scholarly journals Gold Nanoclusters Eliminate Obesity Induced by Antipsychotics

2022 ◽  
Author(s):  
Meng He ◽  
Jing Yao ◽  
Zijun Zhang ◽  
Ying Zhang ◽  
Rui Chen ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Rat Model ◽  
Potential Application ◽  
Uncoupling Protein ◽  
Gold Nanoclusters ◽  
General Obesity ◽  
Uncoupling Protein 1 ◽  
H1 Receptor ◽  
Histamine H1 Receptor ◽  
Good Biocompatibility

Abstract Obesity induced by antipsychotics have plagued more than 20 million people worldwide. However, no drug is available to eliminate the obesity induced by antipsychotics. Here we examined the effect and potential mechanisms of a gold nanoclusters (AuNCs) modified by N-isobutyryl-L-cysteine on the obesity induced by olanzapine, the most prescribed but obesogenic antipsychotics, in a rat model. Our results showed that AuNCs completely prevented and reversed the obesity induced by olanzapine and improved glucose metabolism profile in rats. Further mechanism investigations revealed that AuNCs exert its anti-obesity function through inhibition of olanzapine-induced dysfunction of histamine H1 receptor and proopiomelanocortin signaling therefore reducing hyperphagia, and reversing olanzapine-induced inhibition of uncoupling-protein-1 signaling which increases thermogenesis. Together with AuNCs’ good biocompatibility, these findings not only provide AuNCs as a promising nanodrug candidate for treating obesity induced by antipsychotics, but also open an avenue for the potential application of AuNCs-based nanodrugs in treating general obesity

scholarly journals Uncoupling protein 1 knockout aggravates isoproterenol-induced acute myocardial ischemia via AMPK/mTOR/PPARα pathways in rats

2021 ◽  
Author(s):  
Daorong Hou ◽  
Heling Fu ◽  
Yuan Zheng ◽  
Dan Lu ◽  
Yuanwu Ma ◽  
...  
Keyword(s):  
Myocardial Ischemia ◽  
Rat Model ◽  
Troponin I ◽  
Uncoupling Protein ◽  
Heart Tissue ◽  
Acute Myocardial Ischemia ◽  
Energy Regulation ◽  
Uncoupling Protein 1 ◽  
Mtor Inhibition ◽  
Brown Adipose

AbstractUncoupling protein 1 (UCP1) was found exclusively in the inner membranes of the mitochondria of brown adipose tissue (BAT). We found that UCP1 was also expressed in heart tissue and significantly upregulated in isoproterenol (ISO)-induced acute myocardial ischemia (AMI) rat model. The present study is to determine the underlying mechanism involved in the UCP1 upregulation in ISO-induced AMI rat model. The Ucp1−/− rats were generated by CRISPR-Cas9 system and presented decreased BAT volume. 2-months old Sprague Dawley (SD) wild-type (WT) and Ucp1−/− rats were treated with ISO intraperitoneally 30 mg/kg once a day for 3 consecutive days to establish AMI model. In saline group, the echocardiographic parameters, serum markers of myocardial injury cardiac troponin I (cTnI), creatine kinase isoenzyme MB (CK-MB), oxidant malondialdehyde (MDA), antioxidant superoxide dismutase (SOD) or fibrosis were comparable between WT and Ucp1−/− rats. ISO treatment induced worse left ventricle (LV) hypertrophy, myocardial fibrosis, increased higher cTnI, CK-MB and MDA and decreased lower SOD level in Ucp1−/− rats compared with that of WT rats. Ucp1−/− rats also presented lower myocardial phosphocreatine (PCr)/ATP-ratio, which demonstrated worse cardiac energy regulation defect. ISO treatment induced the phosphorylation of AMP-activated protein kinase (AMPK) activation, subsequently the phosphorylation of mammalian target of rapamycin (mTOR) inhibition and peroxisome proliferators-activated receptor α (PPARα) activation in WT rats, whereas activation of AMPK/mTOR/PPARα pathways significantly inhibited in Ucp1−/− rats. To sum up, UCP1 knockout aggravated ISO-induced AMI by inhibiting AMPK/mTOR/PPARα pathways in rats. Increasing UCP1 expression in heart tissue may be a cytoprotective therapeutic strategy for AMI.

