Effects of Insulin Resistance on Brain Responses to Caloric Sugars and Nonnutritive Sweetener

Evidence suggests that insulin resistance (IR) affects feeding behavior by modulating neural responses to post-ingestive signals, including nutrients and taste. We examined associations between IR and activation of the hypothalamus and insula, brain regions involved in homeostasis and taste processing, to ingestion of sugars and the non-nutritive sweetener (NNS) , sucralose. Seventy-four participants (23.4±4 years; 42%male; BMI 27.2±5; HOMA-IR 5.3±5) completed 4 MRI visits with ingestion of drinks containing 75g sucrose, 75g glucose, sucralose, or water in a randomized cross-over design. Arterial spin labeling MRI was performed before, 15min and 30min after drink ingestion to measure cerebral blood flow (CBF) . Primary outcomes were associations between HOMA-IR and hypothalamic and insular CBF responses to glucose vs. sucrose, sucralose vs. water, and sucrose vs. sucralose. Mixed effects models included the following factors: drink contrasts, sex, time point, and BMI and HOMA-IR as continuous variables. Bonferroni-Holm was used to adjust for multiple comparisons. In the hypothalamus, HOMA-IR, independent of BMI, was associated with a greater hypothalamic CBF response to sucralose vs. water (p<0.03) , but there was no association between HOMA-IR and hypothalamic response to sugar. In the insula, there was a drink by HOMA-IR interaction in the insular response to sucralose vs. water (p<0.02) ; persons with IR showed greater increases in CBF after sucralose vs. water. We also found a main effect of HOMA-IR; persons with higher IR had greater insular CBF increases to sugar (p<0.05) , and a drink by HOMA-IR interaction revealed a stronger association between IR and insular response to glucose vs. sucrose (p<0.03) . There was no association between HOMA-IR and brain responses to sucralose vs. sucrose. These findings show that IR is associated with greater activation of brain regions involved in taste and energy homeostasis to ingestion of sugar and NNS, which may promote eating behavior. Disclosure S. Kullmann: Other Relationship; Novo Nordisk. R. Veit: None. K. Jann: None. S.H. Luo: None. B.C. Angelo: None. J.M. Alves: None. J.R. Monterosso: None. K.A. Page: None. Funding NIDDK R01DK102794