Linked Life Data

21051554

Source:http://linkedlifedata.com/resource/pubmed/id/21051554

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-5-10
pubmed:abstractText
Congenital generalized lipodystrophy (CGL) comprises a heterogeneous group of rare diseases associated with partial or total loss of adipose tissue. Of these, autosomal recessive Berardinelli-Seip congenital lipodystrophy (BSCL) is characterized by the absence of metabolically active subcutaneous and visceral adipose tissues. Metabolic abnormalities associated with lipodystrophy include insulin resistance, hypertriglyceridemia, hepatic steatosis, and diabetes. One form of BSCL has been linked to genetic mutations affecting the lipid biosynthetic enzyme 1-acyl-sn-glycerol 3-phosphate O-acyltransferase 2 (AGPAT2), which is highly expressed in adipose tissue. Precisely how AGPAT2 deficiency causes lipodystrophy remains unresolved, but possible mechanisms include impaired lipogenesis (triglyceride synthesis and storage), blocked adipogenesis (differentiation of preadipocytes to adipocytes), or apoptosis/necrosis of adipocytes. Agpat2(-/-) mice share important pathophysiologic features of CGL previously reported in humans. However, the small white adipose tissue (WAT) depots consisting largely of amoeboid adipocytes with microvesiculated basophilic cytoplasm showed that adipogenesis with deficient lipogenesis was present in all usual locations. Although well-defined lobules of brown adipose tissue (BAT) were present, massive necrosis resulted in early ablation of BAT. Although necrotic or apoptotic adipocytes were not detected in WAT of 10-day-old Agpat2(-/-), the absence of adipocytes in aged mice indicates that these cells must undergo necrosis/apoptosis at some point. Another significant finding in aged lipodystrophic mice was massive pancreatic islet hypertrophy in the face of chronic hyperglycemia, which suggests that glucotoxicity is insufficient by itself to cause ?-cell loss and that adipocyte-derived factors help regulate total ?-cell mass.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1544-2217
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
48
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
642-54
pubmed:dateRevised
2011-11-17
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Pathology of congenital generalized lipodystrophy in Agpat2-/- mice.
pubmed:affiliation
Lexicon Pharmaceuticals, Inc, Pathology Department, The Woodlands, TX 77381-1160, USA. pvogel@lexpharma.com
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't