| Title |
Elevated circulating stearic acid leads to a major lipotoxic effect on mouse pancreatic beta cells in hyperlipidaemia via a miR-34a-5p-mediated PERK/p53-dependent pathway
|
|---|---|
| Published in |
Diabetologia, March 2016
|
| DOI | 10.1007/s00125-016-3900-0 |
| Pubmed ID | |
| Authors |
Huimin Lu, Liuyi Hao, Songtao Li, Song Lin, Lin Lv, Yang Chen, Hongli Cui, Tianqi Zi, Xia Chu, Lixin Na, Changhao Sun |
| Abstract |
Serum stearic acid (C18:0) is elevated in individuals with hyperlipidaemia and type 2 diabetes. However, the lipotoxicity induced by increased stearic acid in beta cells has not been well described. This study aimed to examine the adverse effects of stearic acid on beta cells and the potential mechanisms through which these are mediated. Three groups of C57BL/6 mice were fed a normal diet or a high-stearic-acid/high-palmitic-acid diet for 24 weeks, respectively. The microRNA (miR) profiles of islets were determined by microarray screening. Islet injury was detected with co-staining using the TUNEL assay and insulin labelling. A lentiviral vector expressing anti-miRNA-34a-5p oligonucleotide (AMO-34a-5p) was injected into mice via an intraductal pancreatic route. In both mouse islets and cultured rat insulinoma INS-1 cells, stearic acid exhibited a stronger lipotoxic role than other fatty acids, owing to repression of B cell CLL/lymphoma 2 (BCL-2) and BCL-2-like 2 (BCL-W) by stearic acid stimulation of miR-34a-5p. The stearic-acid-induced lipotoxicity and reduction in insulin secretion were alleviated by AMO-34a-5p. Further investigations in INS-1 cells revealed that p53 was involved in stearic-acid-induced elevation of miR-34a-5p, owing in part to activation of protein kinase-like endoplasmic reticulum kinase (PERK). Conversely, silencing PERK alleviated stearic-acid-induced p53, miR-34a-5p and lipotoxicity. These findings provide new insight for understanding the molecular mechanisms underlying not only the deleterious impact of stearic-acid-induced lipotoxicity but also apoptosis in beta cells and progression to type 2 diabetes. |
X Demographics
The data shown below were collected from the profiles of 4 X users who shared this research output. Click here to find out more about how the information was compiled.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 4 | 100% |
Demographic breakdown
| Type | Count | As % |
|---|---|---|
| Members of the public | 3 | 75% |
| Science communicators (journalists, bloggers, editors) | 1 | 25% |
Mendeley readers
The data shown below were compiled from readership statistics for 56 Mendeley readers of this research output. Click here to see the associated Mendeley record.
Geographical breakdown
| Country | Count | As % |
|---|---|---|
| Unknown | 56 | 100% |
Demographic breakdown
| Readers by professional status | Count | As % |
|---|---|---|
| Student > Ph. D. Student | 9 | 16% |
| Researcher | 7 | 13% |
| Student > Bachelor | 6 | 11% |
| Student > Postgraduate | 3 | 5% |
| Other | 2 | 4% |
| Other | 6 | 11% |
| Unknown | 23 | 41% |
| Readers by discipline | Count | As % |
|---|---|---|
| Biochemistry, Genetics and Molecular Biology | 15 | 27% |
| Agricultural and Biological Sciences | 8 | 14% |
| Medicine and Dentistry | 5 | 9% |
| Pharmacology, Toxicology and Pharmaceutical Science | 1 | 2% |
| Nursing and Health Professions | 1 | 2% |
| Other | 3 | 5% |
| Unknown | 23 | 41% |
Attention Score in Context
This research output has an Altmetric Attention Score of 3. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 17 February 2022.
All research outputs
#13,410,854
of 23,146,350 outputs
Outputs from Diabetologia
#4,243
of 5,099 outputs
Outputs of similar age
#141,699
of 300,373 outputs
Outputs of similar age from Diabetologia
#58
of 83 outputs
Altmetric has tracked 23,146,350 research outputs across all sources so far. This one is in the 41st percentile – i.e., 41% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 83 others from the same source and published within six weeks on either side of this one. This one is in the 27th percentile – i.e., 27% of its contemporaries scored the same or lower than it.