scholarly journals Paired related homeobox 1 attenuates autophagy via acetyl‐CoA carboxylase 1‐regulated fatty acid metabolism in salivary adenoid cystic carcinoma

FEBS Open Bio ◽  
2022 ◽  
Author(s):  
Jie Gao ◽  
Kangjie Ma ◽  
Li Zhang ◽  
Tao Li ◽  
Baodong Zhao ◽  
...  
2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Hua Yang ◽  
Fei Wang ◽  
Xinya Guo ◽  
Feng Liu ◽  
Zhonghua Liu ◽  
...  

AbstractPathogenic mycobacteria induce the formation of hypoxic granulomas during latent tuberculosis (TB) infection, in which the immune system contains, but fails to eliminate the mycobacteria. Fatty acid metabolism-related genes are relatively overrepresented in the mycobacterial genome and mycobacteria favor host-derived fatty acids as nutrient sources. However, whether and how mycobacteria modulate host fatty acid metabolism to drive granuloma progression remains unknown. Here, we report that mycobacteria under hypoxia markedly secrete the protein Rv0859/MMAR_4677 (Fatty-acid degradation A, FadA), which is also enriched in tuberculous granulomas. FadA acts as an acetyltransferase that converts host acetyl-CoA to acetoacetyl-CoA. The reduced acetyl-CoA level suppresses H3K9Ac-mediated expression of the host proinflammatory cytokine Il6, thus promoting granuloma progression. Moreover, supplementation of acetate increases the level of acetyl-CoA and inhibits the formation of granulomas. Our findings suggest an unexpected mechanism of a hypoxia-induced mycobacterial protein suppressing host immunity via modulation of host fatty acid metabolism and raise the possibility of a novel therapeutic strategy for TB infection.


2021 ◽  
Author(s):  
G. Sushma ◽  
P. Jaya Laxmi ◽  
S.T. Viroji Rao ◽  
R.M.V. Prasad ◽  
M. Kanakachari ◽  
...  

Abstract The poultry industry provides cost-effective, healthy, and protein-enriched food for the growing population and achieving the nutritional security to the country. Excessive abdominal and subcutaneous fat deposition is one of the major setbacks to the poultry industry that reduces carcass yield and feed efficiency. In chicken abdominal fat constitutes 20% of total body fat which make up 2–3% of live weight of the bird. In fatty acid metabolism, acetyl-CoA Carboxylase (ACC) is one of the key enzymes with two isoforms i.e. ACACA and ACACB each of which plays a different role. In chicken, ACACB is involved in the β-oxidation of fatty acids and thereby potentially regulating the quality of meat and egg. The RNAi strategy is widely used for silencing the target gene expression. In this study, we designed five shRNA constructs and identified the most efficient shRNA molecule for silencing the ACACB gene under in vitro chicken embryo myoblast (CEM) primary cell culture system. After knocking down the ACACB gene, for understanding how fatty acid metabolism is regulated, we tracked the expression of key fatty acid metabolism genes like ACACA, FASN, SCD, ELOVL2, and CPT1. Also, checked the expression of immune response genes like IFNA, IFNB, and BLB1 in control as well as ACACB knockdown myoblast cells and observed no significant difference. We observed the down-regulation of key fatty acid metabolism genes along with ACACB, which may leads to the less fat accumulation in CEM cells. We also estimated the cholesterol and triglycerides in control and ACACB knockdown myoblast cells and found a significant difference between control and the knockdown cells. In vitro knockdown of the ACACB gene in a cell culture system by a short hairpin RNA (shRNA) expressing construct would help to produce a knockdown chicken with reduced fat deposition.


2014 ◽  
Vol 289 (36) ◽  
pp. 25382-25392 ◽  
Author(s):  
Lia R. Edmunds ◽  
Lokendra Sharma ◽  
Audry Kang ◽  
Jie Lu ◽  
Jerry Vockley ◽  
...  

2015 ◽  
Vol 290 (33) ◽  
pp. 20100-20100 ◽  
Author(s):  
Lia R. Edmunds ◽  
Lokendra Sharma ◽  
Audry Kang ◽  
Jie Lu ◽  
Jerry Vockley ◽  
...  

1990 ◽  
Vol 29 (01) ◽  
pp. 28-34 ◽  
Author(s):  
F. C. Visser ◽  
M. J. van Eenige ◽  
G. Westera ◽  
J. P. Roos ◽  
C. M. B. Duwel

Changes in myocardial metabolism can be detected externally by registration of time-activity curves after administration of radioiodinated fatty acids. In this scintigraphic study the influence of lactate on fatty acid metabolism was investigated in the normal human myocardium, traced with 123l-17-iodoheptadecanoic acid (123l-17-HDA). In patients (paired, n = 7) lactate loading decreased the uptake of 123l-17-HDA significantly from 27 (control: 22-36) to 20 counts/min/pixel (16-31; p <0.05 Wilcoxon). The half-time value increased to more than 60 rriin (n = 5), oxidation decreased from 61 to 42%. Coronary vasodilatation, a well-known side effect of lactate loading, was studied separately in a dipyridamole study (paired, n = 6). Coronary vasodilatation did not influence the parameters of the time-activity curve. These results suggest that changes in plasma lactate level as occurring, among other effects, during exercise will influence the parameters of dynamic 123l-17-HDA scintigraphy of the heart.


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