Obese Adipose Tissue Modulates Pro-inflammatory Responses of Mouse Airway Epithelial Cells

2021 ◽  
Author(s):  
Jennifer L Ather ◽  
Katherine E Van Der Vliet ◽  
Madeleine M Mank ◽  
Leah F Reed ◽  
Anne E Dixon ◽  
...  
Keyword(s):  
Weight Loss ◽  
Epithelial Cells ◽  
High Fat Diet ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Airway Epithelial ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet

Although recognized as an important endocrine organ, little is known about the mechanisms through which adipose tissue can regulate inflammatory responses in distant tissues, such as lung, that are affected by obesity. To explore potential mechanisms, male C57BL/6J mice were provided either high-fat diet, low-fat diet, or were provided a high-fat diet then switched to the low-fat diet to promote weight loss. Visceral adipocytes were then cultured in vitro to generate conditioned media (CM) that was used to treat both primary (MTEC) and immortalized (MTCC) airway epithelial cells. Adiponectin levels were greatly depressed in the CM from both obese and diet-switched adipocytes relative to mice continually fed the low-fat diet. MTEC from obese mice secreted higher baseline levels of inflammatory cytokines than MTEC from lean or diet-switched mice. MTEC treated with obese adipocyte CM increased their secretion of these cytokines compared to MTEC treated with lean CM. Diet-switched CM modestly decreased the production of cytokines compared to obese CM, and these effects were recapitulated when the CM was used to treat MTCC. Adipose stromal vascular cells from obese mice expressed genes consistent with an M1 macrophage phenotype and decreased eosinophil abundance compared to lean SVF, a profile that persisted in the lean diet-switched mice despite substantial weight loss. Soluble factors secreted from obese adipocytes exert a pro-inflammatory effect on airway epithelial cells, and these alterations are attenuated by diet-induced weight loss, which could have implications for the airway dysfunction related to obese asthma and its mitigation by weight loss.

scholarly journals Differential effect of weight loss with low-fat diet or high-fat diet restriction on inflammation in the liver and adipose tissue of mice with diet-induced obesity

2011 ◽  
Vol 219 (1) ◽  
pp. 100-108 ◽  
Author(s):  
Qun Wang ◽  
Xiaoyuan Dai Perrard ◽  
Jerry L. Perrard ◽  
Amir Mansoori ◽  
Joe L. Raya ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
High Fat Diet ◽  
Differential Effect ◽  
High Fat ◽  
Diet Restriction ◽  
Low Fat ◽  
Low Fat Diet ◽  
Diet Induced Obesity

scholarly journals Altered Gut Microbiota Is a Novel Mechanism for the Adverse Effects Induced by Foodborne Titanium Dioxide Nanoparticles in Obese and Non-obese Mice (P21-021-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Hengjun Du ◽  
Xiaoqiong Cao ◽  
Yanhui Han ◽  
Min Gu ◽  
Hang Xiao
Keyword(s):  
Titanium Dioxide ◽  
Adverse Effects ◽  
Gut Microbiota ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Low Fat ◽  
Colonic Inflammation ◽  
Tio2 Nps ◽  
Low Fat Diet

Abstract Objectives Many food products contain inorganic nanoparticles (NPs), such as titanium dioxide (TiO2) NPs. There is increasing concern about the potential unintended health risks associated with foodborne TiO2 NPs in certain populations, such as the obese. The purpose of this study was to determine the adverse effects of TiO2 NPs in obese individuals, the molecular mechanism involved and the potential role of gut microbiota in mediating the adverse effects. Methods Two types of TiO2 (30 nm and E171-Food grade TiO2) were mixed with mouse diet at 0.1 wt% and fed to two populations of mice (high-fat diet-fed obese mice and non-obese mice). Meanwhile, fecal samples from the above groups of mice were collected weekly for transplanting to four groups of mice fed a low-fat diet for 10 weeks. 16 s rRNA gene amplicon sequencing, histological analysis, immunohistochemistry, ELISA and SCFAs analysis were utilized to characterize the composition of the microbiota, inflammation status, and the effects of altered gut microbiota on the inflammation status of the mouse colon. Results TiO2 NPs significantly altered the composition of gut microbiota with stronger alterations in the high-fat diet-fed obese mice than the low-fat diet-fed non-obese mice. The abundance of inflammation-related cytokines (e.g., IL-10, IL-12p70, and IL-17) and myeloperoxidase (MPO) in the mouse colonic mucosa were significantly altered by TiO2 NPs to produce an inflammatory state. TiO2 NPs decreased the cecal levels of SCFAs such as butyrate. Moreover, the magnitude of the above alteration was higher in the obese mice than in the non-obese mice. After 10 weeks of microbial transplant, microbiota from the mice consuming a high-fat diet with TiO2 NPs led to an increase of pro-inflammatory cytokines, loss of healthy colonic morphology, and infiltration of immune cells in the colon of the low-fat diet-fed recipient mice, indicating a significant colonic inflammation. Conclusions TiO2 NPs altered gut microbiota in both obese and non-obese mice, with stronger effects in the obese mice, and the alteration of gut microbiota led to colonic inflammation in the mice. Overall, these findings provided a valuable new perspective on the potential adverse effects and appropriate mechanisms of foodborne TiO2 NPs among populations with different obese status. Funding Sources USDA/NIFA competitive grants to Hang Xiao.

