BACKGROUND: Obesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight. OBJECTIVE: To investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO). DESIGN: This was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO). RESULTS: A total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (P<0.05). CONCLUSION: No differences in fasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood-brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.
BACKGROUND:Obesity following hypothalamic damage is often severe and resistant to lifestyle changes. Disruption of hypothalamic feedback mechanisms that maintain energy homeostasis may be responsible for this intractable obesity. Adipocytokines including insulin and leptin are also known to be important regulators of appetite and weight. OBJECTIVE: To investigate the role of insulin, leptin, adiponectin and resistin in the aetiology of hypothalamic obesity (HO). DESIGN: This was a cross-sectional study of three groups of children, those with HO, congenital hypopituitarism (CH) and simple obesity (SO). RESULTS: A total of 69 children (HO=28, CH=18, SO=23) had leptin, resistin, adiponectin and insulin measured. Although fasting hyperinsulinaemia and insulin resistance were demonstrated, no differences in insulin or insulin resistance were seen between the groups. The HO group, however, had higher levels of leptin, adiponectin and resistin, which persisted even after adjusting for fat mass, compared with the other groups (P<0.05). CONCLUSION: No differences in fasting hyperinsulinaemia or insulin resistance were seen between the groups; however, leptin levels are elevated, even after adjusting for fat mass, suggesting that an element of leptin resistance is associated with HO. This is consistent with the inability of leptin to act on the hypothalamus, either due to transport across the blood-brain barrier or dysfunctional receptors. The lack of response to leptin may be more important in the development of obesity in these individuals, and the fasting hyperinsulinaemia is a result of the increased adipose tissue rather than the cause of the weight gain.
Authors: Valerie McLaughlin Crabtree; Kimberly Lauren Klages; April Sykes; Merrill S Wise; Zhaohua Lu; Daniel Indelicato; Thomas E Merchant; Yvonne Avent; Belinda N Mandrell Journal: J Clin Sleep Med Date: 2019-10-15 Impact factor: 4.062
Authors: Yan Yan Chen; Jin Ping Wang; Ya Yun Jiang; Hui Li; Ying Hua Hu; Kok Onn Lee; Guang Wei Li Journal: PLoS One Date: 2015-06-05 Impact factor: 3.240
Authors: E Danielle Sims; William J Jennings; Brianna Empringham; Adam Fleming; Carol Portwine; Donna L Johnston; Shayna M Zelcer; Shahrad Rod Rassekh; Sarah Burrow; Lehana Thabane; M Constantine Samaan Journal: Sci Rep Date: 2020-03-13 Impact factor: 4.379