A Potential Role for the Midbrain in Integrating Fat-Free Mass Determined Energy Needs: An H215O PET Study

Little is known on how sensing of energy needs is centrally represented, integrated, and translated into the behavioral aspects of energy homeostasis. Fat free mass (FFM) is the major determinant of energy expenditure. We investigated how interindividual variances in FFM relate to neuronal activity in humans. Healthy adults (n=64, 21F/43M; age 31.3 +/- 9.1y; percentage of body fat [PFAT] 25.6 +/- 10.7%; BMI 30.4 +/- 9) underwent a 36h fast and subsequent (H2O)-O-15 positron emission tomographic (PET) measurement of regional cerebral blood flow (rCBF). Multiple variable regression analysis revealed significant associations of FFM with rCBF within the midbrain [including parts of the periaqueductal gray (PAG), ventral tegmental area (VTA), thalamic and hypothalamic regions], the bilateral parahippocampal region, left anterior cingulate, left insular cortex, right cerebellum, and distinct regions within the temporal and occipital cortex. In contrast, no significant associations were found for fat mass (FM). We investigated the potential functional-anatomical link between FFM and central regulation of food intake by performing a conjunction analysis of FFM and the perceived hunger feelings. This showed a significant overlap within the midbrain PAG. Mediation analysis demonstrated a significant indirect effect of FFM on hunger with PAG rCBF as mediator. Most regions we found to be associated with FFM form part in ascending homeostatic pathways and cortical circuitries implicated in the regulation of basic bodily functions indicating a potential role of these central networks in the integration of FFM determined energy needs. Hum Brain Mapp 36:2406-2415, 2015. (c) 2015 Wiley Periodicals, Inc.