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

Sewaybricker, Letícia Espósito; Schur, Ellen A.; Melhorn, Susan J.; Campos, Brunno M.; Askren, Mary K.; Nogueira, Guilherme; Zambon, Mariana Porto; Antônio, Maria Ângela R. G. M.; Cendes, Fernando; Velloso, Lı́cio A.; Guerra‐Júnior, Gil

doi:10.1111/ijpo.12486

Cited by 35 publications

(53 citation statements)

References 39 publications

(108 reference statements)

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“…Notably, adults with obesity, relative to those with healthy weight, have increased T2‐weighted signal intensity in the hypothalamus, indicative of gliosis (25). Likewise, in children with obesity, increased T2‐weighted signal intensity (suggesting hypothalamic gliosis) is positively associated with adiposity (30). Moreover, histological studies specifically examining hippocampal tissue have shown that different types of hippocampal tissue alterations can lead to either increased T2‐weighted signal intensity (i.e., hippocampal sclerosis and gliosis) or decreased T2‐weighted signal intensity (i.e., increased vacuolation) within this region (31,32).…”

Section: Introductionmentioning

confidence: 99%

Associations Between Body Weight, Hippocampal Volume, and Tissue Signal Intensity in 12‐ to 18‐Year‐Olds

Mestre

Bischoff‐Grethe

Wierenga

et al. 2020

Obesity

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Objective: The hippocampus is a key structure in feeding behaviors and weight regulation. Obesity may lead to disruptions in hippocampal structure. In animals, obesity-related factors (e.g., high-fat/sugar foods) are associated with hippocampal insult (e.g., alterations in the blood brain barrier). In humans, individuals with obesity, relative to healthy weight, have smaller hippocampal volumes. Few studies have examined the association between body weight and the hippocampus during adolescence, a critical brain development period. This study examined hippocampal volume and tissue signal intensity in adolescents across the weight spectrum. Methods: Structural magnetic resonance imaging and anthropomorphic data were available for 102 12-to 18-year-old adolescents (53% female; 15.07 [SD 1.84] years; standardized BMI [BMIz] scores using the Centers for Disease Control and Prevention growth charts: 0.54 [SD 1.17]) from the Pediatric Imaging, Neurocognition, and Genetics database. Linear regression models controlling for age, sex, genetic ancestry, scanner, and household income examined the relationship between BMIz, hippocampal volume, and T2-weighted hippocampal signal intensity. Results: BMIz was negatively associated with T2-weighted hippocampal signal intensity in the left (t = −3.05; P = 0.003; r = −0.21) and right (t = −2.50; P = 0.01; r = −0.36) hippocampi. BMIz was not significantly associated with hippocampal volume. Conclusions: BMIz is associated with hippocampal tissue characteristics during adolescence, which could impact later brain development.

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Section: Introductionmentioning

confidence: 99%

Associations Between Body Weight, Hippocampal Volume, and Tissue Signal Intensity in 12‐ to 18‐Year‐Olds

Mestre

Bischoff‐Grethe

Wierenga

et al. 2020

Obesity

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“…In addition, using functional magnetic resonance imaging (fMRI), obese individuals showed different hypothalamic functional activity compared with lean individuals after glucose consumption (Van De Sande‐Lee et al, 2011). Obese children were verified with hypothalamic gliosis, which was associated with alterations in the glucose‐stimulated hypothalamic functional response (Sewaybricker et al, 2019). After bariatric surgery, changes in hypothalamus activity after glucose intake were observed in fMRI analysis, bringing these responses closer to the lean group (Van De Sande‐Lee et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Acute physical exercise increases PI3K‐p110α protein content in the hypothalamus of obese mice

