https://www.ncbi.nlm.nih.gov/pubmed/22879847
Alcohol, fork head
7 vastausta hakuun
Search results
Items: 7
1.
Westerhoff M, Tretiakova M, Hart J, Gwin K, Liu X, Zhou M, Yeh MM, Antic T.
Hum Pathol. 2014 May;45(5):1010-4. doi: 10.1016/j.humpath.2013.12.015.
FOXL2, a gene encoding a member of the fork-head-winged-helix
family of transcription factors, is one of the earliest expressed genes
during female gonadal development. It is expressed in normal ovarian
stroma and ovarian neoplasms with granulosa cell lineage. Nonovarian
tumors such as pancreatic mucinous cystic neoplasms (PMCs),
hepatobiliary cystadenomas (HBCs), and mixed epithelial and stromal
tumor of the kidney (MEST) have ovarian-type stroma. Immunohistochemical
staining with FOXL2, estrogen receptor, and progesterone receptor was
performed on 21 PMCs, 13 HBCs, and 10 MESTs and assessed for nuclear
immunohistochemical positivity in the tumor stroma. All cases of PMC and
HBC demonstrated nuclear reactivity for FOXL2 in the subepithelial
stromal cells. Ninety percent of MEST demonstrated nuclear FOXL2
positivity. Estrogen receptor nuclear positivity was demonstrated in 57%
of PMC, 77% of HBC, and 80% of MEST. Progesterone receptor nuclear
positivity was present in 67% of PMC, 100% of HBC, and 90% of MEST.
Clinical information was available for 37 patients. Seventy-eight
percent of the patients had a history of obesity, heavy alcohol
use, or hormone-related therapy. The 2 male patients had histories
significant for morbid obesity and chronic alcoholism. FOXL2 is
expressed from the early stages of ovarian development and has been
shown to be mandatory for normal ovarian function. We have shown that it
is also expressed in the aberrant ovarian-type stroma characteristic of
PMC, HBC, and MEST. Most of such patients, including the rare male
patients, have risk factors for hormonal abnormalities such as obesity
and hormonal replacement therapy.
Copyright © 2014 Elsevier Inc. All rights reserved.
KEYWORDS:
FOXL2; Hepatobiliary cystadenoma; Mixed epithelial and stromal tumor of the kidney; Ovarian-type stroma; Pancreatic mucinous cystic neoplasm
FOXL2; Hepatobiliary cystadenoma; Mixed epithelial and stromal tumor of the kidney; Ovarian-type stroma; Pancreatic mucinous cystic neoplasm
2.
Shen L, Liu Z, Gong J, Zhang L, Wang L, Magdalou J, Chen L, Wang H.
Toxicol Appl Pharmacol. 2014 Jan 15;274(2):263-73. doi: 10.1016/j.taap.2013.11.009.
Prenatal ethanol
exposure (PEE) induces dyslipidemia and hyperglycemia in fetus and
adult offspring. However, whether PEE increases the susceptibility to
non-alcoholic fatty liver disease (NAFLD) in offspring and its
underlying mechanism remain unknown. This study aimed to demonstrate an
increased susceptibility to high-fat diet (HFD)-induced NAFLD and its
intrauterine programming mechanisms in female rat offspring with PEE.
Rat model of intrauterine growth retardation (IUGR) was established by
PEE, the female fetus and adult offspring that fed normal diet (ND) or
HFD were sacrificed. The results showed that, in PEE+ND group, serum
corticosterone (CORT) slightly decreased and insulin-like growth
factor-1 (IGF-1) and glucose increased with partial catch-up growth; In
PEE+HFD group, serum CORT decreased, while serum IGF-1, glucose and
triglyceride (TG) increased, with notable catch-up growth, higher
metabolic status and NAFLD formation. Enhanced liver expression of the
IGF-1 pathway, gluconeogenesis, and lipid synthesis as well as reduced
expression of lipid output were accompanied in PEE+HFD group. In PEE
fetus, serum CORT increased while IGF-1 decreased, with low body weight,
hyperglycemia, and hepatocyte ultrastructural changes. Hepatic IGF-1
expression as well as lipid output was down-regulated, while lipid
synthesis significantly increased. Based on these findings, we propose a
"two-programming" hypothesis for an increased susceptibility to
HFD-induced NAFLD in female offspring of PEE. That is, the intrauterine
programming of liver glucose and lipid metabolic function is "the first
programming", and postnatal adaptive catch-up growth triggered by
intrauterine programming of GC-IGF1 axis acts as "the second
programming".
Copyright © 2013 Elsevier Inc. All rights reserved.
Key words
ACCα;
ACTB; ADIPOR2; AMPKα; APOB; CORT; CPT1α; Catch-up growth; FASN; FOXO1;
G6Pase; GAPDH; GC; GC–MS; GLUT2; GSK3β; Glucocorticoid–insulin-like
growth factor-1 axis; HFD; HMG-CoA reductase; HMGCR; HNF4; HPRT1; IGF-1;
IGF-1 receptor; IGF-1R; IGFBP3; INSR; IRS1; IRS2; IUGR; JAK2; Janus
kinase 2; LEPR; MS; MTTP; NAFLD; ND; Non-alcoholic fatty liver disease;
PEE; PPARα; Prenatal ethanol
exposure; SREBP1c; TG; Two-programming hypothesis; acetyl-CoA
carboxylase α; adenosine monophosphate activated protein kinase α;
adiponectin receptor 2; apolipoprotein B; carnitine palmitoyltransferase
1α; corticosterone; fatty acid synthase; fork-head
transcriptional factor O1; gas chromatography–mass spectrometry;
glucocorticoid; glucose transporter 2; glucose-6-phosphatase;
glyceraldehyde-phosphate dehydrogenase; glycogen synthase kinase 3β;
hepatocyte nuclear factor 4; high-fat diet; hypoxanthine
phosphoribosyltransferase 1; insulin receptor; insulin receptor
substrate 1; insulin receptor substrate 2; insulin-like growth factor
binding protein 3; insulin-like growth factor-1; intrauterine growth
retardation; leptin receptor; mTORC2; mammalian target of rapamycin
complex 2; metabolic syndrome; microsomal triglyceride transfer protein;
non-alcoholic fatty liver disease; normal diet; peroxisome proliferator
activated receptor α; prenatal ethanol exposure; sterol regulatory element binding protein-1c; triglyceride; β actin
3.
