bNonalcoholic fatty liver disease (NAFLD) has become the most common liver disease, and decreased fatty acid oxidation is one of the important contributors to NAFLD. Mitochondrial trifunctional protein ␣-subunit (MTP␣) functions as a critical enzyme for fatty acid ␤-oxidation, but whether dysregulation of MTP␣ is pathogenically connected to NAFLD is poorly understood. We show that MTP␣ is acetylated at lysine residues 350, 383, and 406 (MTP␣-3K), which promotes its protein stability by antagonizing its ubiquitylation on the same three lysines (MTP␣-3K) and blocking its subsequent degradation. Sirtuin 4 (SIRT4) has been identified as the deacetylase, deacetylating and destabilizing MTP␣. Replacement of MTP␣-3K with either MTP␣-3KR or MTP␣-3KQ inhibits cellular lipid accumulation both in free fatty acid (FFA)-treated alpha mouse liver 12 (AML12) cells and primary hepatocytes and in the livers of high-fat/high-sucrose (HF/HS) diet-fed mice. Moreover, knockdown of SIRT4 could phenocopy the effects of MTP␣-3K mutant expression in mouse livers, and MTP␣-3K mutants more efficiently attenuate SIRT4-mediated hepatic steatosis in HF/HS diet-fed mice. Importantly, acetylation of both MTP␣ and MTP␣-3K is decreased while SIRT4 is increased in the livers of mice and humans with NAFLD. Our study reveals a novel mechanism of MTP␣ regulation by acetylation and ubiquitylation and a direct functional link of this regulation to NAFLD.

Obesity is associated with chronic low-level inflammation, especially in fat tissues, which contributes to insulin resistance and type 2 diabetes mellitus (T2DM). Protein inhibitor of activated STAT 1 (PIAS1) modulates a variety of cellular processes such as cell proliferation and DNA damage responses. Particularly, PIAS1 functions in the innate immune system and is a key regulator of the inflammation cascade. However, whether PIAS1 is involved in the regulation of insulin sensitivity remains unknown. Here, we demonstrated that PIAS1 expression in white adipose tissue (WAT) was downregulated by c-Jun N-terminal kinase in prediabetic mice models. Overexpression of PIAS1 in inguinal WAT of prediabetic mice significantly improved systemic insulin sensitivity, whereas knockdown of PIAS1 in wild-type mice led to insulin resistance. Mechanistically, PIAS1 inhibited the activation of stress-induced kinases and the expression of nuclear factor-κB target genes in adipocytes, mainly including proinflammatory and chemotactic factors. In doing so, PIAS1 inhibited macrophage infiltration in adipose tissue, thus suppressing amplification of the inflammation cascade, which in turn improved insulin sensitivity. These results were further verified in a fat transplantation model. Our findings shed light on the critical role of PIAS1 in controlling insulin sensitivity and suggest a therapeutic potential of PIAS1 in T2DM.

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Background: Astrocytes are highly glycolytic cells that play a crucial role in chronic pain. Recently it has been found that inflammation and metabolism are related to the inflammatory stimuli closely that cause cellular metabolic changes. Pyruvate kinase M2 (PKM2) is a critical metabolic kinase in aerobic glycolysis or the Warburg effect. Besides, it also plays a crucial role in cell proliferation and signal transduction, but its role in astrocytes is still unclear. Methods:The chronic inflammatory pain model was set up by intraplantar injection of complete Freund's adjuvant (CFA) in Sprague Dawley (SD) rats as well as the cell model was constructed by lipopolysaccharidetreated primary astrocytes. Von Frey filament stimulation was used to continuously observe the changes of pain behavior in rats after modeling. Then, immunofluorescence staining and Western blot tests were used to observe the expression levels of glial fibrillary acidic protein (GFAP), pyruvate kinase (PKM2), signal transducers and activators of transcription 3 (STAT3) and high mobility group box-1 protein (HMGB1).After that, specific kits measured lactate contents. Finally, we observed the platelet-rich plasma's (PRP) effect on mechanical hyperalgesia in rats with inflammatory pain induced by CFA and its effect on related signal molecules.Results: We found that in the CFA-induced inflammatory pain model, astrocytes were significantly activated, GFAP was increased, PKM2 was significantly up-regulated, and the glycolytic product lactate was increased. Also, intrathecal injection of PRP increased the pain threshold, inhibited the activation of astrocytes, and decreased the expression of PKM2 and aerobic glycolysis; in LPS-activated primary astrocytes as an in vitro model, we found PKM2 translocation activationSTAT3 signaling resulted in sustained activation of astrocyte marker GFAP, and the expression level and localization of p-STAT3 were correlated with PKM2. PRP could inhibit the activation of astrocytes, reduce the expression of PKM2 and the expression levels of glycolysis and GFAP, GLUT1, and p-STAT3 in astrocytes.Conclusions: Our findings suggest PKM2 not only plays a glycolytic role in astrocytes, but also plays a crucial role in astrocyte-activated signaling pathways, and PRP attenuates CFA induced inflammatory pain by inhibiting aerobic glycolysis in astrocytes, providing a new therapeutic target for the treatment of inflammatory pain.

Liquid crystals (LC) have been found to have many unique characteristics during the last few decades. The liquid crystal phase is ubiquitous in the biological world, as well as in cellulose and its derivatives. Cellulose nanocrystals (CNC), which can obtain the chiral LC phase in aqueous suspension, have been attracting much attention. The unique size and properties of CNC, such as their light weight, special optical properties, non-toxicity, and biocompatibility, etc., have made them widely applicable in diverse fields. This brief literature review introduces the relationship between the LC phase and CNC. Advantages of CNC as a liquid crystal forming material and the preparation of CNC are discussed. The left-handed cholesteric phase structure and the corresponding unique optical properties of CNC-based LC are described in detail. The CNC-based LC aqueous suspension and three stages of forming LC phase are also described. Then, the main reasons accounting for the brittleness and non-uniformity of pristine CNC-based LC are summarized, as well as ways to overcome these problems. Finally, some optical applications of CNC-based LC films in anti-counterfeiting, colorimetric sensors, and composite devices are considered.