Ghrelin in PWS and 'hypothalamic obesity'

Two recent papers look at the obesity due to hypothalamic damage (hypothalamic obesity-HO, which can occur, for example, after treatment for a brain tumor), and one directly compares that condition to PWS.

Based on these papers (abstract link below) it looks like the molecular basis for obesity due to HO is at least somewhat different than in PWS.
The authors found that unlike PWS, individuals with HO do not have elevated ghrelin levels. It's not entirely clear why this is, but an interesting possibility has to do with insulin. Normally, insulin negatively regulates ghrelin (so if you take in a lot of food, you release insulin and that causes ghrelin to go down so you'll stop eating). One potentially important difference between HO and PWS is that HO is associated with high insulin levels, whereas it has been noted that individuals with PWS have low levels of insulin (may be consistent with the observation that there is less diabetes than you might expect in the PWS population). So, low insulin may contribute to the high ghrelin levels found in individuals with PWS. Note that HO is not consistently associated with hyperphagia like PWS. All of this suggests that HO and PWS are not exactly the same in how they lead to obesity, but comparing the two groups to define what is the same and what is different can give important clues about the underlying causes of obesity in both populations.

-The insulin angle is very intriguing in light of the project Dr. Nicholls in undertaking (supported by FPWR funds, by the way : ) ). He has seen low insulin levels in his mouse model of PWS, which might be consistent with the finding of low insulin levels in patients with PWS.

-An additional finding in this study is that PYY3-36 (a gut hormone that signals satiety) secretion does not appear to be impaired in PWS.

Fasting ghrelin levels are not elevated in children with hypothalamic obesity. Kanumakala S, Greaves R, Pedreira C, Donath S, Warne G, Zacharin M, Harris M. J Clin Endocrinol Metab 90, 2691-2695, 2005

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. Goldstone AP, Patterson M, Kalingag N, Ghatei MA, Brynes AE, Bloom SR, Grossman AB, Korbonits M. J Clin Endocrinol Metab. 90:2681-90 2005

 

Topics: Research

Theresa Strong

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Theresa V. Strong, Ph.D., received a B.S. from Rutgers University and a Ph.D. in Medical Genetics from the University of Alabama at Birmingham (UAB). After postdoctoral studies with Dr. Francis Collins at the University of Michigan, she joined the UAB faculty, leading a research lab focused on gene therapy for cancer and directing UAB’s Vector Production Facility. Theresa is one of the founding members of FPWR and has directed FPWR’s grant program since its inception. In 2016, she transitioned to a full-time position as Director of Research Programs at FPWR. She remains an Adjunct Professor in the Department of Genetics at UAB. She and her husband Jim have four children, including a son with PWS.

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