Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat 
Appetite in Obese Rats

Hankir, MK; Seyfried, F; Hintschich, CA; Diep, T-A; Kleberg, K; Kranz, M; Deuther-Conrad, W; Tellez, LA; Rullmann, M; Patt, M; Teichert, J; Hesse, S; Sabri, O; Brust, P; Hansen, HS; de Araujo, IE; Krügel, U; Fenske, WK

doi:10.1016/j.cmet.2016.12.006

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Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats

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https://www.sciencedirect.com/science/article/pii/S1550413116306398
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Citation

Hankir, M., Seyfried, F., Hintschich, C., Diep, T.-A., Kleberg, K., Kranz, M., et al. (2017). Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats. Cell Metabolism, 25(2), 335-344. doi:10.1016/j.cmet.2016.12.006.

Cite as: https://hdl.handle.net/21.11116/0000-000D-5BF4-A

Abstract

Bariatric surgery remains the single most effective long-term treatment modality for morbid obesity, achieved mainly by lowering caloric intake through as yet ill-defined mechanisms. Here we show in rats that Roux-en-Y gastric bypass (RYGB)-like rerouting of ingested fat mobilizes lower small intestine production of the fat-satiety molecule oleoylethanolamide (OEA). This was associated with vagus nerve-driven increases in dorsal striatal dopamine release. We also demonstrate that RYGB upregulates striatal dopamine 1 receptor (D1R) expression specifically under high-fat diet feeding conditions. Mechanistically, interfering with local OEA, vagal, and dorsal striatal D1R signaling negated the beneficial effects of RYGB on fat intake and preferences. These findings delineate a molecular/systems pathway through which bariatric surgery improves feeding behavior and may aid in the development of novel weight loss strategies that similarly modify brain reward circuits compromised in obesity.