Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0020473 (
hyperlipidemia
)
15,891
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
SEIPIN is an integral membrane protein located in the endoplasmic reticulum, regulating adipocytes differentiation and lipolysis. Deficiency of
Seipin
in mice causes severe general lipodystrophy, accompanied by insulin resistance, postprandial hypertriglyceridemia and steatohepatitis. In atherosclerosis-prone Ldlr null (Ldlr
-/-
) mice, lipodystrophy caused by
Seipin
deletion even led to severe hypercholesteremia and accelerated atherogenesis, when challenged with an atherogenic diet. However, whether the phenotypes observed in
Seipin
-/-
Ldlr
-/-
mice were a common consequence due to lipodystrophy, rather than genetic background restricted or diet dependent, was unknown. Herein we explored the lipodystrophy-related dyslipidemia, steatohepatitis and atherogenesis in another atherosclerosis-prone murine model, apolipoprotein E null (apoE
-/-
) mice. Besides, we also compared phenotypes between sexes in apoE
-/-
mice with
Seipin
deletion (
Seipin
-/-
apoE
-/-
). We found that compared with apoE
-/-
controls,
Seipin
-/-
apoE
-/-
mice also developed severe general lipodystrophy with
hyperlipidemia
, steatohepatitis and increased atherogenesis. Although the severity of adipose loss in female and male
Seipin
-/-
apoE
-/-
mice were similar,
hyperlipidemia
, steatohepatitis and atherosclerosis were less severe in females than in males. Therefore, we demonstrated that lipodystrophy-related metabolic disorders, caused by
Seipin
deletion, were independent of genetic background and experimental diet, as seen in Ldlr
-/-
and apoE
-/-
mice. However, gender factor affected the disease progression, with females more resistant to developing lipodystrophy-related metabolic consequences.
...
PMID:Dyslipidemia, steatohepatitis and atherogenesis in lipodystrophic apoE deficient mice with Seipin deletion. 2942 27
The protein arginine methyltransferase 5 (PRMT5) is an emerging regulator of cancer and stem cells including adipogenic progenitors. Here, a new physiological role of PRMT5 in adipocytes and systemic metabolism is reported. Conditional knockout mice were generated to ablate the
Prmt5
gene specifically in adipocytes (Prmt5
AKO
). The Prmt5
AKO
mice exhibit sex- and depot-dependent progressive lipodystrophy that is more pronounced in females and in visceral (than subcutaneous) white fat. The lipodystrophy and associated energy imbalance,
hyperlipidemia
, hepatic steatosis, glucose intolerance, and insulin resistance are exacerbated by high-fat-diet. Mechanistically, Prmt5 methylates and releases the transcription elongation factor SPT5 from Berardinelli-Seip congenital lipodystrophy 2 (
Bscl2
, encoding
Seipin
) promoter, and Prmt5
AKO
disrupts
Seipin
-mediated lipid droplet biogenesis. Prmt5 also methylates Sterol Regulatory Element-Binding Transcription Factor 1a (SREBP1a) and promotes lipogenic gene expression, and Prmt5
AKO
suppresses SREBP1a-dependent fatty acid metabolic pathways in adipocytes. Thus, PRMT5 plays a critical role in regulating lipid metabolism and lipid droplet biogenesis in adipocytes.
...
PMID:Protein Arginine Methyltransferase PRMT5 Regulates Fatty Acid Metabolism and Lipid Droplet Biogenesis in White Adipose Tissues. 3330 67