et al. 2020

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The anatomy of the hypothalamus includes many nuclei and a complex network of neurocircuits. In this context, some hypothalamic nuclei reside closer to the blood‐brain barrier, allowing communication with the peripheral organs through some molecules, such as leptin. Leptin is considered the main adipokine for energy homeostasis control. Furthermore, leptin signalling in the hypothalamus can communicate with insulin signalling through the activation of phosphoinositide 3‐kinase (PI3k). Previous data suggest that isoforms of PI3k are necessary to mediate insulin action in the hypothalamus. However, obese animals show impairment in the central signalling of these hormones. Thus, in the current study, we evaluated the role of acute exercise in the leptin and insulin pathways in the hypothalamus, as well as in food intake control in obese mice. Although acute physical exercise was not able to modulate leptin signalling, this protocol suppressed the increase in the suppressor of cytokine signalling 3 (SOCS3) protein levels. In addition, acute exercise increased the content of PI3k‐p110α protein in the hypothalamus. The exercised animals showed a strong tendency to reduction in cumulative food intake. For the first time, our results indicate physical exercise can increase PI3k‐p110α protein content in the hypothalamus of obese mice and regulate food intake.

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“…Besides adiposity, gliosis is another acquired factor that could potentially influence connectivity via effects on hypothalamic brain structure(17). Hypothalamic gliosis was first identified in diet-induced obese rodents in the arcuate nucleus of the MBH(17) and has been detected in humans by quantitative MRI methods in association with obesity in both adults(17,19,20) and children(22). MBH gliosis correlates positively with BMI(19) and visceral fat content(22).…”

Section: Discussionmentioning

confidence: 99%

“…Hypothalamic gliosis was first identified in diet-induced obese rodents in the arcuate nucleus of the MBH(17) and has been detected in humans by quantitative MRI methods in association with obesity in both adults(17,19,20) and children(22). MBH gliosis correlates positively with BMI(19) and visceral fat content(22). The data herein suggest that MBH gliosis, independent of obesity, might affect meal-related response in SN connectivity, but not necessarily basal connectivity.…”

Section: Discussionmentioning

confidence: 99%

Salience network connectivity is reduced by a meal and influenced by genetic background and hypothalamic gliosis

et al. 2019

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Background/Objectives:The salience network (SN) comprises brain regions that evaluate cues in the external environment in light of internal signals. We examined the SN response to meal intake and potential genetic and acquired influences on SN function.Subjects/Methods:Monozygotic (MZ; 40 pairs) and dizygotic (15 pairs) twins had body composition and plasma metabolic profile evaluated (glucose, insulin, leptin, ghrelin and GLP-1). Twins underwent resting-state functional magnetic resonance imaging (fMRI) scans before and after a standardized meal. The strength of SN connectivity was analyzed pre- and post-meal and the percentage change elicited by a meal was calculated. A multi-echo T2 MRI scan measured T2 relaxation time, a radiologic index of gliosis, in the mediobasal hypothalamus (MBH) and control regions. Statistical approaches included intraclass correlations (ICC) to investigate genetic influences and within-pair analyses to exclude genetic confounders.Results:SN connectivity was reduced by meal ingestion (β=−0.20; P<0.001). Inherited influences on both pre- and post-meal connectivity were present (ICC MZ twins 26%, P<0.05 and 47%, P<0.001, respectively), but not percentage change in response to the meal. SN connectivity in response to a meal did not differ between participants with obesity and of normal weight (χ2(1)=0.93; P=0.33). However, when participants were classified as having high or low signs of MBH gliosis, the high MBH gliosis group failed to reduce the connectivity in response to a meal (z=−1.32; P=0.19). Excluding genetic confounders, the percentage change in SN connectivity by a meal correlated to body fat percentage (r=0.24; P<0.01).Conclusions:SN connectivity was reduced by a meal, indicating potential participation of the SN in control of feeding. The strength of SN connectivity is inherited, but the degree to which SN connectivity is reduced by eating appears to be influenced by adiposity and the presence of hypothalamic gliosis.

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

Cited by 35 publications

References 39 publications

Associations Between Body Weight, Hippocampal Volume, and Tissue Signal Intensity in 12‐ to 18‐Year‐Olds

Associations Between Body Weight, Hippocampal Volume, and Tissue Signal Intensity in 12‐ to 18‐Year‐Olds

Acute physical exercise increases PI3K‐p110α protein content in the hypothalamus of obese mice

Salience network connectivity is reduced by a meal and influenced by genetic background and hypothalamic gliosis

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