No abstract

Visceral fat is considered the genuine and harmful white adipose tissue (WAT) that is associated to development of metabolic disorders, cardiovascular disease, and cancer. Here, we present a new concept to turn the harmful visceral fat into a beneficial energy consumption depot, which is beneficial for improvement of metabolic dysfunctions in obese mice. We show that low temperature–dependent browning of visceral fat caused decreased adipose weight, total body weight, and body mass index, despite increased food intake. In high-fat diet–fed mice, low temperature exposure improved browning of visceral fat, global metabolism via nonshivering thermogenesis, insulin sensitivity, and hepatic steatosis. Genome-wide expression profiling showed upregulation of WAT browning–related genes including Cidea and Dio2. Conversely, Prdm16 was unchanged in healthy mice or was downregulated in obese mice. Surgical removal of visceral fat and genetic knockdown of UCP1 in epididymal fat largely ablated low temperature–increased global thermogenesis and resulted in the death of most mice. Thus, browning of visceral fat may be a compensatory heating mechanism that could provide a novel therapeutic strategy for treating visceral fat–associated obesity and diabetes.

Hypertension is the leading preventable cause of premature deaths worldwide. Although long non-coding RNA (lncRNA) metastasis associated lung adenocarcinoma transcript 1 (MALAT1) has been identified to play important roles in the development of cardiovascular diseases, the regulatory function of lncRNA MALAT1 in hypertension remains poorly understood. This study aimed to explore the role of lncRNA MALAT1 in spontaneously hypertensive rats (SHRs). LncRNA MALAT1 was determined to be elevated and MyoD to be reduced in myocardial tissues and thoracic aortic vascular tissues of SHRs. Over-expression of lncRNA MALAT1 caused severe myocardial fibrosis in SHRs. In addition, lncRNA MALAT1 over-expression in vitro enhanced arterial smooth muscle cells (ASMCs) activity and fibrosis of SHRs, which, was rescued by over-expressed MyoD. Furthermore, lncRNA MALAT1 transcripts were found to be highly enriched in the nucleus, and lncRNA MALAT1 suppressed the transactivation of MyoD. Moreover, lncRNA MALAT1 was found to recruit Suv39h1 to MyoD-binding loci, leading to H3K9me3 trimethylation and down-regulation of the target gene. Taken conjointly, this study revealed an important role of lncRNA MALAT1 in promoting cardiac remodeling in hypertensive rats by inhibiting the transcription of MyoD. These results highlight the value of lncRNA MALAT1 as a therapeutic target for the management of hypertension.

No abstract

Objectives: To determine whether steroidogenic enzyme expression is associated with the steroid secretory pattern of subclinical Cushing's syndrome (SCS) by investigating the mRNA and protein expression of CYP17 and CYP11B1 in SCS adenomas, normal adrenal cortices (NA), non-functional adrenal adenomas (NFA) and cortisol-producing adenomas (CPA). Methods: Total RNA and protein were extracted from 20 CPA, six SCS, 15 NFA, and eight NA. Real-time quantitative polymerase chain reaction (PCR) and western blotting analysis were performed to determine the mRNA and protein expression of CYP17 and CYP11B1 in different tissues. The expression of CYP17 and CYP11B1 in the adrenocortical tumors was compared expression in NA. Results: Expression of both CYP11B1 and CYP17 mRNA and protein was detected in all samples tested. The expression of CYP11B1 mRNA and protein was significantly higher in the CPA group than in the other groups and was slightly higher in SCS samples compared with NA and NFA samples (all P < 0.05). There was no significant difference in CYP11B1 mRNA and protein expression between NA and NFA samples (P > 0.05). The expression of CYP17 mRNA and protein in different tissues was similar to that of CYP11B1. Neither CYP11B1 nor CYP17 mRNA and protein expression was correlated with plasma cortisol or adrenocorticotrophin levels (all P > 0.05). Conclusions: In conclusion, CYP11B1 and CYP17 are overexpressed in subclinical CPA and their overexpression accounts for the increased production of cortisol that is characteristic of CPA.