Insulin sensitivity in mesolimbic pathways predicts and improves with weight loss in older dieters

Central insulin is involved in the regulation of hedonic feeding. Insulin
resistance in overweight has recently been shown to reduce the inhibitory
function of insulin in the human brain, but how this affects future weight
management is unclear. Also unknown is the role of central insulin
sensitivity on eating behavior of older people, who are highly vulnerable
to hyperinsulinemia and in whom neural target systems of insulin action
undergo age-related changes. Here, fifty overweight, pre-diabetic elderly
participated in a double-blind, placebo-controlled pharmacological fMRI
study before and after randomization to a 3-month caloric restriction or
active waiting group. We show that treatment outcome in dieters can be
predicted by baseline measures of individual intranasal insulin (INI)
inhibition of value signals in the ventral tegmental area related to sweet
food liking as well as, independently, by peripheral insulin sensitivity.
At follow-up, both INI inhibition of hedonic value signals in the nucleus
accumbens and whole-body insulin sensitivity improved with weight loss.
These data highlight the critical role of central insulin function in
mesolimbic systems for future weight management in humans and directly
demonstrate that neural insulin function can be improved by weight loss
even in older age, which may be essential for preventing metabolic
disorders in later life.