TG synthesis impairment was also associated with downregulation of two important enzymes of this pathway: 1-acyl-sn-glycerol-3-phosphate acyltransferase 2 (AGPAT2
) and the phosphatidate phosphatase LPIN1 (lipin1) in BSCL2 knockdown during adipogenesis [11, 45].
Several responsible genes have been identified: 1-acylglycerol-3-phosphate O-acyltransferase 2 (AGPAT2
, CGL1) (3), Berardinelli-Seip congenital lipodystrophy 2 (BSCL2, CGL2) (4), caveolin 1 (CAV1, CGL3) (5), and polymerase I and transcript release factor (PTRF, CGL4) (6, 7).
Type 1 (AGPAT2
mutation) and type2 (BSCL2 mutation) have similar clinical features, but type 2 can be associated with mild intellectual disability.
This is one of the major regulators of adipogenesis that activates transcription of FABP4, ADIPOQ, and AGPAT2
Raffan et al., "Identification and characterisation of a novel pathogenic mutation in the human lipodystrophy gene AGPAT2
," in JIMD Reports--Case and Research Reports, 2012/6, vol.
The causal gene 'AGPAT2
' which is involved in the synthesis of phosphatidic acid and triglycerides, was removed in the mice-resulting in rodents with generalised lipodystrophy.
The causal gene, AGPAT2
, which is involved in the synthesis of phosphatidic acid and triglycerides, was removed in the mice, resulting in rodents with generalized lipodystrophy.
Such is the case in individuals with CGL, who have germ line transmission of mutations in genes such as 1acylglycerol 3-phosphate-O-acyltransferase 2 (AGPAT2
) , Berardinelli Seip congenital lipodystrophy 2 (BSCL2) , and Caveolin 1 (CAV1) 10].
Furthermore, the development of lipodystrophy is correlated with the mutations of several genes participating in adipose metabolism, such as peroxisome proliferator-activated receptor [gamma] (PPAR[gamma]), 1-acylglycerol-3-phosphate-O-acyltransferase2 (AGPAT2
), and Berardinelli-Seip congenital lipodystrophy (BSCL2), suggesting that this disease may be associated with adipocyte differentiation and lipid synthesis disorders in adipocytes .
We found a trend for more AGPAT1 transcripts in mammary tissues and a fivefold expression of AGPAT2
* In 2002, the mutated gene, AGPAT2
, linked to congenital generalized lipodystrophy, was identified.
CGL1 is caused by mutations in AGPAT2
. The AGPAT2
gene is located on chromosome 9q34 and encodes 1-acylglycerol-3-phosphate O-acyltransferase 2, which is involved in triglyceride biosynthesis (15).