Shi Li's research while affiliated with Duke University and other places

... PPARα is highly expressed in the liver, heart, brown adipose tissue, and kidney; it is also found in skeletal muscle. Among other roles, it has an important function in fatty acid catabolism [70][71][72][73][74][75]. PPARα regulates the peroxisomal and mitochondrial β-oxidation, and the microsomal ω-oxidation of fatty acids. ...

... The demonstration that peroxisome proliferator-activated receptor a (PPARa) expression was increased, which may favour a switch towards mitochondrial uncoupling and greater fatty acid oxidation with consequent glycogen sparing, is challenging to this interpretation [29]. It may be that PPARa has other important regulatory actions at HA such as regulating mitochondrial function [29,32]. Proteomic analysis on the same subjects provides further support for the downregulation of aerobic metabolism with a decrement of the TCA cycle enzymes regulating the fate of a-KG (IDH2,OGDH) and fatty acid metabolism (ACADVL, ACADS) in the early but, particularly, in the late phase of acclimatization [33]. ...

... In addition, ATF4 promotes PPP1R15A expression, which subsequently induces the expression of DNA damage-inducible 34 (GADD34), a regulatory subunit of protein phosphatase 1 (PP1); this results in dephosphorylation of eIF2a, leading to restoration of mRNA translation (26). When ER stress is intense or persistent, ATF4 additionally promotes pro-apoptotic factors, such as C/EBP homologous protein (CHOP), and enhances oxidative stress, leading to cell death (27). ...

... In mammals, three genes (PPP1CA, PPP1CB, and PPP1CC) encode four isoforms of the catalytic subunit of PP1: PP1α, PP1β, PP1γ1, and PP1γ2. These four isoforms are expressed in all tissues and compartments, although PP1γ2 is only expressed in testes [10,57,58,64,[67][68][69][70][71]. In addition, all isoforms are found in the nucleus, but PP1β and PP1γ present a special accumulation in the nucleolus [57]. ...

... Activation of S6K occurs with phosphorylation of the four C-terminal serine residues, thereby exposing the linker region which is subsequently accessible for mTORC1 phosphorylation. Ultimately, phosphorylation mediated by PDK1 is performed at the threonine residue of the kinase domain, activating S6K [223,224,228,229]. Both S6K isoforms are implicated in diverse biological processes such as cytoskeleton reorganization, protein synthesis, signal transduction, transcription, and splicing, which are all dysregulated in the FXS [223,230]. ...

... Since PGC-1α4 is a co-activator, it is required to interact with a nuclear receptor to drive the transcription of its target genes. Peroxisome proliferator-activated receptor β (PPARβ) is a dominant nuclear receptor in skeletal muscle 25,44,45 . We identified that acute RE rapidly increases PPARβ gene expression (Fig. 5A) and RET increases PPARβ protein abundance in skeletal muscle (Fig. 5B). ...

... The latter might be of particular interest as initial studies have revealed an important function of protein arginine methyltransferases for the development of heart failure [69] . Finally, there was an initial report about I-1 splicing, leading to at least three variants in brain and liver tissues with different c-termini that seems to have age-dependent expression patterns [70]. The functional impact of these different splice variants and their expression in cardiac tissue are unresolved so far. ...