title: Lipodystrophy, Diabetes and Normal Serum Insulin in PPARγ-Deficient Neonatal Mice.
abstract: Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ. PPARγ-rescued placentas support development of PPARγ-deficient embryos that are viable and born in near normal numbers. However, PPARγ-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPARγ2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPARγ1 in the neonatal period either alone or in combination with PPARγ2 in lipid metabolism, glucose homeostasis and insulin sensitivity.
authors: Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors: Peter E
authors: PE
authors: O'Donnell
authors: Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors: Xiu Zhen
authors: XZ
authors: Ye
authors: Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors: Melissa A
authors: MA
authors: DeChellis
authors: Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors: Vannessa M
authors: VM
authors: Davis
authors: Department of Physiology, University of Michigan Medical School, Ann Arbor, MI, United States of America.
authors: Sheng Zhong
authors: SZ
authors: Duan
authors: Department of Physiology, University of Michigan Medical School, Ann Arbor, MI, United States of America.
authors: Richard M
authors: RM
authors: Mortensen
authors: Vascular Research Division, Department of Pathology, Brigham & Women's Hospital and Harvard Medical School, Boston, MA, United States of America.
authors: David S
authors: DS
authors: Milstone
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D003920:Diabetes Mellitus / Q000378:metabolism*; D005260:Female; D005855:Germ Layers / Q000378:metabolism; D006505:Hepatitis / Q000150:complications; D006529:Hepatomegaly / Q000150:complications; D006706:Homeostasis; D006949:Hyperlipidemias / Q000150:complications; D006951:Hyperlipoproteinemias / Q000150:complications; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007662:Ketosis / Q000150:complications; D008060:Lipodystrophy / Q000150:complications / Q000378:metabolism*; D051379:Mice; D009336:Necrosis; D047495:PPAR gamma / Q000172:deficiency*; D010920:Placenta / Q000378:metabolism; D011247:Pregnancy
chemical_list: D007328:Insulin; D047495:PPAR gamma