FTO effect on energy demand versus food intake

Area of Science:

• Genetics and Obesity Research
• Metabolic Regulation Studies

Background:

• The intronic single nucleotide polymorphism (SNP) rs9939609 near the fat mass and obesity associated gene (FTO) is the first identified common variant linked to body mass index (BMI).
• Previous human studies associate rs9939609 with altered food intake and satiety, but not consistently with energy expenditure.
• Fischer et al. recently created Fto-inactivated mice (Fto(-/-)) demonstrating protection from obesity.

Purpose of the Study:

• To investigate the contrasting mechanisms of the FTO gene in human obesity versus Fto gene function in mice.
• To explore the role of FTO in metabolic rate and food intake regulation across species.

Main Methods:

• Analysis of existing human genetic association studies on SNP rs9939609 and its relation to food intake, satiety, and energy expenditure.
• Review of findings from Fischer et al. on Fto(-/-) mice, focusing on food intake and metabolic rate compared to wild-type littermates.

Main Results:

• Human studies link the FTO SNP rs9939609 to variations in food intake and satiety, with no consistent effect on energy expenditure.
• Fto(-/-) mice exhibited no significant difference in food intake but displayed an elevated metabolic rate, suggesting protection from obesity via increased energy expenditure.
• The observed effects in mice appear mechanistically opposite to those suggested by human studies of the FTO SNP.

Conclusions:

• The contrasting effects of FTO gene variants in humans and Fto gene function in mice warrant further investigation.
• The intronic SNP rs9939609's influence on obesity may involve complex, species-specific regulatory mechanisms impacting metabolism.