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

Aerobic conditioned muscle shows increased oxidative metabolism or glucose relative to untrained muscle at a given absolute exercise intensity. The studies of a targeted risk reduction intervention through defined exercise (STRRIDE) study is an aerobic exercise intervention in men and women with features of metabolic syndrome (Kraus WE, Torgan CE, Duscha BD, Norris J, Brown SA, Cobb FR, Bales CW, Annex BH, Samsa GP, Houmard JA, and Slentz CA, Med Sci Sports Exerc 33: 1774-1784, 2001), with four muscle biopsies taken during training and detraining time points. Here, we expanded a previous study (Hittel DS, Kraus WE, and Hoffman EP, J Physiol 548: 401-410, 2003) and used mRNA profiling to investigate gene transcripts associated with energy and substrate metabolism in STRRIDE participants. We found coordinate regulation of key metabolic enzymes with aerobic training in metabolic syndrome (aspartate aminotransferase 1, lactate dehydrogenase B, and pyruvate dehydrogenase-alpha(1)). All were also quickly downregulated by detraining, although the induction was not an acute response to activity. Protein and enzymatic assays were used to validate mRNA induction with aerobic training and loss with detraining (96 h to 2 wk) in 10 male and 10 female STRRIDE subjects. We propose that training coordinately increases the levels of aspartate aminotransferase 1, lactate dehydrogenase B, and pyruvate dehydrogenase-alpha(1) subunit, increasing glucose metabolism in muscle by liberating pyruvate for oxidative metabolism and, therefore, limiting lactate efflux. Serial measurement of fasting plasma lactate from 62 subjects from the same exercise group demonstrated a significant decrease of circulating lactate with training. We also found evidence for sex-specific molecular remodeling of muscle with ubiquinol-cytochrome c reductase core protein II, a component of mitochondrial respiratory complex III, which showed an increase after training that was specific to women. These biochemical adaptations complement existing molecular models for improved glucose tolerance with exercise intervention in prediabetic individuals.
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PMID:Exercise training increases electron and substrate shuttling proteins in muscle of overweight men and women with the metabolic syndrome. 1534 26

There is overwhelming evidence for an association between impaired mitochondrial function and metabolic syndrome. Mitophagy, a process that selectively removes damaged mitochondria via a specialized form of autophagy, is essential for mitochondrial quality control (mitochondrial QC) and metabolic homeostasis. We thus addressed the potential role of defective mitophagy in the pathogenesis of metabolic disorders. Mice lacking Fundc1, a newly characterized mitophagy receptor, develop more severe obesity and insulin resistance when fed a high-fat diet (HFD). Ablation of Fundc1 results in defective mitophagy and impaired mitochondrial QC in vitro and in white adipose tissue (WAT). In addition, there is more pronounced WAT remodeling with more adipose tissue-associated macrophages infiltration, more M1 macrophage polarization and thus an elevated inflammatory response. Mechanistically, hyperactivation of MAPK/JNK leads to insulin insensitivity, which can be inhibited by knocking out Mapk8/Jnk1 in fundc1 KO mice. Our results demonstrate that dysregulated mitochondrial QC due to defective mitophagy receptor FUNDC1 links with metabolic disorders via MAPK signaling and inflammatory responses. Abbreviations: ATMs: adipose tissue macrophages; BAT: brown adipose tissue; BMDMs: bone marrow-derived macrophages; GOT1/AST: glutamic-oxaloacetic transaminase 1, soluble; GPT/ALT: glutamic pyruvic transaminase, soluble; H&E staining: hematoxylin and eosin staining; HFD: high-fat diet; LIR: LC3-interacting region; mitochondrial QC: mitochondrial quality control; mito-ROS: mitochondrial ROS; mtDNA: mitochondrial DNA; RT-PCR: real-time-PCR; T2D: type 2 diabetes; WAT: white adipose tissue.
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PMID:Deficiency of mitophagy receptor FUNDC1 impairs mitochondrial quality and aggravates dietary-induced obesity and metabolic syndrome. 3089 10