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

Mohammed K Hankir; Florian Seyfried; Constantin A Hintschich; Thi-Ai Diep; Karen Kleberg; Mathias Kranz; Winnie Deuther-Conrad; Luis A Tellez; Michael Rullmann; Marianne Patt; Jens Teichert; Swen Hesse; Osama Sabri; Peter Brust; Harald S Hansen; Ivan E de Araujo; Ute Krügel; Wiebke K Fenske

doi:10.1016/j.cmet.2016.12.006

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

Mohammed K Hankir, Florian Seyfried, Constantin A Hintschich, Thi-Ai Diep, Karen Kleberg, Mathias Kranz, Winnie Deuther-Conrad, Luis A Tellez, Michael Rullmann, Marianne Patt, Jens Teichert, Swen Hesse, Osama Sabri, Peter Brust, Harald S Hansen, Ivan E de Araujo, Ute Krügel, Wiebke K Fenske

62 Citationer (Scopus)

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.

Originalsprog	Engelsk
Tidsskrift	Cell Metabolism
Vol/bind	25
Udgave nummer	2
Sider (fra-til)	335-344
Antal sider	10
ISSN	1550-4131
DOI	https://doi.org/10.1016/j.cmet.2016.12.006
Status	Udgivet - 7 feb. 2017

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10.1016/j.cmet.2016.12.006

http://www.cell.com/article/S1550413116306398/pdf

Citationsformater

Hankir, M. K., Seyfried, F., Hintschich, C. A., Diep, T-A., Kleberg, K., Kranz, M., Deuther-Conrad, W., Tellez, L. A., Rullmann, M., Patt, M., Teichert, J., Hesse, S., Sabri, O., Brust, P., Hansen, H. S., de Araujo, I. E., Krügel, U., & Fenske, W. K. (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. https://doi.org/10.1016/j.cmet.2016.12.006

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 2017, 'Gastric Bypass Surgery Recruits a Gut PPAR-α-Striatal D1R Pathway to Reduce Fat Appetite in Obese Rats', Cell Metabolism, bind 25, nr. 2, s. 335-344. https://doi.org/10.1016/j.cmet.2016.12.006

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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.",

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AU - Hankir, Mohammed K

AU - Seyfried, Florian

AU - Hintschich, Constantin A

AU - Diep, Thi-Ai

AU - Kleberg, Karen

AU - Kranz, Mathias

AU - Deuther-Conrad, Winnie

AU - Tellez, Luis A

AU - Rullmann, Michael

AU - Patt, Marianne

AU - Teichert, Jens

AU - Hesse, Swen

AU - Sabri, Osama

AU - Brust, Peter

AU - Hansen, Harald S

AU - de Araujo, Ivan E

AU - Krügel, Ute

AU - Fenske, Wiebke K

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AB - 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.

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

Abstract

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