This pathway represents the different molecular interactions that may occur following the dis-regulation of signaling pathways in adipocyte differentiation and proliferation. That may result in the abnormal distribution of white adipose tissue, leading to the onset of lipodystrophic syndromes. This laminopathic pathway stems from mutations mainly occurring in the LMNA gene, and can be associated with the onset of other laminopathic syndromes due to a malfunction in the lamin A processing pathway. Other laminopathic diseases are associated with LMNA mutations, thus this pathway represents the overlapping interactions in such phenotypic diseases.
GLUT4- associated with noninsulin diabetes mellitus
glucose regulation and fatty acid oxidation metabolism --> is secreated from adipose tissue
targets HMGA2, decreasing it --> high amounts in mature adipocytes
c40
Wnt signaling inhibits protease complex to allow for beta catenin localisation into the nucleus and prevent its degredation
Wnt signaling functions as an adipogenic switch. When it is on, adipogenesis is repressed --> in first days of adipogenesis- differentiation is blocked
when it is off, adipogenesis is initiated.
when disrupted = spontaneous adipogenesis
In Wnt signaling absence, myoblasts are reprogrammed to the adipocyte lineage and undergo spontaneous differentiation.
is down regulated following overexpression of miR33B
ba8
activated in early stages of adipogenesis --> activates transcription of PPARG and CEBPA by binding to promoter region in later stages of adipogenesis as are anti mitotic- promote terminal differentiation
ba8
c5e
is down regulated following overexpression of miR33B
upregulation will stimulate wnt signaling to down regulate adipogenesis
c0c
Single point mutations = AD-EMD
bb2
intronic microRNA located within the genes encoding SREBP are transcribed in concert with their host genes and function alongside them to regulate cholesterol/FA and glucose metabolism
MIR33b is highly induced upon differentiation of human preadipocytes + SREBP1
inhibition of MiR-33b enhances lipid droplet accumilation + its overexpression impaired preadipocyte proliferation + PPARG activation --> may be mediated by targeting HMGA2/CDK6+ others
overexpression of miR-33b causes
reduced preadipocyte proliferation and impaired differentiation
e inhibition of miR-33b enhanced lipid accumulation in differentiating adipocytes
negative regulator of adipogenesis, despite being highly upregulated during
the later stages of adipocyte differentiation.
f89
bb2
Novel F388L mutation is associated with a form of partial lipodystrophy
d0e
ef3
LMNA heterozygous splicing mutation --> loss of exon 11 results in a truncated pre lamin A - removal of Carboxyl terminal motif - interaction with other proteins - disrupted function
can also result from ZMPSTE24 mutations - premature stop codon - no propper processing of lamin A - can also result from null mutations
b8f
chromatin remodeling factor--> important role in the clonal-expansion phase of
adipogenesis - may be able to control critical genes involved in cellular proliferation--> loss of HMGA2 impairs adipocyte differentiation
overexpression of miR33B caused a significant reduction in HMGA2
HMGA2 is induced during the clonal-expansion phase of adipogenesis but
reduced following terminal differentiation
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b39
Mutations are linked to X-EMD
c37
e63
ebe
bed
Is down regulated following overexpression of MIR33B
f89
ec9
Wnt signaling promotes hMSC diffferentiation for osteogenesis
ebe
overexpression of miR33B causes downregulation of these molecules - influence adipocyte proliferation and differentation
f89
c7a
bed
activation of this complex allows for the activation of Wnt target genes
d86
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