Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Classic therapeutics for ischemic heart disease are less effective in individuals with the metabolic syndrome. As the prevalence of the metabolic syndrome is increasing, better understanding of cardiac metabolism is needed to identify potential new targets for therapeutic intervention. Thioredoxin-interacting protein (Txnip) is a regulator of metabolism and an inhibitor of the antioxidant thioredoxins, but little is known about its roles in the myocardium. We examined hearts from Txnip-KO mice by polony multiplex analysis of gene expression and an independent proteomic approach; both methods indicated suppression of genes and proteins participating in mitochondrial metabolism. Consistently, Txnip-KO mitochondria were functionally and structurally altered, showing reduced oxygen consumption and ultrastructural derangements. Given the central role that mitochondria play during hypoxia, we hypothesized that Txnip deletion would enhance ischemia-reperfusion damage. Surprisingly, Txnip-KO hearts had greater recovery of cardiac function after an ischemia-reperfusion insult. Similarly, cardiomyocyte-specific Txnip deletion reduced infarct size after reversible coronary ligation. Coordinated with reduced mitochondrial function, deletion of Txnip enhanced anaerobic glycolysis. Whereas mitochondrial ATP synthesis was minimally decreased by Txnip deletion, cellular ATP content and lactate formation were higher in Txnip-KO hearts after ischemia-reperfusion injury. Pharmacologic inhibition of glycolytic metabolism completely abolished the protection afforded the heart by Txnip deficiency under hypoxic conditions. Thus, although Txnip deletion suppresses mitochondrial function, protection from myocardial ischemia is enhanced as a result of a coordinated shift to enhanced anaerobic metabolism, which provides an energy source outside of mitochondria.
 ...
PMID:Deletion of thioredoxin-interacting protein in mice impairs mitochondrial function but protects the myocardium from ischemia-reperfusion injury. 2220 73

Empirical evidence indicates a strong association between insulin resistance and pathological alterations related to Alzheimer's disease (AD) in different cerebral regions. While cerebral insulin resistance is not essentially parallel with systemic metabolic derangements, type 2 diabetes mellitus (T2DM) has been established as a risk factor for AD. The circulating "toxic metabolites" emerging in metabolic syndrome may engage several biochemical pathways to promote oxidative stress and neuroinflammation leading to impair insulin function in the brain or "type 3 diabetes". Thioredoxin-interacting protein (TXNIP) as an intracellular amplifier of oxidative stress and inflammasome activation may presumably mediate central insulin resistance. Emerging data including those from our recent studies has demonstrated a sharp TXNIP upregulation in stroke, aging and AD and well underlining the significance of this hypothesis. With the main interest to illustrate TXNIP place in type 3 diabetes, the present review primarily briefs the potential mechanisms contributing to cerebral insulin resistance in a metabolically deranged environment. Then with a particular focus on plausible TXNIP functions to drive and associate with AD pathology, we present the most recent evidence supporting TXNIP as a promising therapeutic target in AD as an age-associated dementia.
 ...
PMID:Metabolic Syndrome, Brain Insulin Resistance, and Alzheimer's Disease: Thioredoxin Interacting Protein (TXNIP) and Inflammasome as Core Amplifiers. 3037 83

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors for all-cause mortality, cardiovascular disease, and cancer. Identifying epigenetic alterations associated with MetS in African Americans (AAs) and Whites may provide insight into genes that influence its differential health outcomes. We examined DNA methylation (DNAm) and performed an epigenome-wide association study (EWAS) of MetS among AAs and Whites with and without MetS. We assessed age, race and poverty status associated DNAm among AAs (n = 225) and White (n = 233) adults using NCEP-ATP III guidelines. Genome-wide DNAm measurement was assessed using Illumina Infinium Methylation EPIC BeadChip. Differentially methylated positions (DMPs) and differentially methylated regions (DMRs) were identified using dmpFinder and bumphunter. EWAS was performed using CpGassoc. We found significant DMPs associated with age, poverty status and MetS in each race. GSTT1(Glutathione S-Transferase Theta 1) was one of the top-hypermethylated genes and MIPEP (Mitochondrial Intermediate Peptidase) was one of the most hypomethylated genes when comparing AAs with and without MetS. PPP1R13L (Protein Phosphatase 1 Regulatory Subunit 13 Like) was the top hypermethylated and SCD (stearoyl-CoA desaturase-1) was one of the most hypomethylated genes for Whites with and without MetS. EWAS results showed that DNAm differences might contribute to MetS risk among Whites and AAs since different genes were identified in AAs and Whites. We replicated previously identified MetS associated genes and found that Thioredoxin-interacting protein (TXN1P) was statistically significantly differentially expressed only in Whites. Our results may be useful in further studies of genes underlying differences in MetS among AAs and Whites.
 ...
PMID:Race-specific alterations in DNA methylation among middle-aged African Americans and Whites with metabolic syndrome. 3173 26