Hypothalamic Inflammation in Human Obesity Is Mediated by Environmental and Genetic Factors

• DOI: 10.2337/db17-0067
• Publication Date: 2017-06-03T00:20:14Z
• Authors: Carina Kreutzer; Sönke Peters; Dominik M. Schulte; Daniela Fangmann; Kathrin Türk; Stephan Wolff; Thilo van Eimeren; Markus Ahrens; Jan Beckmann; Clemens Schafmayer; Thomas Becker; Tina Kerby; Axel Rohr; Christian Riedel; Femke-Anouska Hei...; Frauke Degenhardt; Andre Franke; Philip Rosenstiel; Nana Zubek; Christian Henning; Sandra Freitag-Wolf; Astrid Dempfle; Aristea Psilopana...; Helen Petrou-Papa...; Lennart Lenk; Olav Jansen; Stefan Schreiber; Matthias Laudes
• Keywords: Genetic predisposition

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