Sweet taste preference is associated with greater hypothalamic response to glucose and longitudinal weight gain

•The Monell procedure was used to assess preferences for sweet taste, and MRI was used to evaluate hypothalamic response to glucose ingestion, in adults with healthy weight, overweight, and obesity.•Sweet taste preference was positively associated with glucose-linked hypothalamic activation, a purported marker of obesity risk.•Higher sweet taste preference was associated with longitudinal increases in BMI. The hypothalamus has an abundant expression of sweet taste receptors that play a role in glucose sensing and energy homeostasis. Evidence suggests that liking “sweets” can be associated with weight gain, but the relationship between sweet taste preference and hypothalamic regulation of appetite is unknown. This study tested the hypothesis that sweet taste preference is associated with increased hypothalamic activation in response to glucose (a purported neural marker for weight gain risk) and greater longitudinal increases in body mass index (BMI). Fifty-four adults aged 18–35 years with a mean (± SD) BMI of 27.99 ± 5.32 kg/m2 completed the study. Height and weight were measured at baseline and 6–12 months later in a subset of 36 participants. Sweet taste preference was assessed via the Monell 2-series, forced-choice tracking procedure. Arterial spin labeling magnetic resonance imaging was performed before and after oral glucose ingestion to determine hypothalamic blood flow response to glucose. Linear models were used to examine relationships between sweet taste preference and the hypothalamic response to glucose and longitudinal changes in BMI, adjusting for age, sex, and baseline BMI. Sweet taste preference was positively associated with glucose-linked hypothalamic blood flow (beta = 0.017, p = 0.043), adjusted for age, sex and BMI. We also observed a positive association between sweet taste preference and longitudinal change in BMI (beta = 0.088, p = 0.015), adjusted for age, sex and baseline BMI. These findings suggest that heightened sweet taste preference is associated with glucose-linked hypothalamic activation and may be linked to increased susceptibility for weight gain.