Central 5-HT Neurotransmission Modulates Weight Loss following Gastric Bypass Surgery in Obese Individuals

Haahr, Mette E.; Hansen, Dorte L.; Fisher, Patrick M.; Svarer, Claus; Stenbæk, Dea Siggaard; Madsen, Karine; Madsen, Jacob; Holst, Jens J.; Baaré, William F.C.; Højgaard, Liselotte; Almdal, Thomas; Knudsen, Gitte M.

doi:10.1523/jneurosci.3348-14.2015

Cited by 39 publications

(42 citation statements)

References 30 publications

(16 reference statements)

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“…This is in accordance with other PET studies investigating monoamine transporters in cases of obesity [28]. Although the immediate effects on NA release or NA-associated network changes associated with feeding state prior to scanning cannot be excluded, we assume measuring transporters are insensitive to short-term fluctuations in neurotransmitter levels, as has been shown for the serotonin transporter [29].…”

Section: Discussionsupporting

confidence: 84%

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Hesse

Becker

Rullmann

et al. 2017

Eur J Nucl Med Mol Imaging

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Purpose The brain noradrenaline (NA) system plays an important role in the central nervous control of energy balance and is thus implicated in the pathogenesis of obesity. The specific processes modulated by this neurotransmitter which lead to obesity and overeating are still a matter of debate. Methods We tested the hypothesis that in vivo NA transporter (NAT) availability is changed in obesity by using positron emission tomography (PET) and S, S-[11C]O-methylreboxetine (MRB) in twenty subjects comprising ten highly obese (body mass index BMI > 35 kg/m2), metabolically healthy, non-depressed individuals and ten non-obese (BMI < 30 kg/m2) healthy controls. Results Overall, we found no significant differences in binding potential (BPND) values between obese and non-obese individuals in the investigated brain regions, including the NAT-rich thalamus (0.40 ± 0.14 vs. 0.41 ± 0.18; p = 0.84) though additional discriminant analysis correctly identified individual group affiliation based on regional BPND in all but one (control) case. Furthermore, inter-regional correlation analyses indicated different BPND patterns between both groups but this did not survive testing for multiple comparions. Conclusions Our data do not find an overall involvement of NAT changes in human obesity. However, preliminary secondary findings of distinct regional and associative patterns warrant further investigation.

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Section: Discussionsupporting

confidence: 84%

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Hesse

Becker

Rullmann

et al. 2017

Eur J Nucl Med Mol Imaging

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“…Bariatric surgery may uniquely target various anatomically and molecularly discrete brain feeding circuits (Haahr et al, 2015) at early and late time points postoperatively (Mumphrey et al, 2016). Thus, treatments which can mimic the dynamic neurochemical signature of RYGB might effectively improve feeding behavior in the long-term, causing and sustaining significant weight loss in obese individuals.…”

Section: Discussionmentioning

confidence: 99%

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

Hankir

Patt

et al. 2017

Front. Neurosci.

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Brain μ-opioid receptors (MORs) stimulate high-fat (HF) feeding and have been implicated in the distinct long term outcomes on body weight of bariatric surgery and dieting. Whether alterations in fat appetite specifically following these disparate weight loss interventions relate to changes in brain MOR signaling is unknown. To address this issue, diet-induced obese male rats underwent either Roux-en-Y gastric bypass (RYGB) or sham surgeries. Postoperatively, animals were placed on a two-choice diet consisting of low-fat (LF) and HF food and sham-operated rats were further split into ad libitum fed (Sham-LF/HF) and body weight-matched (Sham-BWM) to RYGB groups. An additional set of sham-operated rats always only on a LF diet (Sham-LF) served as lean controls, making four experimental groups in total. Corresponding to a stage of weight loss maintenance for RYGB rats, two-bottle fat preference tests in conjunction with small-animal positron emission tomography (PET) imaging studies with the selective MOR radioligand [11C]carfentanil were performed. Brains were subsequently collected and MOR protein levels in the hypothalamus, striatum, prefrontal cortex and orbitofrontal cortex were analyzed by Western Blot. We found that only the RYGB group presented with intervention-specific changes: having markedly suppressed intake and preference for high concentration fat emulsions, a widespread reduction in [11C]carfentanil binding potential (reflecting MOR availability) in various brain regions, and a downregulation of striatal and prefrontal MOR protein levels compared to the remaining groups. These findings suggest that the suppressed fat appetite caused by RYGB surgery is due to reduced brain MOR signaling, which may contribute to sustained weight loss unlike the case for dieting.

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“…The data used in our experiments are part of the clinical dataset detailed in [10]. High-resolution 3D T1-weighted MPRAGE of 21 individuals was acquired using a Siemens Magnetom Trio 3 T MR scanner at a voxel resolution of 1 mm 3 .…”

Section: Data Descriptionmentioning

confidence: 99%

Crowdsourcing for error detection in cortical surface delineations

et al. 2016

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Central 5-HT Neurotransmission Modulates Weight Loss following Gastric Bypass Surgery in Obese Individuals

Cited by 39 publications

References 30 publications

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Central noradrenaline transporter availability in highly obese, non-depressed individuals

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats

Crowdsourcing for error detection in cortical surface delineations

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