Functional MRI of the hypothalamic response to an oral glucose load

Abstract

Abbreviations ACTo the Editor: Functional MRI (fMRI) using a blood oxygen level dependent (BOLD) sequence provides a tool to measure the effects of alterations in blood glucose on the patterns and magnitudes of neuronal activation in the human brain [1]. Previous experiments using a glucose load have suggested that it is possible in humans to identify changes in the BOLD signal from areas within the hypothalamus [2-6]; however, the results have been contradictory. This study involved seven healthy participants aged 27-38 years (three female, four male; mean±SD BMI 23.6± 1.3 kg/m 2 ), who gave informed consent. The study was approved by the local research ethics committee. Each participant attended for two studies in random order: one involving ingestion of a glucose load and the other water.After anatomical scans and a 5 min baseline period of fMRI acquisition, participants were either given 75 g glucose diluted with 200 ml water or the same volume of water only. fMRI acquisition continued for a further 25 min after the start of drinking. Blood samples for measurement of plasma glucose were taken 5 min before the start of drinking and 25 min after the start of drinking. There was no difference in mean glucose levels between conditions at baseline, but significantly higher values in the glucose arm at the end of the study (4.41±0.31 mmol/l for the water arm vs 5.36± 0.28 mmol/l for the glucose arm, p00.001).With the use of a six-channel head coil at 1.5 T, fMRI variables were: repetition time04 s (three-shot echo planar imaging, volume acquisition in 12 s); echo time045 ms; 50 sagittal slices; 2 mm slice thickness; 0.2 mm interslice gap; 2×2 mm in-plane resolution. The 30 min fMRI measurement produced a sequence of 150 volume acquisitions, which were aligned to the 80th volume using SPM5 software (Wellcome Trust Centre for Neuroimaging, London, UK).The position of the hypothalamus was identified on a near-midline sagittal slice of the 80th fMRI volume acquisition on the basis of landmarks: the anterior commissure (AC), the optic chiasm (OC) and the mammillary body (MM). The MarsBaR toolbox for SPM5 (available from http://marsbar.sourceforge.net/) was used to specify the overall region of interest (ROI)-a parallelogram with three

Initial evidence for hypothalamic gliosis in children with obesity by quantitative T2 MRI and implications for blood oxygen‐level dependent response to glucose ingestion

“…This is consistent with a study including lean adolescents (N = 14) that demonstrated no change in hypothalamic perfusion after glucose ingestion; however, the same study reported increased perfusion in adolescents with obesity (N = 24) . In agreement with the latter, an increase in hypothalamic BOLD signal after glucose ingestion has also been described in a study with adults with obesity and lean subjects (total N = 21), and two studies involving only normal‐weight adults (N = 18 and 7, respectively). Such discrepancies in prior findings of hypothalamic response to glucose ingestion may be due to distinct fMRI methodologies to evaluate the hypothalamic function (BOLD, cerebral blood perfusion, and temporal cluster analyses); variability due to the small samples in these and the current study, and to the fact that the glucose stimulus triggers a complex peripheral and CNS response orchestrated by the hypothalamus .…”

Differential effects of hunger and satiety on insular cortex and hypothalamic functional connectivity

“…The hypothalamus plays a crucial role in food intake (Grill & Kaplan, ; Palkovits, ), and is extensively involved in homeostatic metabolic regulation (Carey et al ., ; Coll & Yeo, ; Zhou & Rui, ). Eating (Thomas et al ., ), and glucose (Matsuda et al ., ; Smeets et al ., , ; Flanagan et al ., ; Little et al ., ) or insulin administration (Kullmann et al ., ), exert significant suppressive effects on the blood oxygen level‐dependent (BOLD) signal within the hypothalamus. Additionally, the hypothalamus is physically connected to other areas involved in maintaining the homeostatic energy balance, and receives projections from the gastrointestinal tract via the brainstem (Blouet & Schwartz, ).…”

Is the Brain a Key Player in Glucose Regulation and Development of Type 2 Diabetes?

“…However, a brief summary is warranted given the intimate relationship between energy intake and glucose regulation. A decrease in neural activity following glucose and meal intake has been reported in the hypothalamus and elsewhere (Matsuda et al, 1999; Tataranni et al, 1999; Gautier et al, 2000; Liu et al, 2000; Smeets et al, 2005, 2007; Flanagan et al, 2012; Page et al, 2013) that differs in obesity and type 2 diabetes according to some studies (Matsuda et al, 1999; Gautier et al, 2000; Vidarsdottir et al, 2007). Moreover, studies employing task-based fMRI protocols have demonstrated activation of several CNS regions (in particular the orbitofrontal cortex, amygdala, hippocampus and insula) upon presenting the subject with visual food cues (LaBar et al, 2001; Killgore et al, 2003; St-Onge et al, 2005; Porubská et al, 2006; Führer et al, 2008) which was attenuated in the fed state in some studies (Baldo and Kelley, 2007; De Silva et al, 2011) and different in obesity or insulin resistance in others (Killgore and Yurgelun-Todd, 2005; Rothemund et al, 2007; Stoeckel et al, 2008; Martin et al, 2010; Wallner-Liebmann et al, 2010; Dimitropoulos et al, 2012; Heni et al, 2014a; Alsaadi and Van Vugt, 2015).…”