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

TY - JOUR

T1 - Insulin sensitivity in mesolimbic pathways predicts and improves with weight loss in older dieters

AU - Tiedemann, Lena J

AU - Meyhöfer, Sebastian M

AU - Francke, Paul

AU - Beck, Judith

AU - Büchel, Christian

AU - Brassen, Stefanie

N1 - © 2022, Tiedemann et al.

PY - 2022/9/27

Y1 - 2022/9/27

N2 - Central insulin is critically 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. How this relates to effective weight management is unclear, especially in older people, who are highly vulnerable to hyperinsulinemia and in whom neural target systems of insulin action undergo age-related changes. Here, 50 overweight, non-diabetic older adults participated in a double-blind, placebo-controlled, pharmacological functional magnetic resonance imaging study before and after randomization to a 3-month caloric restriction or active waiting group. Our data 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 peripheral insulin sensitivity improved with weight loss. These data highlight the critical role of central insulin function in mesolimbic systems for 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.

AB - Central insulin is critically 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. How this relates to effective weight management is unclear, especially in older people, who are highly vulnerable to hyperinsulinemia and in whom neural target systems of insulin action undergo age-related changes. Here, 50 overweight, non-diabetic older adults participated in a double-blind, placebo-controlled, pharmacological functional magnetic resonance imaging study before and after randomization to a 3-month caloric restriction or active waiting group. Our data 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 peripheral insulin sensitivity improved with weight loss. These data highlight the critical role of central insulin function in mesolimbic systems for 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.

KW - Aged

KW - Humans

KW - Insulin

KW - Insulin Resistance

KW - Overweight

KW - Ventral Tegmental Area/physiology

KW - Weight Loss

U2 - 10.7554/eLife.76835

DO - 10.7554/eLife.76835

M3 - SCORING: Journal article

C2 - 36170006

VL - 11

JO - ELIFE

JF - ELIFE

SN - 2050-084X

M1 - e76835

ER -