Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy

Chalfant, James S.; Smith, Mary Atkinson; Hu, Houchun H.; Dorey, Fred; Goodarzian, Fariba; Fu, Cecilia; Gilsanz, Vicente

doi:10.3945/ajcn.111.030650

Cited by 27 publications

(31 citation statements)

References 56 publications

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“…Recent studies have suggested evidence and biochemical links between BAT, WAT [35], and skeletal muscle recruitment and development [36–38]. Because BAT regulates thermogenesis [39] and energy expenditure, elucidating BAT associations with adiposity and muscle tone can lead to promising strategies aimed at facilitating the recruitment of brown adipocytes and in the preventive treatment of obesity during early stages of life.…”

Section: Discussionmentioning

confidence: 99%

Characterization of Human Brown Adipose Tissue by Chemical-Shift Water-Fat MRI

Hu¹,

Perkins²,

Chia³

et al. 2013

American Journal of Roentgenology

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OBJECTIVE The purpose of this study was to characterize human brown adipose tissue (BAT) with chemical-shift water-fat MRI and to determine whether trends and differences in fat-signal fractions and T2* relaxation times between BAT and white adipose tissue (WAT) are consistently observed postmortem and in vivo in infants, adolescents, and adults. MATERIALS AND METHODS A postmortem body and eight patients were studied. A six-echo spoiled gradient-echo chemical-shift water-fat MRI sequence was performed at 3 T to jointly quantify fat-signal fraction and T2* in interscapular-supraclavicular BAT and subcutaneous WAT. To confirm BAT identity, biopsy and histology served as the reference in the postmortem study and PET/CT was used in five of the eight patients who required examination for medical care. RESULTS Fat-signal fractions and T2* times were lower in BAT than in WAT in the postmortem example and in seven of eight patients. With the exception of one case, nominal comparisons between brown and white adipose tissues were statistically significant (p < 0.05). Between subjects, a large range of fat-signal fraction values was observed in BAT but not in WAT. CONCLUSION We have shown that fat-signal fractions and T2* values jointly derived from chemical-shift water-fat MRI are lower in BAT than in WAT likely because of differences in cellular structures, triglyceride content, and vascularization. The two metrics can serve as complementary biomarkers in the detection of BAT.

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Section: Discussionmentioning

confidence: 99%

Characterization of Human Brown Adipose Tissue by Chemical-Shift Water-Fat MRI

Hu¹,

Perkins²,

Chia³

et al. 2013

American Journal of Roentgenology

Self Cite

100

124

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“…Visualization of BAT in children is also dependent on disease status, weight, body composition, and the degree of sexual development (4, 18, 27, 28). Although excessive calorie intake has also been suggested to stimulate BAT activity in mice, whether diet induces BAT activation and thermogenesis in humans is the subject of considerable discussion (29).…”

Section: Recent Advances In Pediatric Bat Researchmentioning

confidence: 99%

“…The activation of BAT in children has been shown to be related to changes in weight and adiposity (28). Pediatric cancer patients with no visualization of BAT at diagnoses, but with evidence of BAT activity at follow-up PET/CT studies gained significantly less weight and subcutaneous and visceral adiposity than those who remained without BAT activity when disease-free.…”

Section: Recent Advances In Pediatric Bat Researchmentioning

confidence: 99%

Relevance of brown adipose tissue in infancy and adolescence

Gilsanz

Kajimura

2012

Pediatr Res

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Brown adipose tissue (BAT) was thought to disappear after infancy. Recent studies finding BAT in patients undergoing positron emission tomography/computed tomography (PET/CT) have renewed the interest in deciphering the relevance of this tissue in humans. Available data suggests that BAT is more prevalent in children than in adults, and that its activation during adolescence is associated to significantly less gains in weight and adiposity. Data also shows that pediatric patients with metabolically-active BAT on PET/CT examinations have significantly greater muscle volume than patients with no identifiable BAT. Both the activity and the amount of BAT increase during puberty. The magnitude of the increase is higher in boys when compared to girls, and closely related to gains in muscle volume. Hence, concurrent with the great gains in skeletal muscle during infancy and puberty, all infants and adolescents accumulate large amounts of BAT. These observations are consistent with in vitro investigations suggesting close interactions between brown adipocytes, white adipocytes, and myocites. In this review, we discuss the potential role of this tissue in regulating weight and musculoskeletal development in children.

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“…Therefore, it is possible that effects of early suboptimal nutrition to depress BAT activity in rodents could underlie increased risk of obesity observed in precocial species as well. In support of this idea, reduced BAT function in children is associated with increased obesity [135,136,137]. …”

Section: Introductionmentioning

confidence: 99%

“…The idea that increased fat deposition associated with catch-up growth [17,18] programs impaired BAT function is supported by the observation that malnourished toddlers that experience catch-up growth exhibit increased leptin and low FGF21 as compared to those who maintain a slow growth trajectory [156]. The early phase of BAT development is likely important, because failure to develop active BAT in children is correlated with increased BMI [135,136,137]. Thus, these observations are consistent with the hypothesis that increased fat deposition during rapid growth in infancy programs diminished BAT capacity and reduced ability to increase energy expenditure when confronted with a higher nutritional plane.…”

Section: Introductionmentioning

confidence: 99%

Developmental influences on circuits programming susceptibility to obesity

Zeltser

2015

Frontiers in Neuroendocrinology

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Suboptimal maternal nutrition exerts lasting impacts on obesity risk in offspring, but the direction of the effect is determined by the timing of exposure. While maternal undernutrition in early pregnancy is associated with increased body mass index, in later pregnancy it can be protective. The importance of the timing of maternal undernutrition is also observed in rodents, however, many of the processes that occur in the last trimester of human gestation are delayed to the postnatal period. Neonatal leptin administration exerts lasting impacts on susceptibility to obesity in rodents. Although leptin can influence the formation of hypothalamic circuits involved in homeostatic control of feeding during the postnatal period, these effects are too late to account for its ability to reverse adverse metabolic programming due to early gestational exposure to maternal undernutrition. This review presents an alternative framework for understanding the effects of neonatal leptin through influences on developing thermoregulatory circuits.

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Inverse association between brown adipose tissue activation and white adipose tissue accumulation in successfully treated pediatric malignancy

Abstract: The activation of BAT in pediatric patients undergoing treatment of malignancy is associated with significantly less adipose accumulation. This trial was registered at clinicaltrials.gov as NCT01517581.

Cited by 27 publications

References 56 publications

Characterization of Human Brown Adipose Tissue by Chemical-Shift Water-Fat MRI

Characterization of Human Brown Adipose Tissue by Chemical-Shift Water-Fat MRI

Relevance of brown adipose tissue in infancy and adolescence

Developmental influences on circuits programming susceptibility to obesity

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