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Obese men respond to cognitive but not to catabolic brain insulin signaling
Abstract
Context and objective Insulin acts in the brain to reduce food intake and body weight and is considered a major adiposity signal in energy homeostasis. In normal-weight men, intranasal insulin administration reduces body fat and improves declarative memory. The present experiments aimed to generalize these findings to obese patients, with a view to evaluate the therapeutic potential of the compound.Design, subjects and measurements Insulin and placebo, respectively, were intranasally administered four times a day (amounting to 160 IU day(-1)) over 8 weeks to two groups of 15 obese men each.Results Contrasting with the catabolic effects in normal-weight men, insulin treatment did not induce any significant reduction of body weight (P>0.50) and body fat (P>0.44) in the obese subjects. However, in accordance with the effects in normal-weight men, declarative memory and mood were improved (P<0.05) and hypothalamic-pituitary-adrenal axis activity as assessed by circulating ACTH (P<0.01) and cortisol levels (P<0.04) was reduced.Conclusions Our results indicate that in obese men, intranasal insulin is functionally active in the central nervous system but fails to affect the neuronal networks critically involved in body weight regulation. We conclude that obesity in men is associated with central nervous resistance to the adiposity signal insulin. This defect likely contributes to the persistence of obesity in spite of elevated levels of circulating insulin in obese patients.
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“8-week administration of IN insulin failed to affect body weight and fat mass in obese individuals.”
From Intranasal insulin (2021) · cites this paper as [87]
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“Signs of reduced hypothalamic-pituitary-adrenal (HPA) axis activity as a result of IN insulin were, however, also observed in human participants under resting conditions after 8 weeks of daily administration.”
From Intranasal insulin (2021) · cites this paper as [87]
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“This finding was later replicated in obese men.87”
From Intranasal insulin (2021) · cites this paper as [87]
In the citing paper
“The 8-week paradigm of IN insulin administration described above improved rated mood in normal-weight,38 as well as obese participants.87”
From Intranasal insulin (2021) · cites this paper as [87]
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Metadata
- Authors
- Hallschmid, M., Benedict, C., Schultes, B., Born, J., & Kern, W.
- Affiliations
- University of Lübeck (DE)
- Kantonsspital St. Gallen (CH)
- Corresponding author
- Hallschmid, M
- Venue
- International Journal of Obesity
- Published
- 2007-09-11
- Volume
- 32
- Issue
- 2
- Pages
- 275-282
- ISSN
- 0307-0565 (ISSN-L)
- 1476-5497
- OpenAlex
- W2015016479
- Cited by
- 165
- References
- 46
- Citations by year
- 2026: 5 · 2025: 4 · 2024: 4 · 2023: 14 · 2022: 6 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 11 · 2017: 14 · 2016: 9 · 2015: 9 · 2014: 10 · 2013: 13 · 2012: 8
- FWCI
- 2.99
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- International Journal of Obesity (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
- Keywords
- intranasal insulin, obesity, brain insulin signaling, declarative memory, hypothalamic-pituitary-adrenal axis, ACTH, cortisol, body weight regulation, energy homeostasis, sex differences
- MeSH terms
- Adipose Tissue, Administration, Intranasal, Adult, Affect, Body Weight, Brain, Cognition, Humans, Hypoglycemic Agents, Insulin, Male, Memory, Obesity, Treatment Outcome, Body Size
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