본문 바로가기
KERD
논문KCI 등재

Pathophysiology and clinical characteristics of hypothalamic obesity in children and adolescents

최진호|김자혜
대한소아내분비학회 (Korean Society Of Pediatric Endocrinology)|2013.12|Annals of Pediatric Endocrinology & Metabolism|제18권 제4호|pp. 161-167

2

조회

0

다운로드

2

인용

0

참고문헌

키워드

ObesityLeptinInsulinHypothalamus
주제분류소아과학

초록

The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11β-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding,effective treatment for hypothalamic obesity has not yet been developed. Therefore,understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology,endocrine characteristics, and treatment strategies of hypothalamic obesity.

Abstract

The hypothalamus plays a key role in the regulation of body weight by balancing the intake of food, energy expenditure, and body fat stores, as evidenced by the fact that most monogenic syndromes of morbid obesity result from mutations in genes expressed in the hypothalamus. Hypothalamic obesity is a result of impairment in the hypothalamic regulatory centers of body weight and energy expenditure, and is caused by structural damage to the hypothalamus, radiotherapy, Prader-Willi syndrome, and mutations in the LEP, LEPR, POMC, MC4R and CART genes. The pathophysiology includes loss of sensitivity to afferent peripheral humoral signals, such as leptin, dysregulated insulin secretion, and impaired activity of the sympathetic nervous system. Dysregulation of 11β-hydroxysteroid dehydrogenase 1 activity and melatonin may also have a role in the development of hypothalamic obesity. Intervention of this complex entity requires simultaneous targeting of several mechanisms that are deranged in patients with hypothalamic obesity. Despite a great deal of theoretical understanding,effective treatment for hypothalamic obesity has not yet been developed. Therefore,understanding the mechanisms that control food intake and energy homeostasis and pathophysiology of hypothalamic obesity can be the cornerstone of the development of new treatments options. Early identification of patients at-risk can relieve the severity of weight gain by the provision of dietary and behavioral modification, and antiobesity medication. This review summarizes recent advances of the pathophysiology,endocrine characteristics, and treatment strategies of hypothalamic obesity.

참고문헌 (57)

