High-fat diet-induced obesity affects alpha 7 nicotine acetylcholine receptor expressions in mouse lung myeloid cells

Qi, Yong; Si, Dan; Zhu, Li; Qi, Yanan; Wu, Zhuhua; Chen, Dan; Yang, Yunlei

doi:10.1038/s41598-020-75414-w

Cited by 7 publications

(3 citation statements)

References 58 publications

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“…Six-week-old male C57BL/6 J mice were purchased from Beijing Vital River Laboratory Animal Technology Co. Ltd. Mice were kept in a temperature-controlled room (23–24 °C) under standard 12-hour light/dark conditions. According to previous literature [ 22 ], mice were randomly divided into DIO (diet-induced obesity) group with high-fat diet (D12492, Research Diets Inc., 60% kcal fat) or lean group with regular chow diet (Beijing Keao Xieli Feed Co., Ltd, 12% kcal fat) for a total of 12 weeks. For C-176 treatment, after 8 weeks feeding with high-fat diet or regular chow diet, the mice were randomly divided into three groups including DIO/C-176, DIO/vehicle, and lean/vehicle.…”

Section: Methodsmentioning

confidence: 99%

A role of STING signaling in obesity-induced lung inflammation

Chen

et al. 2023

Int J Obes

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Background It is established that pulmonary disorders are comorbid with metabolic disorders such as obesity. Previous studies show that the stimulator of interferon genes (STING) signaling plays crucial roles in obesity-induced chronic inflammation via TANK-binding kinase 1 (TBK1) pathways. However, it remains unknown whether and how the STING signaling is implicated in the inflammatory processes in the lung in obesity. Methods Human lung tissues were obtained from obese patients (n = 3) and controls (n = 3). Mice were fed with the high-fat diet or regular control diet to establish the diet-induced obese (DIO) and lean mice, and were treated with C-176 (a specific STING inhibitor) or vehicle respectively. The lung macrophages were exposed to palmitic acid (PA) in vitro. The levels of STING singaling and metabolic inflammation factors were detected and anlyzed. Results We find that STING+/CD68+ macrophages are increased in lung tissues in patients with obesity. Our data also show that the expressions of STING and the levels of proinflammatory cytokines are increased both in lung tissues and bronchoalveolar lavage fluid (BALF) in obesity compared to controls, and inhibition of the STING blunted the obesity-induced lung inflammation. Mechanistically, our data demonstrate that the STING signaling pathway is involved in the PA-induced inflammation through the STING-TBK1-IRF3 (interferon regulatory factor 3)/NF-κB (nuclear factor kappa B) pathways in the lung macrophages. Conclusions Our results collectively suggest that the STING signaling contributes to obesity-associated inflammation by stimulating proinflammatory processes in lung macrophages, one that may serve as a therapeutic target in ameliorating obesity-related lung dysfunctions.

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Section: Methodsmentioning

confidence: 99%

A role of STING signaling in obesity-induced lung inflammation

Chen

et al. 2023

Int J Obes

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“…Six-week-old mice were randomly divided into a regular chow diet (Beijing Keao Xieli Feed Co., Ltd, 12% kcal fat) group (lean) or a high-fat diet (Research Diets, D12492, 60% kcal fat) group [diet-induced obese (DIO)]. After feeding for 24 weeks, the mouse model of ALI was established according to the previous literature [21]. Briefly, mice were anesthetized with pentobarbital and LPS (O55:B5, L2880, Sigma, 100 μg dissolved in 50 μL of saline) or vehicle (50 μL of saline) was instilled intratracheally into both lean and DIO mice.…”

Section: Lps-induced Ali Murine Model and C75 Treatmentmentioning

confidence: 99%

Inhibition of fatty acid synthase protects obese mice from acute lung injury via ameliorating lung endothelial dysfunction

Zhu

Nie

et al. 2023

Respir Res

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Background Obesity has been identified as a risk factor for acute lung injury/acute respiratory distress syndrome (ALI/ARDS). However, the underlying mechanisms remain elusive. This study aimed to investigate the role of fatty acid synthase (FASN) in lipopolysaccharide (LPS)-induced ALI under obesity. Methods A high-fat diet-induced obese (DIO) mouse model was established and lean mice fed with regular chow diet were served as controls. LPS was intratracheally instilled to reproduce ALI in mice. In vitro, primary mouse lung endothelial cells (MLECs), treated by palmitic acid (PA) or co-cultured with 3T3-L1 adipocytes, were exposed to LPS. Chemical inhibitor C75 or shRNA targeting FASN was used for in vivo and in vitro loss-of-function studies for FASN. Results After LPS instillation, the protein levels of FASN in freshly isolated lung endothelial cells from DIO mice were significantly higher than those from lean mice. MLECs undergoing metabolic stress exhibited increased levels of FASN, decreased levels of VE-cadherin with increased p38 MAPK phosphorylation and NLRP3 expression, mitochondrial dysfunction, and impaired endothelial barrier compared with the control MLECs when exposed to LPS. However, these effects were attenuated by FASN inhibition with C75 or corresponding shRNA. In vivo, LPS-induced ALI, C75 pretreatment remarkably alleviated LPS-induced overproduction of lung inflammatory cytokines TNF-α, IL-6, and IL-1β, and lung vascular hyperpermeability in DIO mice as evidenced by increased VE-cadherin expression in lung endothelial cells and decreased lung vascular leakage. Conclusions Taken together, FASN inhibition alleviated the exacerbation of LPS-induced lung injury under obesity via rescuing lung endothelial dysfunction. Therefore, targeting FASN may be a potential therapeutic target for ameliorating LPS-induced ALI in obese individuals.

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“…The  receptor plays a crucial role in inflammation control in numerous pathophysiological conditions, including acute and chronic diseases such as obesity (Qi et al, 2020;Scabia et al, 2020) and atherosclerosis (Ulleryd et al, 2019). However, growing interest in  as a therapeutic target for treating inflammation came from studies showing that  expression in non-neuronal cells, i.e.…”

Section: Introductionmentioning

confidence: 99%