RNA-seq reveal role of bovine TORC2 in the regulation of adipogenesis.
RNA-seq 揭示了牛 TORC2 在脂肪形成调控中的作用。
- 作者列表："Khan R","Raza SHA","Junjvlieke Z","Wang H","Cheng G","Smith SB","Jiang Z","Li A","Zan L
:Low intramuscular adipose tissue (marbling) continues to be challenge for improving beef quality in Chinese cattle. Highly marbled meat is very desirable; hence, methods to increase IMF content have become a key aspect of improving meat quality. Therefore, research on the mechanism of adipogenesis provides invaluable information for the improvement of meat quality. This study investigated the effect of TORC2 and its underlying mechanism on lipid metabolism in bovine adipocytes. The TORC2 gene was downregulated in bovine adipocytes by siRNA, and RNA sequencing was performed. Downregulation of TORC2 negatively affected bovine adipocyte differentiation. In addition, a total of 577 DEGs were found, containing 146 up-regulated and 376 down-regulated genes. KEGG pathway analysis revealed that the DEGs were linked with neuroactive ligand-receptor interaction pathway, calcium signaling pathway, cAMP pathway, chemokine signaling pathway and Wnt signaling pathway. Gene Ontology (GO) term analysis of the DEGs showed that down-regulation of TORC2 gene significantly suppressed the genes regulating important GO terms of adipogenesis-related processes in bovine adipocytes, especially regulation of biological activity, regulation of primary metabolic process, regulation of multicellular organismal process, cell adhesion, lipid metabolic process, secretion, chemical homeostasis, regulation of transport, cell-cell signaling, cAMP metabolic process, cellular calcium ion homeostasis, fat cell differentiation, and cell maturation. In conclusion, our results suggest that TORC2 at least in part regulates lipid metabolism in bovine adipocytes. The results of this study provide a basis for studying the function and molecular mechanism of the TORC2 gene in regulating adipogenesis.
: 低肌内脂肪组织 (大理石花纹) 仍然是提高中国牛牛肉质量的挑战。高度大理石状的肉是非常可取的; 因此，提高 IMF 含量的方法已经成为改善肉类质量的一个关键方面。因此，对脂肪形成机制的研究为改善肉品质提供了宝贵的信息。本研究探讨 TORC2 对牛脂肪细胞脂质代谢的影响及其机制。通过 siRNA 在牛脂肪细胞中下调 TORC2 基因，并进行 RNA 测序。TORC2 的下调对牛脂肪细胞分化产生负面影响。此外，共发现 577 个 DEGs，包含 146 个上调和 376 个下调基因。KEGG 通路分析发现 DEGs 与神经活性配体-受体相互作用通路、钙信号通路、 cAMP 通路、趋化因子信号通路和 Wnt 信号通路相关联。DEGs 的 Gene Ontology (GO) 术语分析表明，TORC2 基因的下调显著抑制了调控牛脂肪细胞脂肪形成相关过程中重要 GO 术语的基因, 尤其是生物活性的调节、初级代谢过程的调节、多细胞生物过程的调节、细胞粘附、脂质代谢过程、分泌、化学稳态、转运调节、细胞-细胞信号传导、 cAMP 代谢过程、细胞钙离子稳态、脂肪细胞分化和细胞成熟。总之，我们的结果表明 TORC2 至少部分调节牛脂肪细胞的脂质代谢。本研究结果为研究 TORC2 基因调控脂肪形成的功能和分子机制提供了依据。
METHODS:BACKGROUND:Given the importance of habitual dietary protein intake, distribution patterns and dietary sources in the aetiology of age-related declines of muscle mass and function, the present study examined these factors as a function of sex and age in Irish adults aged 18-90 years comprising The National Adult Nutrition Survey (NANS). METHODS:In total, 1051 (males, n = 523; females, n = 528) undertook a 4-day semi-weighed food diary. Total, body mass relative intake and percentage contribution to total energy intake of dietary protein were determined in addition to protein distribution scores (PDS), as well as the contribution of food groups, animal- and plant-based foods to total protein intake. RESULTS:Total and relative protein intake [mean (SD)] were highest in those aged 18-35 years [96 (3) g day , 1.32 (0.40) g kg day ], with lower protein intakes with increasing age (i.e. in adults aged ≥65 years [82 (22) g, 1.15 (0.34) g kg day , P < 0.001 for both]. Differences in protein intake between age groups were more pronounced in males compared to females. Protein distribution followed a skewed pattern for all age groups [breakfast, 15 (10) g; lunch, 30 (15) g; dinner, 44 (17) g]. Animal-based foods were the dominant protein source within the diet [63% (11%) versus 37% (11%) plant protein, P < 0.001]. CONCLUSIONS:Protein intake and the number of meals reaching the purported threshold for maximising post-prandial anabolism were highest in young adults, and lower with increasing age. For main meals, breakfast provided the lowest quantity of protein across all age categories and may represent an opportunity for improving protein distribution, whereas, in older adults, increasing the number of meals reaching the anabolic threshold regardless of distribution pattern may be more appropriate.
METHODS:BACKGROUND:Low cardiorespiratory fitness (CRF) increases risk of all-cause mortality and cardiovascular events. Periodic CRF assessment can have an important preventive function. OBJECTIVE:To develop a protocol-free method to estimate CRF in daily life based on heart rate (HR) and body acceleration measurements. METHODS:Acceleration and HR data were collected from 37 subjects (M=49%) while performing a standardized laboratory activity protocol (sitting, walking, running, cycling) and during a 5-days free-living monitoring period. CRF was determined by oxygen uptake (VO2max) during maximal exercise testing. A doubly-labeled water validated equation was used to predict total energy expenditure (TEE) from acceleration data. A fitness index was defined as the ratio between TEE and HR (TEE-pulse). Activity recognition techniques were used to process acceleration features and classify sedentary, ambulatory and other activity types. Regression equations based on TEE-pulse data from each activity type were developed to predict VO2max. RESULTS:TEE-pulse measured within each activity type of the laboratory protocol was highly correlated to VO2max (r from 0.74 to 0.91). Averaging the outcome of each activity-type specific equation based on TEE-pulse from the laboratory data led to accurate estimates of VO2max (RMSE: 300.0 mlO2/min or 10%). The difference between laboratory and free-living determined TEE-pulse was 3.7 ± 11% (r =0.85). The prediction method preserved the prediction accuracy when applied to free-living data (RMSE: 367 mlO2/min or 12%). CONCLUSIONS:Measurements of body acceleration and HR can be used to predict VO2max in daily life. Activity-specific prediction equations are needed to achieve highly accurate estimates of CRF.
METHODS:OBJECTIVE:Postprandial dyslipidemia is a common feature of insulin resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. While bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Approach and Results: Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and with deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA effects (but not DCA) were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the anti-diabetic hormone glucagon-like peptide-1 (GLP-1). While the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate limiting enzyme for bile acid synthesis. CONCLUSIONS:Bile acid signaling may be an important mechanism of controlling dietary lipid absorption and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.