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Query: UMLS:C0036690 (
sepsis
)
59,461
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Fasting and
sepsis
induce profound changes in thyroid hormone (TH) central and peripheral metabolism. These changes affect TH action and are called the non-thyroidal illness syndrome (NTIS). To date, it is still debated whether NTIS represents an adaptive response or a real hypothyroid state at the tissue level. Moreover, even though it has been considered the same syndrome, we hypothesized that fasting and
sepsis
induce a distinct set of changes in thyroid hormone metabolism. Herein, we aimed to evaluate the central and peripheral expression of genes involved in the transport (MCT8/
Slc16a2
and
MCT10
/
Slc16a10
), metabolism (
Dio1, Dio2
, and
Dio3
) and action (
Thra
and
Thrb
) of TH during NTIS induced by fasting or
sepsis
. Male mice were subjected to a 48 h period of fasting or cecal ligation and puncture (CLP)-induced
sepsis
. At the peripheral level, fasting led to: (1) reduced serum thyroxine (T
4
) and triiodothyronine (T
3
), expression of
Dio1, Thra, Slc16a2
, and MCT8 protein in liver; (2) increased hepatic Slc16a10 and Dio3 expression; and (3) decreased
Slc16a2
and
Slc16a10
expressions in the thyroid gland. Fasting resulted in reduction of
Tshb
expression in the pituitary and increased expression of Dio2 in total hypothalamus, arcuate (ARC) and paraventricular (PVN) nucleus. CLP induced
sepsis
resulted in reduced: (1) T
4
serum levels; (2)
Dio1, Slc16a2, Slc16a10, Thra
, and
Thrb
expression in liver as well as
Slc16a2
expression in the thyroid gland (3)
Thrb
and
Tshb
mRNA expression in the pituitary; (4) total leukocyte counts in the bone marrow while increased its number in peritoneal and pleural fluids. In summary, fasting- or
sepsis
-driven NTIS promotes changes in the set point of hypothalamus-pituitary-thyroid axis through different mechanisms. Reduced hepatic THRs expression in conjunction with reduced TH transporters expression in the thyroid gland may indicate, respectively, reduction in the peripheral action and in the secretion of TH, which may contribute to the low TH serum levels observed in both models.
...
PMID:Differential Regulation of Thyroid Hormone Metabolism Target Genes during Non-thyroidal [corrected] Illness Syndrome Triggered by Fasting or Sepsis in Adult Mice. 2920 41
Background:
Sepsis
can cause the nonthyroidal illness syndrome (NTIS), resulting in perturbed thyroid hormone (TH) signaling and reduced thyroxine (T4) levels. TH is a major regulator of muscle function, via its influence on mitochondria. This study aimed at evaluating the relationship between TH signaling, mitochondrial function, and the antioxidant defense system in the diaphragms of septic mice.
Methods:
Male C57Bl/6 mice were divided into two groups: cecal ligation and puncture (CLP) and sham. Twenty-four hours after surgery, plasma, diaphragms, and livers were collected. TH metabolism and responses were analyzed by measuring messenger RNA (mRNA) expression of
Dio1
in the liver, and
Thra
,
Thrb
,
Dio
2,
Slc16a10
, and
Slc16a2
(encodes
MCT 10
and 8), in the diaphragm. T4 plasma levels were measured by radioimmunoassay. Damage to diaphragm mitochondria was assessed by electron microscopy and real-time polymerase chain reaction (qPCR), and function with oxygraphy. The diaphragm antioxidative defense system was examined by qPCR, analyzing superoxide dismutase (SOD) 1 (
Sod1
), mitochondrial superoxide dismutase (SOD 2;
Sod2
), extracellular superoxide dismutase (SOD 3;
Sod3
), glutathione peroxidase 1 (
Gpx1
), and catalase (
Cat
) expression. The effect of TH replacement was tested by treating the mice with T4 and triiodothyronine (T3) (CLP+TH) after surgery.
Results:
CLP mice presented reduced total plasma T4 concentrations, downregulated
Dio1
, and upregulated
Il1b
mRNA expression in the liver. CLP mice also displayed downregulated
Thra, Thrb, Slc16a10
, and
Slc16a2
expression in the diaphragm, suggesting that TH signaling was compromised. The expression of
Ppargc1a
(encoding PGC1a) was downregulated, which correlated with the decrease in the number of total mitochondria, increase in the percentage of injured mitochondria, downregulation of respiratory chain complex 2 and 3 mRNA expression, and reduced maximal respiration. In addition, septic animals presented a three-fold increase in
Ucp3
and
G6pdh
expression; downregulated
Sod3
,
Gpx1
, and
Cat
expression; and upregulated
Sod2
expression, potentially due to elevated reactive oxygen species levels. The mitochondrial number and the percentage of injured mitochondrial were similar between sham and CLP+TH mice.
Conclusions:
Sepsis
induced responses consistent with NTIS, resulted in mitochondrial damage and functional impairment, and modulated the expression of key antioxidant enzymes in the diaphragm. Thus, impaired diaphragm function during
sepsis
seems to involve altered local TH signaling, mitochondrial dysfunction, and oxidative stress defense.
...
PMID:Sepsis Impairs Thyroid Hormone Signaling and Mitochondrial Function in the Mouse Diaphragm. 3220 Jul 9
