Insulin sensitivity in mesolimbic pathways predicts and improves with weight loss in older dieters
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Curated by eLife
Evaluation Summary:
This is a paper that will be of particular interest to neuroscientists with a focus on food intake and neural responses to food ingestion. This paper provides new insights into how the body responds to weight loss and helps identify those that may not be successful.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
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Abstract
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.
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Evaluation Summary:
This is a paper that will be of particular interest to neuroscientists with a focus on food intake and neural responses to food ingestion. This paper provides new insights into how the body responds to weight loss and helps identify those that may not be successful.
(This preprint has been reviewed by eLife. We include the public reviews from the reviewers here; the authors also receive private feedback with suggested changes to the manuscript. The reviewers remained anonymous to the authors.)
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Joint Public Review:
Tiedemann et al. evaluated the neural response to insulin before and after a 3-month caloric restriction diet compared to an active waiting group in 50 elderly persons overweight and with obesity. Peripheral insulin sensitivity and central insulin sensitivity of the mesolimbic reward circuitry predicted weight loss success and improvement after caloric restriction. This is the first longitudinal study showing an improvement in central insulin sensitivity in humans.
Strengths
The major strength of the paper is the longitudinal study design in persons at high risk to develop type 2 diabetes with multiple fMRI visits, with a state-of-the-art fMRI design. Moreover, the study uses a placebo-controlled approach to evaluate insulin sensitivity in the brain. Another strength is the fact the control group is an active …Joint Public Review:
Tiedemann et al. evaluated the neural response to insulin before and after a 3-month caloric restriction diet compared to an active waiting group in 50 elderly persons overweight and with obesity. Peripheral insulin sensitivity and central insulin sensitivity of the mesolimbic reward circuitry predicted weight loss success and improvement after caloric restriction. This is the first longitudinal study showing an improvement in central insulin sensitivity in humans.
Strengths
The major strength of the paper is the longitudinal study design in persons at high risk to develop type 2 diabetes with multiple fMRI visits, with a state-of-the-art fMRI design. Moreover, the study uses a placebo-controlled approach to evaluate insulin sensitivity in the brain. Another strength is the fact the control group is an active waiting group, which means that they received dietary counselling after the study and additionally benefited from the study by receiving training courses on stress management.Weakness
A weakness of the study is the lack of metabolic assessments of the participants. Only fasting blood samples were available. No oral glucose tolerance test or hyperinsulinemic-euglycemic clamps were acquired to quantify peripheral or whole-body insulin resistance. Whether peripheral insulin sensitivity and central insulin sensitivity are, in fact, independently involved in the success or treatment outcome of intervention still needs to be validated in future studies.
Another weakness is the food cue picture set implemented in the study. The different categories of pictures were not carefully matched for psychological and physical variables (such as the complexity of a picture). This could potentially influence neural food cue reactivity.
The study evaluated the regional BOLD response of the reward circuitry showing that insulin signaling in the VTA and nucleus accumbens play an important role in successful weight loss. The role of insulin signaling on projections (or connectivity) of the mesolimbic reward circuitry was not evaluated in the current study. -
