Brown adipose tissue activation in a rat model of Parkinson’s disease

Wang, Wenjuan; Meng, Xia; Yang, Chun; Fang, Dongliang; Wang, Xuemeng; An, Jiaqiang; Zhang, Jingyi; Wang, Lulu; Lu, Tao; Ruan, Hai Bin; Gao, Yan

doi:10.1152/ajpendo.00049.2017

Cited by 14 publications

(9 citation statements)

References 26 publications

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“…Currently, an ablation of nerve bundles of bilateral BAT was used to abolish the function of BAT in vivo. In consistence with previous studies (48,49,61), the surgical denervation was confirmed by the significant elimination of TH in BAT in the current study. We found that whitening occurred in denervated of BAT as evidenced by the uniocular morphology and decreased levels of UCP1 protein.…”

Section: Discussionsupporting

confidence: 93%

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Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

Jia

Fang

et al. 2020

Preprint

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Beige adipocytes are emerging as an interesting issue in obesity and metabolism research. There is a neglected possibility that brown adipocytes are equally activated when external stimuli induce beige adipocytes. Thus, a question is whether beige adipocytes have the same functions as brown adipocytes when brown adipose tissue (BAT) is lacking. This question has not been well studied. Therefore we determine the beneficial effects of beige adipocytes upon cold challenge or CL316243 treatments in animal models of BAT ablation by surgical denervation. The data show that beige adipocytes partly contribute to impaired glucose metabolism resulting from denervated BAT. Whereas, we found that denervated BAT were activated by cold exposure and CL316243. Thus, we further used BAT-removal animal models to abolish BAT functions completely. We found that beige adipocytes upon cold challenge or CL316243 treatments independently improved impaired glucose metabolism in BAT-removal mice. The insulin signaling was activated in BAT-removal mice upon cold exposure. Whereas, both the activation of insulin signaling and up-regulation of glucose transporter expression were observed in BAT-removal mice with CL316243 treatments. The data show that beige adipocytes induced by cold exposure or CL316243 may have different mechanisms to improve impaired glucose metabolism. Beige adipocytes can also enhance energy expenditure and lipolytic activity of white adipose tissue when BAT is lacking. We provide direct evidences for the beneficial effect of beige adipocytes in glucose metabolism and energy expenditure in the absence of BAT in vivo.

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Section: Discussionsupporting

confidence: 93%

“…As previous descriptions (49)(50)(51)(52), mice received a surgical denervation or removal of BAT. Under a stereomicroscope, a midline incision in the skin was performed along the upper dorsal surface.…”

Section: Surgical Denervation and Removal Of Batmentioning

confidence: 99%

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

Jia

Fang

et al. 2020

Preprint

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“…Thermogenesis was identified as a deimination enriched KEGG pathway. Loss of body weight and fat mass is one of the non-motor symptoms of Parkinson's disease and has, amongst others, been related to brown fat tissue meditated thermogenesis [56]. Thermogenesis is related to mitochondrial function [57,58] and also linked to synaptic transmission and neurodegeneration [59].…”

