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Tracing from Fat Tissue, Liver, and Pancreas: A Neuroanatomical Framework for the Role of the Brain in Type 2 Diabetes

Netherlands Institute for Brain Research (F.K., Y.S.K., C.v.H., J.v.d.V., A.K., R.M.B.), 1105 AZ Amsterdam, The Netherlands; Department of Endocrinology and andMetabolism (F.K., H.P.S., E.F.), Academic Medical Center, University of Amsterdam, 1100 DD Amsterdam, The Netherlands; Department of Endocrinology and Metabolism (F.K., J.A.R.), Leiden University Medical Center, 2300 RC Leiden, The Netherlands; and Friedrich-Loeffler-Institute (T.C.M.), Federal Research Institute for Animal Health, D-17493 Insel Riems, Germany

Address all correspondence and requests for reprints to: Felix Kreier, Netherlands Institute for Brain Research, Meibergdreef 33, 1105 AZ Amsterdam, The Netherlands. E-mail: f.kreier{at}nih.knaw.nl.

The hypothalamus uses hormones and the autonomic nervous system to balance energy fluxes in the body. Here we show that the autonomic nervous system has a distinct organization in different body compartments. The same neurons control intraabdominal organs (intraabdominal fat, liver, and pancreas), whereas sc adipose tissue located outside the abdominal compartment receives input from another set of autonomic neurons. This differentiation persists up to preautonomic neurons in the hypothalamus, including the biological clock, that have a distinct organization depending on the body compartment they command. Moreover, we demonstrate a neuronal feedback from adipose tissue that reaches the brainstem. We propose that this compartment-specific organization offers a neuroanatomical perspective for the regional malfunction of organs in type 2 diabetes, where increased insulin secretion by the pancreas and disturbed glucose metabolism in the liver coincide with an augmented metabolic activity of visceral compared with sc adipose tissue.

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