Kreutzer, Carina, Peters, Soenke, Schulte, Dominik M., Fangmann, Daniela, Tuerk, Kathrin, Wolff, Stephan, van Eimeren, Thilo, Ahrens, Markus, Beckmann, Jan, Schafmayer, Clemens, Becker, Thomas, Kerby, Tina, Rohr, Axel, Riedel, Christian, Heinsen, Femke-Anouska, Degenhardt, Frauke, Franke, Andre ORCID: 0000-0003-1530-5811, Rosenstiel, Philip ORCID: 0000-0002-9692-8828, Zubek, Nana, Henning, Christian, Freitag-Wolf, Sandra, Dempfle, Astrid ORCID: 0000-0002-2618-3920, Psilopanagioti, Aristea, Petrou-Papadaki, Helen, Lenk, Lennart, Jansen, Olav, Schreiber, Stefan and Laudes, Matthias (2017). Hypothalamic Inflammation in Human Obesity Is Mediated by Environmental and Genetic Factors. Diabetes, 66 (9). S. 2407 - 2416. ALEXANDRIA: AMER DIABETES ASSOC. ISSN 1939-327X

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Abstract

Obesity is associated with hypothalamic inflammation (HI) in animal models. In the current study, we examined the mediobasal hypothalamus (MBH) of 57 obese human subjects and 54 age- and sex-matched nonobese control subjects by MRI and analyzed the T2 hyperintensity as a measure of HI. Obese subjects exhibited T2 hyperintensity in the left but not the right MBH, which was strongly associated with systemic low-grade inflammation. MRS revealed the number of neurons in the left hypothalamic region to be similar in obese versus control subjects, suggesting functional but not structural impairment due to the inflammatory process. To gain mechanistic insights, we performed nutritional analysis and 16S rDNA microbiome sequencing, which showed that high-fat diet induces reduction of Parasutterella sp. in the gut, which is significantly correlated with MBH T2 hyperintensity. In addition to these environmental factors, we found subjects carrying common polymorphisms in the JNK or the MC4R gene to be more susceptible to HI. Finally, in a subgroup analysis, bariatric surgery had no effect on MBH T2 hyperintensity despite inducing significant weight loss and improvement of peripheral insulin sensitivity. In conclusion, obesity in humans is associated with HI and disturbances in the gut-brain axis, which are influenced by both environmental and genetic factors.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Kreutzer, CarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peters, SoenkeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schulte, Dominik M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fangmann, DanielaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tuerk, KathrinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wolff, StephanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
van Eimeren, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ahrens, MarkusUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckmann, JanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schafmayer, ClemensUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Becker, ThomasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kerby, TinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rohr, AxelUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Riedel, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Heinsen, Femke-AnouskaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Degenhardt, FraukeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Franke, AndreUNSPECIFIEDorcid.org/0000-0003-1530-5811UNSPECIFIED
Rosenstiel, PhilipUNSPECIFIEDorcid.org/0000-0002-9692-8828UNSPECIFIED
Zubek, NanaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Henning, ChristianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Freitag-Wolf, SandraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dempfle, AstridUNSPECIFIEDorcid.org/0000-0002-2618-3920UNSPECIFIED
Psilopanagioti, AristeaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Petrou-Papadaki, HelenUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lenk, LennartUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jansen, OlavUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schreiber, StefanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Laudes, MatthiasUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-220674
DOI: 10.2337/db17-0067
Journal or Publication Title: Diabetes
Volume: 66
Number: 9
Page Range: S. 2407 - 2416
Date: 2017
Publisher: AMER DIABETES ASSOC
Place of Publication: ALEXANDRIA
ISSN: 1939-327X
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
GENOME-WIDE ASSOCIATION; GUT MICROBIOTA; INSULIN-RESISTANCE; RECEPTOR; ADIPOGENESIS; SPECTROSCOPY; CONSUMPTION; METABOLISM; DIVERSITY; GLIOSISMultiple languages
Endocrinology & MetabolismMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/22067

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