TY - JOUR
T1 - Obesity and diabetes in transgenic mice expressing proSAAS
AU - Wei, Suwen
AU - Feng, Yun
AU - Che, Fa Yun
AU - Pan, Hui
AU - Mzhavia, Nino
AU - Devi, Lakshmi A.
AU - McKinzie, Audra A.
AU - Levin, Nancy
AU - Richards, William G.
AU - Fricker, Lloyd D.
PY - 2004/3
Y1 - 2004/3
N2 - ProSAAS is a neuroendocrine peptide precursor that potently inhibits prohormone convertase 1 in vitro. To explore the function of proSAAS and its derived peptides, transgenic mice were created which express proSAAS using the beta-actin promoter. The body weight of transgenic mice was normal until approximately 10-12 weeks, and then increased 30-50% over wild-type littermates. Adult transgenic mice had a fat mass approximately twice that of wild-type mice, and fasting blood glucose levels were slightly elevated. In the pituitary, the levels of several fully processed peptides in transgenic mice were not reduced compared with wild-type mice, indicating that the proSAAS transgene did not affect prohormone convertase 1 activity in this tissue. Because the inhibitory potency of proSAAS-derived peptides towards prohormone convertase 1 is much greater in the absence of carboxypeptidase E activity, the proSAAS transgene was also expressed in carboxypeptidase E-deficient Cpefat/fat mice. Although the transgenic mice were born in the expected frequency, 21 of 22 proSAAS transgenic Cpefat/fat mice died between 11 and 26 weeks of age, presumably due to greatly elevated blood glucose. The levels of several pituitary peptides were significantly reduced in the proSAAS transgenic Cpefat/fat mice relative to non-transgenic Cpefat/fat mice, suggesting that the transgene inhibited prohormone convertase 1 in these mice. Taken together, these results are consistent with a role for proSAAS-derived peptides as neuropeptides that influence body weight independently of their function as inhibitors of prohormone convertase 1.
AB - ProSAAS is a neuroendocrine peptide precursor that potently inhibits prohormone convertase 1 in vitro. To explore the function of proSAAS and its derived peptides, transgenic mice were created which express proSAAS using the beta-actin promoter. The body weight of transgenic mice was normal until approximately 10-12 weeks, and then increased 30-50% over wild-type littermates. Adult transgenic mice had a fat mass approximately twice that of wild-type mice, and fasting blood glucose levels were slightly elevated. In the pituitary, the levels of several fully processed peptides in transgenic mice were not reduced compared with wild-type mice, indicating that the proSAAS transgene did not affect prohormone convertase 1 activity in this tissue. Because the inhibitory potency of proSAAS-derived peptides towards prohormone convertase 1 is much greater in the absence of carboxypeptidase E activity, the proSAAS transgene was also expressed in carboxypeptidase E-deficient Cpefat/fat mice. Although the transgenic mice were born in the expected frequency, 21 of 22 proSAAS transgenic Cpefat/fat mice died between 11 and 26 weeks of age, presumably due to greatly elevated blood glucose. The levels of several pituitary peptides were significantly reduced in the proSAAS transgenic Cpefat/fat mice relative to non-transgenic Cpefat/fat mice, suggesting that the transgene inhibited prohormone convertase 1 in these mice. Taken together, these results are consistent with a role for proSAAS-derived peptides as neuropeptides that influence body weight independently of their function as inhibitors of prohormone convertase 1.
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U2 - 10.1677/joe.0.1800357
DO - 10.1677/joe.0.1800357
M3 - Article
C2 - 15012590
AN - SCOPUS:11144355761
SN - 0022-0795
VL - 180
SP - 357
EP - 368
JO - Journal of Endocrinology
JF - Journal of Endocrinology
IS - 3
ER -