ± 2.20 kg/m2) recruited only to standardize the reference for normal levels of FTO gene expression. In the two-time points, anthropometric, biochemical, and dietary assessments were undertaken, and FTO gene expression tests were performed using RNA extracted from the whole blood sample.ResultsIn contrast to normal BMI subjects, the relative gene expressions in overweight/obese were significantly decreased at the end of Ramadan (−32.30%, 95% CI–0.052 −0.981) in comparison with the pre-fasting state. Significant reductions were found in body weight, BMI, fat mass, body fat percent, hip circumference, LDL, IL-6, TNF-α (P<0.001), and in waist circumference (P<0.05), whilst HDL and IL-10 significantly increased (P<0.001) at the end of Ramadan in comparison with the pre-fasting levels. Binary logistic regression analysis for genetic expressions showed no significant association between high-energy intake, waist circumference, or obesity and FTO gene expression.ConclusionsRIF is associated with the downregulation of the FTO gene expression in subjects with obesity, and this may explain, at least in part, its favorable metabolic effects. Hence, RIF presumably may entail a protective impact against body weight gain and its adverse metabolic-related derangements in subjects with obesity.

Review of the Literature on Ramadan Fasting and Health in 2022

“…Several studies investigated the pathophysiological mechanisms of the impact of RF on some aspects of health 4 5 6 7 8 and nutritional changes including body composition and energy metabolism. 9 10 11 12 13…”

“…Several studies investigated the pathophysiological mechanisms of the impact of RF on some aspects of health [4][5][6][7][8] and nutritional changes including body composition and energy metabolism. [9][10][11][12][13] The effects of RF on nasal mucociliary clearance (MCC) and peak nasal inspiratory flow (PNIF) were evaluated in a prospective study that included 62 healthy subjects intending to fast.…”

Eating, diet, and nutrition for the treatment of non-alcoholic fatty liver disease

“…Again, aside from the improvement in metabolic serum parameters including glucose homeostasis 151 , noninvasive scores of fibrosis and markers of subclinical inflammation improved in NAFLD patients 152 . Also, Ramadan fasting reduced the gene expression of "fat-mass-andobesity-associated protein" (FTO) in overweight/obese individuals 153 , which has been associated with obesity 154 despite lower calorie intake 155 . However, it is currently a matter of debate whether IF (i.e., time-dependent calorie restriction) is more effective 156 or equally effective 157,158 than continuous calorie restriction (e.g., hypocaloric diet), and whether it is effective if no calorie restriction/dietary counselling is applied 159 .…”

“…Again, aside from the improvement in metabolic serum parameters including glucose homeostasis [ 151 ], non-invasive scores of fibrosis and markers of subclinical inflammation improved in NAFLD patients [ 152 ]. Also, Ramadan fasting reduced the gene expression of “fat-mass-and-obesity-associated protein” (FTO) in overweight/obese individuals [ 153 ], which has been associated with obesity [ 154 ] despite lower calorie intake [ 155 ].…”

Genetics, genomics, and diet interactions in obesity in the Latin American environment

“…FTO regulates the expression of hepatic gluconeogenic genes such as G6PC (Glucose-6-phosphatase) and PCK (Phosphoenolpyruvate carboxykinase) by altering the activity and interaction with transcription factors such as STAT30 (Signal Transducers and Activators of Transcription 3), CREB (protein cAMP-responsive element binding), and ATF4 (activating transcription factor 4) ( 120 ). Increased FTO expression causes increased transcription of genes encoding gluconeogenic enzymes, leading to increased gluconeogenesis, while decreased FTO expression causes the opposite effect ( 121 ). For example, Doaei et al report that the FTO expression level in peripheral blood mononuclear cells increased in obese individuals ( 122 ).…”