Section: Discussionmentioning

confidence: 99%

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

Sancandi¹,

Uysal-Onganer

Kraev

et al. 2020

IJMS

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The identification of biomarkers for early diagnosis of Parkinson's disease (PD) is of pivotal importance for improving approaches for clinical intervention. The use of translatable animal models of pre-motor PD therefore offers optimal opportunities for novel biomarker discovery in vivo. Peptidylarginine deiminases (PADs) are a family of calcium-activated enzymes that contribute to protein misfolding through post-translational deimination of arginine to citrulline. Furthermore, PADs are an active regulator of extracellular vesicle (EV) release. Both protein deimination and extracellular vesicles (EVs) are gaining increased attention in relation to neurodegenerative diseases, including in PD, while roles in pre-motor PD have yet to be investigated. The current study aimed at identifying protein candidates of deimination in plasma and plasma-EVs in a rat model of pre-motor PD, to assess putative contributions of such post-translational changes in the early stages of disease. EV-cargo was further assessed for deiminated proteins as well as three key micro-RNAs known to contribute to inflammation and hypoxia (miR21, miR155, and miR210) and also associated with PD. Overall, there was a significant increase in circulating plasma EVs in the PD model compared with sham animals and inflammatory and hypoxia related microRNAs were significantly increased in plasma-EVs of the pre-motor PD model. A significantly higher number of protein candidates were deiminated in the pre-motor PD model plasma and plasma-EVs, compared with those in the sham animals. KEGG (Kyoto encyclopedia of genes and genomes) pathways identified for deiminated proteins in the pre-motor PD model were linked to "Alzheimer's disease", "PD", "Huntington's disease", "prion diseases", as well as for "oxidative phosphorylation", "thermogenesis", "metabolic pathways", "Staphylococcus aureus infection", gap junction, "platelet activation", "apelin signalling", "retrograde endocannabinoid signalling", "systemic lupus erythematosus", and "non-alcoholic fatty liver disease". Furthermore, PD brains showed significantly increased staining for total deiminated proteins in the brain vasculature in cortex and hippocampus, as well as increased immunodetection of deiminated histone H3 in dentate gyrus and cortex. Our findings identify EVs and post-translational protein deimination as novel biomarkers in early pre-motor stages of PD. Figure 2. EV characterisation from rat plasma. (A) Representative Nanosight graphs showing nanoparticle tracking analysis (NTA) analysis of plasma EV profiles from sham-treated rats (Sham; n = 3). (B) Representative Nanosight graphs showing NTA analysis of plasma EV profiles from the premotor PD rat models (PD; n = 3). (C) Western blotting (WB) confirms that rat plasma-EVs are positive for the EV-specific markers CD63 and flotillin-1 (Flot-1); the molecular weight standard is indicated in kilo Daltons (kDa). (D,E) Transmission electron microscopy (TEM) images showing EVs isolated from sham (D) and pre-motor PD model (PD; (E)) rat plasma, revea...

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“…RNA concentration was about 1500-3000 ng/μl determined with NanoDrop2000. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) analysis was performed as previously described [32]. The primer sets we used were as Table S.1.…”

Section: Coimmunoprecipitation and Gst Pull-down Assaysmentioning

confidence: 99%

The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis

Fang

et al. 2019

Metabolism

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The thermogenic brown adipose tissue (BAT) has been proposed as a potential target to prevent or treat obesity and related metabolic diseases. BAT secretes adipokines to regulate the thermogenic program in an autocrine or paracrine manner. Follistatin-like 1 (FSTL1), a glycoprotein involved in adipogenesis and obesity, however, the function of FSTL1 in BAT thermogenesis and in the regulation of systemic energy homeostasis are not fully understood. Methods: Whole-body ablation Fstl1 heterozygous mice (Fstl1 +/−) and its littermates control were injected with CL316,243 to assess energy balance. A series of FSTL1 overexpression and knockdown experiments were carried out to evaluate its function in regulating thermogenic gene expression in brown adipocytes. Results: FSTL1 expression was induced upon BAT activation during cold challenge or β3-adrenergic activation. FSTL1 haploinsufficiency in mice led to reduced thermogenic gene expression, impaired BAT recruitment, and decreased heat production. FSTL1 cell-autonomously promoted the β3-adrenergic signaling, which was required to upregulate PPARγ and UCP1 in brown adipocytes. Furthermore, only glycosylated FSTL1 could be secreted from brown adipocytes to induce the β3-adrenergic activation. Conclusions: Our results suggest FSTL1 as a novel stimulator of the β-adrenergic signaling and BAT thermogenesis.

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Brown adipose tissue activation in a rat model of Parkinson’s disease

Cited by 14 publications

References 26 publications

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

Beige adipocytes independently improve impaired glucose metabolism in the absence of brown adipose tissues in vivo

Protein Deimination Signatures in Plasma and Plasma-EVs and Protein Deimination in the Brain Vasculature in a Rat Model of Pre-Motor Parkinson’s Disease

The glycoprotein follistatin-like 1 promotes brown adipose thermogenesis

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