Neural Mechanisms for Appetitive Responses to High Reward Foods

Animal studies have shown that fructose may act centrally to promote food intake. Compared to
glucose, fructose may also be a weak suppressor of appetite due to attenuated stimulation of
the purported satiety hormones, insulin and glucagon-like polypeptide-1 (GLP-1). Moreover,
fructose is sweeter than glucose and may stimulate central taste and reward pathways to
promote feeding behavior. The investigators have combined functional magnetic resonance
imaging (fMRI) with hormonal and behavioral assessments to better understand the impacts of
glucose and fructose on appetite and its central regulation in humans and have made important
observations in lean individuals linking fructose consumption to overeating and obesity. The
ingestion of fructose: (a) reduced cerebral blood flow (CBF), a marker of neuronal activity,
in the hypothalamus less than ingestion of glucose; (b) stimulated levels of two potential
satiety hormones, insulin and GLP-1, less than glucose; and (c) failed to induce the satiety
that was observed after glucose ingestion (Page et al, Journal of American Medical
Association 2013). The investigators now propose to expand this work by examining some
potential biological underpinnings of the different impacts of glucose and fructose
ingestion; examining responses to combinations of glucose and fructose ingested together, as
occurs in real life; and by examining effects of a common non-nutritive sweetener, sucralose,
on brain and appetitive response. The investigators propose a random-order crossover design
to determine the effects of caloric and non-nutritive sweeteners among lean, obese, and
obesity-prone groups of participants. The investigators will measure body fat, circulating
levels of hormones involved in satiety signaling, quantify food intake, and measure brain
activity using blood-oxygen level dependent and arterial spin labeling methods and functional
connectivity analyses.

Inclusion Criteria:

- Age 18-35 years, right-handed, weight change <2% for at least 3 months prior to
participation, no history of diabetes or other significant medical problems, fasting
glucose <126 mg/dl.

- Lean group: BMI of 19-25 kg/m2; report never having been overweight and report no
obese first degree relatives.

- Obese Group: BMI 30-40 kg/m2; Obesity-prone Group: BMI of 20-29 kg/m2; report at least
one first degree relative with a BMI >30 kg/m2; report having to put effort into not
gaining weight; report previous attempts to lose weight, but not actively attempting
to lose weight.

Exclusion Criteria:

- Neurological, psychiatric or addiction disorder, fasting glucose ≥126 mg/dl, use of
prescription medication (with the exception of contraceptives), tobacco use,
contraindications to MRI scanning (detailed in Protection of Human Subjects), fructose
intolerance, history of eating disorder, actively trying to lose weight.