  1. Daousi C, "Endocrine and neuroanatomic features associated with weight gain and obesity in adult patients with hypothalamic damage", Am J Med, 118, pp.45~50 (2005)
  2. Rutter MM, "Long-term endocrine sequelae of childhood cancer", Curr Opin Pediatr, 19, pp.480~487 (2007)
  3. Geffner M, "Changes in height, weight, and body mass index in children with craniopharyngioma after three years of growth hormone therapy: analysis of KIGS (Pfizer International Growth Database)", J Clin Endocrinol Metab, 89, pp.5435~5440 (2004)
  4. Deepak D, "Cardiovascular disease, hypertension, dyslipidaemia and obesity in patients with hypothalamic-pituitary disease", Postgrad Med J, 83, pp.277~280 (2007)
  5. Moraes JC, "High-fat diet induces apoptosis of hypothalamic neurons", PLoS One, 4, pp.e5045~ (2009)
  6. Hochberg I, "Hypothalamic obesity", Endocr Dev, 17, pp.185~196 (2010)
  7. Coll AP, "Proopiomelanocortin and energy balance: insights from human and murine genetics", J Clin Endocrinol Metab, 89, pp.2557~2562 (2004)
  8. Lu XY, "Interaction between alpha-melanocyte-stimulating hormone and corticotropinreleasing hormone in the regulation of feeding and hypothalamo-pituitary-adrenal responses", J Neurosci, 23, pp.7863~7872 (2003)
  9. Woods SC, "Central control of body weight and appetite", J Clin Endocrinol Metab, 93(11 Suppl 1), pp.S37~S50 (2008)
  10. Lustig RH, "Risk factors for the development of obesity in children surviving brain tumors", J Clin Endocrinol Metab, 88, pp.611~616 (2003)
  11. Muller HL, "Longitudinal study on growth and body mass index before and after diagnosis of childhood craniopharyngioma", J Clin Endocrinol Metab, 89, pp.3298~3305 (2004)
  12. Luque RM, "Impact of obesity on the growth hormone axis: evidence for a direct inhibitory effect of hyperinsulinemia on pituitary function", Endocrinology, 147, pp.2754~2763 (2006)
  13. Hochberg I, "Expanding the definition of hypothalamic obesity", Obes Rev, 11, pp.709~721 (2010)
  14. Beales PL, "New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey", J Med Genet, 36, pp.437~446 (1999)
  15. Bougneres P, "Endocrine manifestations of the rapid-onset obesity with hypoventilation, hypothalamic, autonomic dysregulation, and neural tumor syndrome in childhood", J Clin Endocrinol Metab, 93, pp.3971~3980 (2008)
  16. Haqq AM, "Serum ghrelin levels are inversely correlated with body mass index, age, and insulin concentrations in normal children and are markedly increased in Prader-Willi syndrome", J Clin Endocrinol Metab, 88, pp.174~178 (2003)
  17. Kanumakala S, "Fasting ghrelin levels are not elevated in children with hypothalamic obesity", J Clin Endocrinol Metab, 90, pp.2691~2695 (2005)
  18. Goldstone AP, "Fasting and postprandial hyperghrelinemia in Prader-Willi syndrome is partially explained by hypoinsulinemia, and is not due to peptide YY3-36 deficiency or seen in hypothalamic obesity due to craniopharyngioma", J Clin Endocrinol Metab, 90, pp.2681~2690 (2005)
  19. Hoybye C, "Peptides associated with hyperphagia in adults with Prader-Willi syndrome before and during GH treatment", Growth Horm IGF Res, 13, pp.322~327 (2003)
  20. Sahoo T, "Prader-Willi phenotype caused by paternal deficiency for the HBII-85 C", D box small nucleolar RNA cluster, 2008, pp.40, 719~721
  21. Zimmermann U, "Epidemiology, implications and mechanisms underlying drug-induced weight gain in psychiatric patients", J Psychiatr Res, 37, pp.193~220 (2003)
  22. Bergman RN, "Atypical antipsychotics and glucose homeostasis", J Clin Psychiatry, 66, pp.504~514 (2005)
  23. Gothelf D, "Weight gain associated with increased food intake and low habitual activity levels in male adolescent schizophrenic inpatients treated with olanzapine", Am J Psychiatry, 159, pp.1055~1057 (2002)
  24. Melkersson KI, "Elevated levels of insulin, leptin, and blood lipids in olanzapine-treated patients with schizophrenia or related psychoses", J Clin Psychiatry, 61, pp.742~749 (2000)
  25. Skorzewska A, "Abnormal foodseeking behavior after surgery for craniopharyngioma", Neuropsychobiology, 21, pp.17~20 (1989)
  26. Goldstone AP, "Prader-Willi syndrome: advances in genetics, pathophysiology and treatment", Trends Endocrinol Metab, 15, pp.12~20 (2004)
  27. Farooqi IS, "Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene", N Engl J Med, 348, pp.1085~1095 (2003)
  28. Dekkers OM, "Quality of life in treated adult craniopharyngioma patients", Eur J Endocrinol, 154, pp.483~489 (2006)
  29. Snow A, "Severe hypersomnolence after pituitary", hypothalamic surgery in adolescents: clinical characteristics and potential mechanisms, 2002, pp.110, e74~
  30. Bittel DC, "Prader-Willi syndrome: clinical genetics, cytogenetics and molecular biology", Expert Rev Mol Med, 7, pp.1~20 (2005)
  31. Shaikh MG, "Hyperleptinaemia rather than fasting hyperinsulinaemia is associated with obesity following hypothalamic damage in children", Eur J Endocrinol, 159, pp.791~797 (2008)
  32. Farooqi IS, "Leptin: a pivotal regulator of human energy homeostasis", Am J Clin Nutr, 89, pp.980S~984S (2009)
  33. Clément K, "A mutation in the human leptin receptor gene causes obesity and pituitary dysfunction", Nature, 392, pp.398~401 (1998)
  34. Guran T, "The role of leptin, soluble leptin receptor, resistin, and insulin secretory dynamics in the pathogenesis of hypothalamic obesity in children", Eur J Pediatr, 168, pp.1043~1048 (2009)
  35. Lustig RH, "Hypothalamic obesity caused by cranial insult in children: altered glucose and insulin dynamics and reversal by a somatostatin agonist", J Pediatr, 135(2 Pt 1), pp.162~168 (1999)
  36. Srinivasan S, "Features of the metabolic syndrome after childhood craniopharyngioma", J Clin Endocrinol Metab, 89, pp.81~86 (2004)
  37. Parton LE, "Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity", Nature, 449, pp.228~232 (2007)
  38. Phillip M, "Growth without growth hormone", J Pediatr Endocrinol Metab, 15(5), pp.1267~1272 (2002)
  39. Bucher H, "Insulin-like growth factors I and II, prolactin, and insulin in 19 growth hormone-deficient children with excessive, normal, or decreased longitudinal growth after operation for craniopharyngioma", N Engl J Med, 309, pp.1142~1146 (1983)
  40. Roth CL, "Reduced sympathetic metabolites in urine of obese patients with craniopharyngioma", Pediatr Res, 61, pp.496~501 (2007)
  41. Schofl C, "Sympathoadrenal counterregulation in patients with hypothalamic craniopharyngioma", J Clin Endocrinol Metab, 87, pp.624~629 (2002)
  42. Dun SL, "Cocaineand amphetamine-regulated transcript peptide and sympatho-adrenal axis", Peptides, 27, pp.1949~1955 (2006)
  43. Tiosano D, "11 beta-Hydroxysteroid dehydrogenase activity in hypothalamic obesity", J Clin Endocrinol Metab, 88, pp.379~384 (2003)
  44. Manley PE, "Sleep dysfunction in long term survivors of craniopharyngioma", J Neurooncol, 108, pp.543~549 (2012)
  45. Muller HL, "Melatonin secretion and increased daytime sleepiness in childhood craniopharyngioma patients", J Clin Endocrinol Metab, 87, pp.3993~3996 (2002)
  46. Mason PW, "The use of dextroamphetamine to treat obesity and hyperphagia in children treated for craniopharyngioma", Arch Pediatr Adolesc Med, 156, pp.887~892 (2002)
  47. Ismail D, "Dexamphetamine use for management of obesity and hypersomnolence following hypothalamic injury", J Pediatr Endocrinol Metab, 19, pp.129~134 (2006)
  48. Greenway FL, "Treatment of hypothalamic obesity with caffeine and ephedrine", Endocr Pract, 14, pp.697~703 (2008)
  49. Lustig RH, "Octreotide therapy of pediatric hypothalamic obesity: a double-blind, placebocontrolled trial", J Clin Endocrinol Metab, 88, pp.2586~2592 (2003)
  50. Cettour-Rose P, "Central stimulatory effect of leptin on T3 production is mediated by brown adipose tissue type II deiodinase", Am J Physiol Endocrinol Metab, 283, pp.E980~E987 (2002)
  51. Fernandes JK, "Triiodothyronine supplementation for hypothalamic obesity", Metabolism, 51, pp.1381~1383 (2002)
  52. Danielsson P, "Impact sibutramine therapy in children with hypothalamic obesity or obesity with aggravating syndromes", J Clin Endocrinol Metab, 92, pp.4101~4106 (2007)
  53. Drucker DJ, "The incretin system: glucagonlike peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors in type 2 diabetes", Lancet, 368, pp.1696~1705 (2006)
  54. Simmons JH, "Treatment with glucagon-like Peptide-1 agonist exendin-4 in a patient with hypothalamic obesity secondary to intracranial tumor", Horm Res Paediatr, 78, pp.54~58 (2012)
  55. Zoicas F, "GLP- 1 analogues as a new treatment option for hypothalamic obesity in adults: report of nine cases", Eur J Endocrinol, 168, pp.699~706 (2013)
  56. Muller HL, "First experiences with laparoscopic adjustable gastric banding (LAGB) in the treatment of patients with childhood craniopharyngioma and morbid obesity", Klin Padiatr, 219, pp.323~325 (2007)
  57. Inge TH, "Gastric bypass surgery for treatment of hypothalamic obesity after craniopharyngioma therapy", Nat Clin Pract Endocrinol Metab, 3, pp.606~609 (2007)