scholarly journals Adiponectin and 8-epi-PGF2α as intermediate influence factors in weight reduction after legumes consumption: a 12-week randomized controlled trial

2020 ◽  
Author(s):  
Youngmin Han ◽  
Jong Ho Lee ◽  
Minjoo Kim
Keyword(s):  
Weight Loss ◽  
High Fat Diet ◽  
Diet Group ◽  
Controlled Study ◽  
High Fat ◽  
Low Fat ◽  
Carbohydrate Source ◽  
Randomized Controlled ◽  
Low Fat Diet ◽  
Obese Subjects

Abstract Background and Aims: The current nutritional intervention study was designed to determine the effect of legume on body weight in obese subjects. Methods Randomized controlled study of 12 weeks with 383 participants (body mass index ≥ 25 kg/m2) was enrolled for the study. The intervention program consisted of replacing 1/3 refined rice intake with legumes three times per day as a carbohydrate source in high fat diet group. In contrast, low fat diet group was recommended to eat as their usual diet. Results In high fat diet group, intake of energy and carbohydrate were lower, while the intake of fat and protein were higher. Mean weight loss at 12 weeks was 2.87 ± 0.21 kg and 0.17 ± 0.11 kg in the high fat diet group and low fat diet group, respectively, and was significantly different between groups (P < 0.001). HDL-cholesterol and adiponectin were increased, while glucose, insulin, triglyceride, HOMA-IR index, and 8-epi-PGF2α were decreased at 12 weeks in the high fat diet group compared with baseline. Conclusions The conclusion is that the consumption of legumes may accelerate weight loss accompanied by regulation of adiponectin and 8-epi-PGF2α in obese subjects. Also, increases in plasma adiponectin induced by a larger amount of weight loss may relate to greater activation of insulin resistance. Trial registrations: NCT04392882 (Registered 19 May 2020 - Retrospectively registered, https://clinicaltrials.gov/ct2/show/NCT04392882?cond=NCT04392882&draw=2&rank=1)

scholarly journals Overproduction of growth differentiation factor 15 promotes human rhinovirus infection and virus-induced inflammation in the lung

2018 ◽  
Vol 314 (3) ◽  
pp. L514-L527 ◽  
Author(s):  
Qun Wu ◽  
Di Jiang ◽  
Niccolette R. Schaefer ◽  
Laura Harmacek ◽  
Brian P. O’Connor ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Inflammatory Responses ◽  
Airway Epithelial Cells ◽  
Human Rhinovirus ◽  
Chronic Obstructive ◽  
Airway Epithelial ◽  
Growth Differentiation Factor 15 ◽  
Human Airway ◽  
Differentiation Factor ◽  
Human Airway Epithelial Cells

