All-trans retinoic acid changes muscle fiber type via increasing GADD34 dependent on MAPK signal.

All-trans retinoic acid (ATRA) increases the sensitivity to unfolded protein response in differentiating leukemic blasts. The downstream transcriptional factor of PERK, a major arm of unfolded protein response, regulates muscle differentiation. However, the role of growth arrest and DNA damage-inducible protein 34 (GADD34), one of the downstream factors of PERK, and the effects of ATRA on GADD34 expression in muscle remain unclear. In this study, we identified ATRA increased the GADD34 expression independent of the PERK signal in the gastrocnemius muscle of mice. ATRA up-regulated GADD34 expression through the transcriptional activation of GADD34 gene via inhibiting the interaction of homeobox Six1 and transcription co-repressor TLE3 with the MEF3-binding site on the GADD34 gene promoter in skeletal muscle. ATRA also inhibited the interaction of TTP, which induces mRNA degradation, with AU-rich element on GADD34 mRNA via p-38 MAPK, resulting in the instability of GADD34 mRNA. Overexpressed GADD34 in C2C12 cells changes the type of myosin heavy chain in myotubes. These results suggest ATRA increases GADD34 expression via transcriptional and post-transcriptional regulation, which changes muscle fiber type.

Reduction of stearoyl-CoA desaturase (SCD) contributes muscle atrophy through the excess endoplasmic reticulum stress in chronic kidney disease.

Skeletal muscle atrophy is associated with mortality and poor prognosis in patients with chronic kidney disease (CKD). However, underlying mechanism by which CKD causes muscle atrophy has not been completely understood. The quality of lipids (lipoquality), which is defined as the functional features of diverse lipid species, has recently been recognized as the pathology of various diseases. In this study, we investigated the roles of the stearoyl-CoA desaturase (SCD), which catalyzes the conversion of saturated fatty acids into monounsaturated fatty acids, in skeletal muscle on muscle atrophy in CKD model animals. In comparison to control rats, CKD rats decreased the SCD activity and its gene expression in atrophic gastrocnemius muscle. Next, oleic acid blocked the reduction of the thickness of C2C12 myotubes and the increase of the endoplasmic reticulum stress induced by SCD inhibitor. Furthermore, endoplasmic reticulum stress inhibitor ameliorated CKD-induced muscle atrophy (the weakness of grip strength and the decrease of muscle fiber size of gastrocnemius muscle) in mice and the reduction of the thickness of C2C12 myotubes by SCD inhibitor. These results suggest that the repression of SCD activity causes muscle atrophy through excessive endoplasmic reticulum stress in CKD.

High-fat diets provoke phosphorus absorption from the small intestine in rats.

OBJECTIVE: The ratio of dietary carbohydrate to fat may affect phosphorus metabolism because both calcium and phosphorus are regulated by similar metabolic mechanisms, and a high-fat diet (HFD) induces deleterious effects on the absorption of dietary calcium. We hypothesized that an HFD induces an increase in phosphorus absorption. The aim of this study was to evaluate the effects of differences in the quantity and quality of dietary fat on phosphorus metabolism over the short- and long-term. METHODS: Eighteen 8-wk-old Sprague-Dawley male rats were fed an isocaloric diet containing varied ratios of carbohydrates to fat energy and sources of fat (control diet, HFD, and high- saturated fat diet [HF-SFA]). At 3 d and 7 wk after the allocation and initiation of the test diets, feces and urine were collected and used for phosphorus and calcium measurement. RESULTS: The fecal phosphorous concentration (F-Pi) was lower in the HF-SFA group than in the other two groups; however, the urine phosphorus concentration (U-Pi) was significantly higher in the HF-SFA group than the other two groups when the rats were fed over the short- (P < 0.01) and long -term (P < 0.01 versus control, P < 0.05 versus HFD group). There were no significant differences in type-IIa sodium-phosphate cotransporter (NaPi-2 a) and type-IIc sodium-phosphate cotransporter (NaPi-2 c) mRNA expression, which are renal phosphate transport-related genes; however, the expression of type-IIb sodium-phosphate cotransporter (NaPi-2 b) and type-III sodium-phosphate cotransporter (Pit-1) mRNA in the duodenum was higher in the HFD and HF-SFA groups than in the control group (P < 0.05), although there were no significant differences in these in the jejunum. CONCLUSIONS: The present results indicated that an HFD, particularly HF-SFA, increases intestinal phosphate absorption compared with control.