Reductions in Basal Metabolic Rate and Physical Activity Contribute to Hypothalamic Obesity

Shaikh, M Guftar; Grundy, Richard G.; Kirk, Jeremy

doi:10.1210/jc.2007-2672

Cited by 55 publications

(48 citation statements)

References 27 publications

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“…Maximal ability to utilize oxygen during exercise (VO 2 max ) depends on cardiac output, arterial oxygen content, and muscle oxygen extraction (31). In two recent studies, basal metabolic rate adjusted to total body weight was significantly lower in adult subjects with CP compared with controls (32), as well as in children with hypothalamic obesity (including CP) compared with simple obese controls (33). As basal metabolic rate is highly correlated with FFM and muscle mass, these findings could be in agreement with ours and suggest an alteration in muscle function, both at rest and during exercise.…”

Section: Discussionmentioning

confidence: 99%

Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement

Piguel¹,

Ábrahám²,

Bouhours‐Nouet³

et al. 2012

European Journal of Endocrinology

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Objective: Many patients treated for craniopharyngioma (CP) complain of a relative incapacity for physical activity. Whether this is due to an objective decrease in adaptation to exercise is unclear.We assessed exercise tolerance in children with surgically treated CP and appropriate pituitary hormone replacement therapy compared with healthy controls and we examined the potential relationships with hypothalamic involvement, GH replacement, and the catecholamine deficiency frequently observed in these subjects. Design and methods: Seventeen subjects (12 males and five females) with CP and 22 healthy controls (14 males and eight females) aged 15.3G2.5 years (7.3-18 years) underwent a standardized cycle ergometer test. Maximum aerobic capacity was expressed as the ratio of VO 2max to fat-free mass (VO 2max /FFM), a measure independent of age and fat mass in children. Results: VO 2max /FFM was 20% lower in children with CP compared with controls (P!0.05), even after adjustment for gender. Children with hypothalamic involvement (nZ10) had a higher percentage of fat mass (P!0.05) than those without hypothalamic involvement (nZ7) and lower VO 2max /FFM (P!0.05), whereas children without hypothalamic involvement had VO 2max /FFM close to that of controls (PO0.05). GH treatment was associated with a significant positive effect on aerobic capacity (P!0.05) only in the absence of hypothalamic involvement. No relationship was found between exercise capacity parameters and daily urine epinephrine excretion or epinephrine peak response to insulin-induced hypoglycemia. Conclusions: Children with CP have a decrease in aerobic capacity mainly related to hypothalamic involvement. The hypothalamic factors altering aerobic capacity remain to be determined.

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Section: Discussionmentioning

confidence: 99%

Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement

Piguel¹,

Ábrahám²,

Bouhours‐Nouet³

et al. 2012

European Journal of Endocrinology

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“…Although it is not clear whether hypothalamic obesity occurs as a result of decreased energy expenditure or increased energy intake, recent studies have demonstrated that a decreased basal metabolic rate and lack of physical activity contribute to the development of overweight and obesity [42, 43]. A previous study showed that cranial irradiation induces hypothalamic obesity in a dose-dependent manner and is associated with insulin hypersecretion in the developing brain [44].…”

Section: Discussionmentioning

confidence: 99%

Cranial Irradiation Induces Hypothalamic Injury and Late-Onset Metabolic Disturbances in Juvenile Female Rats

Sun

Zhou

et al. 2018

Dev Neurosci

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Cranial radiotherapy is one of the most effective tools for treating children with brain tumors. However, radiotherapy-induced late-onset side effects have a significant impact on patients’ quality of life. The purpose of this study was to investigate the effects of irradiation on metabolism and the possible molecular and cellular mechanisms behind such effects. Female Wistar rats were subjected to a single dose of 6-Gy whole-brain irradiation on postnatal day 11. The animals were sacrificed 6 h or 20 weeks after irradiation. Cell death and proliferation, microglial activation, and inflammation were analyzed and RNA sequencing was performed. We found that irradiation led to a significantly increased body weight from 15 weeks (p < 0.05) along with white adipose tissue accumulation and adipocyte hypertrophy at 20 weeks, and these changes were accompanied by glucose and lipid metabolic disturbances as indicated by reduced glucose tolerance, increased insulin resistance, increased serum triglycerides, and an increased leptin/adiponectin ratio. Furthermore, irradiation induced cell death, microglial activation, inflammation, and persistent astrocyte reactivity in the hypothalamus. Hypothalamic transcriptome analysis showed that 865 genes were downregulated and 290 genes were upregulated in the irradiated group 20 weeks after irradiation, and further pathway analysis showed that the insulin resistance-related PI3K-Akt signaling pathway and the energy expenditure-related adipocytokine signaling pathway were downregulated. Gene Ontology enrichment analysis showed that the expression of fatty acid metabolism-related proteins and effector proteins was significantly different in the irradiation group. This study demonstrates that ionizing radiation to the juvenile female brain induces hypothalamic damage that is likely to be associated with delayed metabolic abnormalities, and this critical vulnerability of the hypothalamus to irradiation should be taken into consideration in the development of future protective strategies for radiotherapy.

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“…Host metabolic factors such as reduced energy expenditure [37], increased fat mass, [38], increased insulin resistance and hyperinsulinemia [39], and metabolic syndrome [39] may also be responsible for this late-onset variability and increase in BMI in groups 2 and 3.…”

Section: Discussionmentioning

confidence: 99%

Longitudinal Changes in Body Mass Index in Children with Craniopharyngioma

et al. 2014

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Objective: We investigated the relationship of body mass index at presentation and pituitary status with long-term changes in BMI over a period of 5 years. Study Design: Craniopharyngioma patients (n = 25) attending a tertiary pediatric endocrine center were divided into three groups based on their BMI at presentation [BMI ≥2 standard deviation scores (SDS), 0-1.99 SDS, and <0 SDS) and then analyzed for trends of BMI over a period of up to 5 years. Results: Median (interquartile range) BMI SDS and hypopituitarism at presentation versus at the 5-year follow-up were as follows: BMI SDS ≥2 group (n = 10): 3.55 (0.68), 6/10 versus 3.76 (1.13), 8/10; BMI SDS 0-1.99 group (n = 11): 1.68 (1.05), 3/11 versus 1.64 (2.04), 7/11, and BMI SDS <0 group (n = 4): -0.23 (0.93), 2/4 versus 0.61, 4/4. At the 5-year follow-up, 10/10, 7/11, and 1/4 subjects when divided in groups according to BMI at presentation were obese. Conclusions: Our data indicate that obesity at presentation, rather than panhypopituitarism either at or after presentation, predicts obesity 5 years after diagnosis. However, obesity at presentation is not always associated with the subsequent development of panhypopituitarism. Pediatric craniopharyngioma subjects who have BMI SDS ≥2 at presentation require early and aggressive intervention to help prevent the complications of obesity.

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Reductions in Basal Metabolic Rate and Physical Activity Contribute to Hypothalamic Obesity

Cited by 55 publications

References 27 publications

Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement

Impaired aerobic exercise adaptation in children and adolescents with craniopharyngioma is associated with hypothalamic involvement

Cranial Irradiation Induces Hypothalamic Injury and Late-Onset Metabolic Disturbances in Juvenile Female Rats

Longitudinal Changes in Body Mass Index in Children with Craniopharyngioma

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