Human rhinovirus (HRV) is the most common virus contributing to acute exacerbations of chronic obstructive pulmonary disease (COPD) nearly year round, but the mechanisms have not been well elucidated. Recent clinical studies suggest that high levels of growth differentiation factor 15 (GDF15) protein in the blood are associated with an increased yearly rate of all-cause COPD exacerbations. Therefore, in the current study, we investigated whether GDF15 promotes HRV infection and virus-induced lung inflammation. We first examined the role of GDF15 in regulating host defense and HRV-induced inflammation using human GDF15 transgenic mice and cultured human GDF15 transgenic mouse tracheal epithelial cells. Next, we determined the effect of GDF15 on viral replication, antiviral responses, and inflammation in human airway epithelial cells with GDF15 knockdown and HRV infection. Finally, we explored the signaling pathways involved in airway epithelial responses to HRV infection in the context of GDF15. Human GDF15 protein overexpression in mice led to exaggerated inflammatory responses to HRV, increased infectious particle release, and decreased IFN-λ2/3 (IL-28A/B) mRNA expression in the lung. Moreover, GDF15 facilitated HRV replication and inflammation via inhibiting IFN-λ1/IL-29 protein production in human airway epithelial cells. Lastly, Smad1 cooperated with interferon regulatory factor 7 (IRF7) to regulate airway epithelial responses to HRV infection partly via GDF15 signaling. Our results reveal a novel function of GDF15 in promoting lung HRV infection and virus-induced inflammation, which may be a new mechanism for the increased susceptibility and severity of respiratory viral (i.e., HRV) infection in cigarette smoke-exposed airways with GDF15 overproduction.

Abstract 480: Exacerbation of Arterial Stiffness in Obese Adiponectin Deficient Mice

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Megha Murali ◽  
Carla Taylor ◽  
Peter Zahradka ◽  
Jeffrey Wigle
Keyword(s):  
Arterial Stiffness ◽  
Pulse Wave Velocity ◽  
Wave Velocity ◽  
High Fat Diet ◽  
Pulse Wave ◽  
High Fat ◽  
Low Fat ◽  
Low Fat Diet ◽  
High Fat Diets ◽  
Fat Diets

Background and Objective: Arterial stiffness is recognized as being an independent predictor of incipient vascular disease associated with obesity and metabolic syndrome. In obese subjects, the decrease in the plasma level of adiponectin, an anti-diabetic and anti-atherogenic adipokine, is well known. Hence the aim of our study was to examine the effect of loss of adiponectin on the development of arterial stiffness in response to a high fat diet. Methods and Results: Male 8-week old adiponectin knockout (APN KO) and C57BL/6 (control) mice were fed a high fat diet (60% Calories from fat) for 12 weeks to induce obesity and insulin resistance (n=10/group). APN KO and C57BL/6 mice were fed a low fat diet (10% Calories from fat) and used as lean controls (n=10/group). After 12 weeks on the high fat diet, the APN KO mice weighed significantly more than the C57BL/6 mice (45.1±1.3 g vs 40.1±1.1 g, p=0.0008) but there was no difference in the final weights between genotypes fed the low fat diet. APN KO mice on both high and low fat diets for 12 weeks developed insulin resistance as measured by oral glucose tolerance test (Area under curve (AUC) mmol/L х min = 437±70 and 438±57) as compared to the C57BL/6 mice fed low or high fat diets (AUC mmol/L х min = 251±27 and 245±43). Arterial stiffness was determined by Doppler pulse wave velocity analysis of the femoral artery. Pulse wave velocity was increased in APN KO mice fed a high fat diet relative to those fed the low fat diet (12.56±0.78 cm/s vs 9.47±0.95 cm/s, p=0.0035; n=8-10). Pulse wave velocity was not different between C57BL/6 control mice on the low or high fat diets (10.63±0.73 cm/s and 10.86±0.50 cm/s), thus revealing that only mice deficient in adiponectin developed arterial stiffness in response to high fat diet. Conclusions: Potentiation of the vascular stiffness in diet-induced obese APN KO mice indicates that adiponectin has a role in modulating vascular structure and the APN KO mouse models the vascular changes that occur in human obesity and metabolic disorders. Morphometric analysis of the aortic tissues for vessel thickness and expression of extracellular proteins will further validate the potential role of adiponectin on the maintenance of arterial elasticity in addition to its known effect on eNOS mediated vasoprotection.

scholarly journals Expression of eotaxin in 3T3-L1 adipocytes and the effects of weight loss in high-fat diet induced obese mice

2011 ◽  
Vol 5 (1) ◽  
pp. 11 ◽  
Author(s):  
Hyun-Jung Kim ◽  
Chang-Hyun Kim ◽  
Do-Hyun Lee ◽  
Min-Woo Han ◽  
Mi-Young Kim ◽  
...  
Keyword(s):  
Weight Loss ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat
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