De Matteis R, Lucertini F, Guescini M, Polidori E, Zeppa S, Stocchi V, Cinti S, Cuppini R.
Nutr Metab Cardiovasc Dis. 2013 Jun;23(6):582-90. doi: 10.1016/j.numecd.2012.01.013.
Brown
adipose tissue (BAT) plays a major role in body energy expenditure
counteracting obesity and obesity-associated morbidities. BAT activity
is sustained by the sympathetic nervous system (SNS). Since a massive
activation of the SNS was described during physical activity, we
investigated the effect of endurance running training on BAT of young
rats to clarify the role of exercise training on the activity and
recruitment state of brown cells.
Male,
10-week-old Sprague Dawley rats were trained on a motor treadmill
(approximately 60% of VO2max), 5 days/week, both for 1 and 6 weeks. The
effect of endurance training was valuated using morphological and
molecular approaches. Running training affected on the morphology,
sympathetic tone and vascularization of BAT, independently of the
duration of the stimulus. Functionally, the weak increase in the
thermogenesis (no difference in UCP-1), the increased expression of
PGC-1α and the membrane localization of MCT-1 suggest a new function of
BAT. Visceral fat increased the expression of the FOXC2, 48 h after last
training session and some clusters of UCP-1 paucilocular and
multilocular adipocytes appeared.
Exercise seemed a weakly effective stimulus for BAT thermogenesis, but surprisingly, without the supposed metabolically hypoactive effects. The observed browning of the visceral fat, by a supposed white-to-brown transdifferentiation phenomena suggested that exercise could be a new physiological stimulus to counteract obesity by an adrenergic-regulated brown recruitment of adipocytes.
Exercise seemed a weakly effective stimulus for BAT thermogenesis, but surprisingly, without the supposed metabolically hypoactive effects. The observed browning of the visceral fat, by a supposed white-to-brown transdifferentiation phenomena suggested that exercise could be a new physiological stimulus to counteract obesity by an adrenergic-regulated brown recruitment of adipocytes.
Copyright © 2012 Elsevier B.V. All rights reserved.
4.
Grønning LM, Baillie GS, Cederberg A, Lynch MJ, Houslay MD, Enerbäck S, Taskén K.
FEBS Lett. 2006 Jul 24;580(17):4126-30.
Overexpression of forkhead transcription factor FOXC2 in white adipose
tissue (WAT) leads to a lean phenotype resistant to diet-induced
obesity. This is due, in part, to enhanced catecholamine-induced
cAMP-PKA signaling in FOXC2 transgenic mice. Here we show that rolipram
treatment of adipocytes from FOXC2 transgenic mice did not increase
isoproterenol-induced cAMP accumulation to the same extent as in wild
type cells. Accordingly, phosphodiesterase-4 (PDE4) activity was reduced
by 75% and PDE4A5 protein expression reduced by 30-50% in FOXC2
transgenic WAT compared to wild type. Thus, reduced PDE4 activity in
adipocytes from FOXC2 transgenic mice contributes to amplified beta-AR
induced cAMP responses observed in these cells.
- PMID:
- 16828089
6.
Yeon JE, Califano S, Xu J, Wands JR, De La Monte SM.
Hepatology. 2003 Sep;38(3):703-14.
Chronic ethanol consumption can cause sustained hepatocellular injury and inhibit the subsequent regenerative response. These effects of ethanol may be mediated by impaired hepatocyte survival mechanisms. The present study examines the effects of ethanol on survival signaling in the intact liver. Adult Long Evans rats were maintained on ethanol-containing
or isocaloric control liquid diets for 8 weeks, after which the livers
were harvested to measure mRNA levels, protein expression, and kinase or
phosphatase activity related to survival or proapoptosis mechanisms.
Chronic ethanol
exposure resulted in increased hepatocellular labeling for activated
caspase 3 and nuclear DNA damage as demonstrated using the TUNEL assay.
These effects of ethanol
were associated with reduced levels of tyrosyl phosphorylated (PY)
IRS-1 and PI3 kinase, Akt kinase, and Erk MAPK activities and increased
levels of phosphatase tensin homologue deleted on chromosome 10 (PTEN)
mRNA, protein, and phosphatase activity in liver tissue. In vitro
experiments demonstrated that ethanol
increases PTEN expression and function in hepatocytes. However,
analysis of signaling cascade pertinent to PTEN function revealed
increased levels of nuclear p53 and Fas receptor mRNA but without
corresponding increases in GSK-3 activity or activated BAD. Although fork-head transcription factor levels were increased in ethanol-exposed livers, virtually all of the fork-head protein detected by Western blot analysis was localized within the cytosolic fraction. In conclusion, chronic ethanol
exposure impairs survival mechanisms in the liver because of inhibition
of signaling through PI3 kinase and Akt and increased levels of PTEN.
However, uncoupling of the signaling cascade downstream of PTEN that
mediates apoptosis may account for the relatively modest degrees of
ongoing cell loss observed in livers of chronic ethanol-fed rats.
- PMID:
- 12939597