관련 논문AI추천

Genetic obesity: an update with emerging therapeutic approachesSohn Young Bae대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2022 · 제27권 제3호Prader-Willi syndrome: an update on obesity and endocrine problems조성윤, Jin Dong-Kyu, Kim Su Jin대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2021 · 제26권 제4호Leptin, Neuropeptide Y and Islet Amyloid Polypeptide Levels in Obese Children김은영, 최민선, Kyung Rae Moon, Soo Hee Jee대한소아소화기영양학회 · Pediatric Gastroenterology, Hepatology & Nutrition2012 · 제15권 제3호Issues in Infants with Prader-Will Syndrome: Special Review on Early Dietary Intervention and Early Use of Growth Hormone조성윤, 진동규대한소아내분비학회 · Annals of Pediatric Endocrinology & Metabolism2012 · 제17권 제3호Developmental programming of hypothalamic melanocortin circuitsBouret Sebastien G.생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권 Hypothalamic control of energy expenditure and thermogenesisKim Ki Woo, Kim Seul Ki, Kwon Obin, Lee Jin Sun, Park Sohee, Tran Le Trung생화학분자생물학회 · Experimental and Molecular Medicine2022 · 제54권

이 간행물의 다른 논문 (9건)

Reduced male fertility in childhood cancer survivors신충호, 이선희pp. 168-172Multicenter clinical trial of leuprolide acetate depot (Luphere depot 3.75 mg) for efficacy and safety in girls with central precocious puberty임중섭, 김유진, 이해상, 진동규, 김은영, 이영준, 김세영, Il Tae Hwang, 황진순pp. 173-178Changes of antithroglobulin antibody in children with congenital hypothyroidism김욱현, 최병호, 고철우, 조은미pp. 179-182Boys with precocious or early puberty: incidence of pathological brain magnetic resonance imaging findings and factors related to newly developed brain lesions최근희, 양세원, 윤주영, 정성준, 강민재, 신충호, 이영아, 이지은pp. 183-190The difference in serum alkaline phosphatase levels between girls with precocious puberty and those with normal puberty양수인, 임한혁, 좌혜정pp. 191-195
원문 보기