Evidence of Browning of White Adipocytes in Poorly Survived Fat Grafts in Patients

2021 ◽  
Author(s):  
Tong Liu ◽  
Su Fu ◽  
Qian Wang ◽  
Hao Cheng ◽  
Dali Mu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Uncoupling Protein ◽  
Fold Increase ◽  
Fat Grafting ◽  
Electronic Microscopy ◽  
Uncoupling Protein 1 ◽  
Fat Transfer ◽  
Flap Transfer ◽  
Fat Grafts ◽  
White Adipocytes

Abstract Background Browning adipocytes induced by burn and cancer were assumed less viable and more prone to necrosis for their hypermetabolic properties. Recent studies have shown browning of white adipose after fat engraftment in mice. Objectives We tend to evaluate whether fat transfer could induce browning biogenesis in fat grafts in humans and if it is associated with graft necrosis. Methods Necrotic adipose grafts were excised from 11 patients diagnosed with fat necrosis after fat grafting or flap transfer. Non-necrotic fat grafts were from 5 patients undergoing revisionary surgeries after flap transfer. Histology and electronic microscopy, protein and gene expression of browning related marker analyses were performed. Results Fat grafts with necrosis demonstrated a higher gene expression level of uncoupling protein-1 (>5-fold increase, **p<0.01), a master beige adipocyte marker, than non-necrotic fat grafts. Electronic microscopy and histology showed that browning adipocytes were presented in necrotic adipose in patients. Conclusions Fat transfer induced browning adipocytes in patients and was evident in patients with post grafting necrosis.

scholarly journals Design of Phthalazinone Amide Histamine H1 Receptor Antagonists for Use in Rhinitis

2017 ◽  
Vol 8 (5) ◽  
pp. 577-581 ◽  
Author(s):  
Panayiotis A. Procopiou ◽  
Alison J. Ford ◽  
Paul M. Gore ◽  
Brian E. Looker ◽  
Simon T. Hodgson ◽  
...  
Keyword(s):  
H1 Receptor ◽  
Receptor Antagonists ◽  
Histamine H1 Receptor

Growth factor regulation of uncoupling protein-1 mRNA expression in brown adipocytes

2002 ◽  
Vol 282 (1) ◽  
pp. C105-C112 ◽  
Author(s):  
Bibian García ◽  
Maria-Jesús Obregón
Keyword(s):  
Growth Factor ◽  
Adipocyte Differentiation ◽  
Uncoupling Protein ◽  
Brown Adipocyte ◽  
Mrna Levels ◽  
Uncoupling Protein 1 ◽  
Brown Adipocytes ◽  
Proliferation And Differentiation ◽  
Epidermal Growth ◽  
Continuous Presence

To study the effect of the mitogens epidermal growth factor (EGF), acidic and basic fibroblast growth factors (aFGF and bFGF), and vasopressin on brown adipocyte differentiation, we analyzed the expression of uncoupling protein-1 (UCP-1) mRNA. Quiescent brown preadipocytes express high levels of UCP-1 mRNA in response to triiodothyronine (T3) and norepinephrine (NE). The addition of serum or the mitogenic condition aFGF + vasopressin + NE or EGF + vasopressin + NE decreases UCP-1 mRNA. A second addition of mitogens further decreases UCP-1 mRNA. Treatment with aFGF or bFGF alone increases UCP-1 mRNA, whereas the addition of EGF or vasopressin dramatically reduces UCP-1 mRNA levels. The continuous presence of T3 increases UCP-1 mRNA levels in cells treated with EGF, aFGF, or bFGF. The effect of T3 on the stimulation of DNA synthesis also was tested. T3 inhibits the mitogenic activity of aFGF and bFGF. In conclusion, mitogens like aFGF or bFGF allow brown adipocyte differentiation, whereas EGF and vasopressin inhibit the differentiation process. T3 behaves as an important hormone that regulates both brown adipocyte proliferation and differentiation.

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