TY - JOUR
T1 - Metabolic and hormonal signatures in pre-manifest and manifest Huntington's disease patients
AU - Wang, Rui
AU - Ross, Christopher A.
AU - Cai, Huan
AU - Cong, Wei Na
AU - Daimon, Caitlin M.
AU - Carlson, Olga D.
AU - Egan, Josephine M.
AU - Siddiqui, Sana
AU - Maudsley, Stuart
AU - Martin, Bronwen
PY - 2014
Y1 - 2014
N2 - Huntington's disease (HD) is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG) expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be "pre-manifest." Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids, and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon, and amylin were also observed. Total cholesterol, HDL-C, and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.
AB - Huntington's disease (HD) is an inherited neurodegenerative disorder typified by involuntary body movements, and psychiatric and cognitive abnormalities. Many HD patients also exhibit metabolic changes including progressive weight loss and appetite dysfunction. Here we have investigated metabolic function in pre-manifest and manifest HD subjects to establish an HD subject metabolic hormonal plasma signature. Individuals at risk for HD who have had predictive genetic testing showing the cytosine-adenine-guanine (CAG) expansion causative of HD, but who do not yet present signs and symptoms sufficient for the diagnosis of manifest HD are said to be "pre-manifest." Pre-manifest and manifest HD patients, as well as both familial and non-familial controls, were evaluated for multiple peripheral metabolism signals including circulating levels of hormones, growth factors, lipids, and cytokines. Both pre-manifest and manifest HD subjects exhibited significantly reduced levels of circulating growth factors, including growth hormone and prolactin. HD-related changes in the levels of metabolic hormones such as ghrelin, glucagon, and amylin were also observed. Total cholesterol, HDL-C, and LDL-C were significantly decreased in HD subjects. C-reactive protein was significantly elevated in pre-manifest HD subjects. The observation of metabolic alterations, even in subjects considered to be in the pre-manifest stage of HD, suggests that in addition, and prior, to overt neuronal damage, HD affects metabolic hormone secretion and energy regulation, which may shed light on pathogenesis, and provide opportunities for biomarker development.
KW - Huntington's disease
KW - lipids
KW - metabolic hormones
KW - peripheral energy metabolism
KW - pre-manifest
UR - http://www.scopus.com/inward/record.url?scp=84904393173&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84904393173&partnerID=8YFLogxK
U2 - 10.3389/fphys.2014.00231
DO - 10.3389/fphys.2014.00231
M3 - Article
C2 - 25002850
AN - SCOPUS:84904393173
SN - 1664-042X
VL - 5 JUN
JO - Frontiers in Physiology
JF - Frontiers in Physiology
M1 - Article 231
ER -