ESPE Yearbook of Paediatric Endocrinology

Brief summary: This randomized, controlled study in healthy-weight individuals examined the effect of a daily high-fat/high-sugar (HF/HS) intervention over 8 weeks on fat and sugar preference, alterations of brain response to food and sensory associative learning. It addressed the question, whether the association between obesity and altered brain function is pre-existing, is secondary to obesity or is attributed to western diet.

Current models of obesity consider genetic predisposition to be the cause for obesity in an obesogenic environment (1–3). However, preclinical studies provide evidence that frequent consumption of modern unhealthy processed foods, rich in fat and sugar, rewires brain circuits and shifts our preferences away from low-fat and healthy foods (4–6). Prior neuroimaging studies showed that sweet beverages as well as saturated fat alters striatal response (7,8).

These authors found that a subtle exposure to high-fat/high-sugar (HF/HS) foods (2 snacks per day) in addition to regular diet reduces preferences for low-fat foods (liking and wanting) in healthy-weight participants. Moreover, they showed by fMRI that HF/HS snacks alter brain reward circuits to palatable food and upregulate neural computations that support adaptive associative learning. The authors claim that these findings were independent of a change in BMI or metabolic parameters, although there was a slight gain in weight. In addition, it should be mentioned that there was also a significant reduction in preference for high-fat food in the HF/HS group, as well as a reduced wanting for high-fat food also in the control group, who received low-fat/low-sugar (LF/LS) snacks, and a reduced wanting and liking for low-sugar food in both groups.

Current models of obesity should be expanded based on the results of this well-designed study, which results suggest that the cycle of overeating may begin with environmental exposure rather than, or in addition to, a predisposition for obesity.

References: 1. Rankinen T, et al. The human obesity gene map: the 2005 update. Obesity 2006;14:529–644. 2. Frayling TM, et al. A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity. Science 2007;316:889–894. 3. Loos RJF, Yeo GSH. The genetics of obesity: from discovery to biology. Nat. Rev. Genet. 2022;23:120–133. 4. Tellez LA, Medina S, Han W, Ferreira JG, Licona-Limón P, Ren X, Lam TT, Schwartz GJ, de Araujo, IE. A gut lipid messenger links excess dietary fat to dopamine deficiency. Science 2013;341:800–802. 5. Sun X, Kroemer NB, Veldhuizen MG, Babbs AE, de Araujo IE, Gitelman DR, Sherwin RS, Sinha R, Small DM. Basolateral amygdala response to food cues in the absence of hunger is associated with weight gain susceptibility. J. Neurosci. 2015;35:7964– 7976. 6. DiFeliceantonio AG, Coppin G, Rigoux L, Edwin Thanarajah S, Dagher A, Tittgemeyer M, Small DM. Supra-additive effects of combining fat and carbohydrate on food reward. Cell Metab. 2018;28:33–44.e3. 7. Burger KS. Frontostriatal and behavioral adaptations to daily sugar-sweetened beverage intake: a randomized controlled trial. Am. J. Clin. Nutr. 2017;105:555–563. 8. Dumas JA, Bunn JY, Nickerson J, Crain KI, Ebenstein DB, Tarleton EK, Makarewicz J, Poynter ME, Kien CL. Dietary saturated fat and monounsaturated fat have reversible effects on brain function and the secretion of pro-inflammatory cytokines in young women. Metabolism 2016;65:1582–1588.