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: EC:3.1.1.79 (
hormone-sensitive lipase
)
2,163
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Tyrosine hydroxylase (TH) catalyzes the first step in catecholamines synthesis. We studied the impact of reduced TH in brown adipose tissue (BAT) activation. In adult heterozygous (
Th
+/-
) mice, dopamine and noradrenaline (NA) content in BAT decreased after cold exposure. This reduced catecholaminergic response did not impair cold adaptation, because these mice induced uncoupling protein 1 (UCP-1) and maintained BAT temperature to a similar extent than controls (
Th
+/+
). Possible compensatory mechanisms implicated were studied.
Prdm16
and
Fgf21
expression, key genes in BAT activation, were elevated in
Th
+/-
mice at thermoneutrality from day 18.5 of embryonic life. Likewise, plasma FGF21 and liver
Fgf21
mRNA were increased. Analysis of endoplasmic reticulum (ER) stress, a process that triggers elevations in FGF21, showed higher phospho-IRE1, phospho-JNK, and
CHOP
in BAT of
Th
+/-
mice at thermoneutrality. Also, increased lipolysis in BAT of cold-exposure
Th
+/-
mice was demonstrated by increased phosphorylation of
hormone-sensitive lipase
(
HSL
), as well as diacylglycerol (DAG) and FFA content. Overall, these results indicate that the mild effects of
Th
haploinsufficiency on BAT function are likely due to compensatory mechanisms involving elevations in
Fgf21
and
Prdm16
and through adaptive changes in the lipid profile.
...
PMID:Increased FGF21 in brown adipose tissue of tyrosine hydroxylase heterozygous mice: implications for cold adaptation. 3035 54
Fatty acid-binding protein 4 (FABP4) is predominantly expressed in adipocytes and macrophages and regulates metabolic and inflammatory pathways. FABP4 is secreted from adipocytes during lipolysis, and elevated circulating FABP4 levels are associated with obesity, metabolic disease, and cardiac dysfunction. We previously reported that the bacterial respiratory pathogen
Chlamydia pneumoniae
infects murine adipocytes and exploits host FABP4 to mobilize fat and replicate within adipocytes. However, whether
C. pneumoniae
induces FABP4 secretion from adipocytes has not been determined. Here, we show that FABP4 is actively secreted by murine adipocytes upon
C. pneumoniae
infection. Chemical inhibition of lipase activity and genetic deficiency of
hormone-sensitive lipase
blocked FABP4 secretion from
C. pneumoniae
-infected adipocytes. Mechanistically,
C. pneumoniae
infection induced endoplasmic reticulum (ER) stress and the unfolded protein response (UPR), resulting in elevated levels of mitochondrial reactive oxygen species and cytosolic Ca
2+
Of note, exposure to a mitochondrial reactive oxygen species-specific scavenger, MitoTEMPO, reduced FABP4 release from
C. pneumoniae
-infected adipocytes. Furthermore, treatment with azoramide, which protects cells against ER stress, decreased FABP4 release from
C. pneumoniae
-infected adipocytes. Using gene silencing of
CHOP
(C/EBP homologous protein), a central regulator of ER stress, we further validated the role of
C. pneumoniae
infection-induced ER stress/UPR in promoting FABP4 secretion. Overall, these results indicate that
C. pneumoniae
infection robustly induces FABP4 secretion from adipocytes by stimulating ER stress/UPR. Our findings shed additional light on the etiological link between
C. pneumoniae
infection and metabolic syndrome.
...
PMID:
Chlamydia pneumoniae
infection-induced endoplasmic reticulum stress causes fatty acid-binding protein 4 secretion in murine adipocytes. 3199 97
