Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2021 Oct:123:154839.
doi: 10.1016/j.metabol.2021.154839. Epub 2021 Jul 29.

The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity

Katy A van Galen  1 , Jan Booij  2 , Anouk Schrantee  2 , Sofie M Adriaanse  2 , Unga A Unmehopa  1 , Eric Fliers  1 , Gary J Schwartz  3 , Ralph J DiLeone  4 , Kasper W Ter Horst  1 , Susanne E la Fleur  5 , Mireille J Serlie  6
Affiliations
Randomized Controlled Trial

The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity

Katy A van Galen et al. Metabolism. 2021 Oct.

Abstract

Background and aims: Serotonergic and dopaminergic systems in the brain are essential for homeostatic and reward-associated regulation of food intake and systemic energy metabolism. It is largely unknown how fasting influences these systems or if such effects are altered in humans with obesity. We therefore aimed to evaluate the effects of fasting on hypothalamic/thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability in lean subjects and subjects with obesity.

Methods: In this randomized controlled cross-over trial, we assessed the effects of 12 vs 24 h of fasting on SERT and DAT availability in the hypothalamus/thalamus and striatum, respectively, using SPECT imaging in 10 lean men and 10 men with obesity.

Results: As compared with the 12-h fast, a 24-h fast increased hypothalamic SERT availability in lean men, but not in men with obesity. We observed high inter-individual variation in the effects of fasting on thalamic SERT and striatal DAT, with no differences between lean men and those with obesity. In all subjects, fasting-induced increases in circulating free fatty acid (FFA) concentrations were associated with an increase in hypothalamic SERT availability and a decrease in striatal DAT availability. Multiple regression analysis showed that changes in plasma insulin and FFAs together accounted for 44% of the observed variation in striatal DAT availability.

Conclusion: Lean men respond to prolonged fasting by increasing hypothalamic SERT availability, whereas this response is absent in men with obesity. Inter-individual differences in the adaptations of the cerebral serotonergic and dopaminergic systems to fasting may, in part, be explained by changes in peripheral metabolic signals of fasting, including FFAs and insulin.

Keywords: Dopamine; Fasting; Food intake; Obesity; SPECT; Serotonin.

PubMed Disclaimer

Conflict of interest statement

Declaration of competing interest The authors declare that there is no conflict of interest associated with the manuscript.

Figures

Fig. 1.
Fig. 1.
Timeline of study protocol.
Fig. 2.
Fig. 2.
Representative T1w anatomical brain MRI scans overlaid with co-registered SPECT images and ROI masks. Striatal (red mask), hypothalamic (blue mask), and thalamic (green mask) uptake of the radiotracer 123I-FP-CIT.
Fig. 3.
Fig. 3.
Radiotracer binding after a 12-h vs 24-h fast in lean men and men with obesity. (A) Hypothalamic SERT availability. (B) Thalamic SERT availability. (C) Striatal DAT availability. Mean radiotracer binding after a 12-hand 24-h fast in lean men and men with obesity. (D) Hypothalamic SERT availability. (E) Thalamic SERT availability. (F) Striatal DAT availability. Data are individual subjects (A–C) and mean ± SD (D–F). One outlier was removed (A + D). *p < 0.05 for paired t-test **p < 0.05 for fasting-obesity interaction on repeated measures ANOVA.
Fig. 4.
Fig. 4.
Fasting-induced changes in circulating FFAs predict central SERT and DAT availability upon prolonged fasting in humans. Scatterplots showing the relationship between fasting-induced changes in plasma FFA levels and (A) hypothalamic SERT availability or (B) striatal DAT availability in all subjects. Data are lean (•) subjects or subjects with obesity (∘) (A–B). One outlier was removed (A).
Fig. 5.
Fig. 5.
Fasting-induced changes in plasma FFA and insulin together accounted for 44% of the variation in striatal DAT availability (adj. R2 = 0.441, p = 0.022). Partial regression plots showing the relationship between fasting-induced changes in striatal DAT availability and (A) plasma FFA levels, after adjusting for plasma insulin levels or (B) plasma insulin levels, after adjusting for plasma FFA levels. Data represent the subset of insulin-sensitive subjects (n = 13).
See this image and copyright information in PMC

References

    1. Organization, W.H. Factsheet: obesity and overweight; March 03, 2020.
    1. Swinburn BA, et al. The global obesity pandemic: shaped by global drivers and local environments. Lancet. 2011;378(9793):804–14. - PubMed
    1. Bluher M Obesity: global epidemiology and pathogenesis. Nat Rev Endocrinol. 2019;15(5):288–98. - PubMed
    1. Berthoud HR, Munzberg H, Morrison CD. Blaming the brain for obesity: integration of hedonic and homeostatic mechanisms. Gastroenterology. 2017;152(7):1728–38. - PMC - PubMed
    1. Schwartz MW, et al. Central nervous system control of food intake. Nature. 2000;404 (6778):661–71. - PubMed

Publication types

Substances